Association of Depressed Mood With Herpes Simplex Virus-2 Immunoglobulin-G Levels in Pregnancy.

PubMed

Hsu, Pao-Chu; Yolken, Robert H; Postolache, Teodor T; Beckie, Theresa M; Munro, Cindy L; Groer, Maureen W

2016-10-01

Depressed mood is common in pregnancy, is associated with stress, and could result in immune suppression that may lead to latent herpes viral reactivation. This study investigated whether depressed mood is associated with higher herpes viral IgG levels in pregnant women. Complete cross-sectional data from 247 pregnant women were available for this substudy. The data included demographics, scores on the Perceived Stress Scale and Profile of Mood States (POMS), and a panel of serum IgG levels for human herpesviruses. Only the herpes simplex virus type 2 (HSV-2) (genital herpes) IgG level was associated with Perceived Stress Scale and POMS-Depression/Dejection (POMS-D) score. Hierarchical multiple regression analysis was used to examine the association of POMS-D with herpesviral IgG levels adjusting for demographic variables. In the final model, African American race (β = .251, p < .001), older age (β = .199, p = .002), single marital status (β = -.304, p < .001), and depressed mood (β = .122, p = .04) were associated with HSV-2 IgG levels. In logistic regression, the strongest correlates of HSV IgG positivity were single marital status, followed by POMS-D scores and African American race. Genital herpes is a concern in pregnancy. Antibody titers may indicate asymptomatic viral shedding, viral reactivation, or primary viral infection. Antibody levels may be higher because of the immune changes during pregnancy and potential immune effects of depressed mood causing reactivation of latent HSV-2.

The quantity and quality of α-gal-specific antibodies differ in individuals with and without delayed red meat allergy.

PubMed

Kollmann, D; Nagl, B; Ebner, C; Emminger, W; Wöhrl, S; Kitzmüller, C; Vrtala, S; Mangold, A; Ankersmit, H-J; Bohle, B

2017-02-01

IgG to galactose-α-1,3-galactose (α-gal) are highly abundant natural antibodies (Ab) in humans. α-Gal-specific IgE Ab cause a special form of meat allergy characterized by severe systemic reactions 3-7 h after consumption of red meat. We investigated 20 patients who experienced such reactions and characterized their α-gal-specific IgE and IgG responses in more detail. α-Gal-specific IgE was determined by ImmunoCAP. IgE reactivity to meat extract and bovine gamma globulin (BGG) was assessed by immunoblotting and ELISA, respectively. In some experiments, sera were pre-incubated with α-gal or protein G to deplete IgG Ab. α-Gal-specific IgG 1-4 Ab in individuals with and without meat allergy were assessed by ELISA. In immunoblots, BGG was the most frequently recognized meat protein. Binding of IgE and IgG to BGG was confirmed by ELISA and completely abolished after pre-incubation with α-gal. Neither the depletion of autologous α-gal-specific IgG Ab nor the addition of α-gal-specific IgG Ab from nonallergic individuals changed the IgE recognition of BGG of meat-allergic patients. Meat-allergic patients showed significantly higher α-gal-specific IgG1 and IgG3 Ab than nonallergic individuals, whereas the latter showed significantly higher levels of α-gal-specific IgG4 Ab. Patients with delayed meat allergy display IgE and IgG Ab that selectively recognize the α-gal epitope on BGG. Their enhanced α-gal-specific IgE levels are accompanied by high levels of α-gal-specific IgG1 devoid of IgE-blocking activity. This subclass distribution is atypical for food allergies and distinct from natural α-gal IgG responses in nonallergic individuals. © 2016 The Authors. Allergy Published by John Wiley & Sons Ltd.

Higher Anti-CMV IgG Concentrations are Associated with Worse Neurocognitive Performance During Suppressive Antiretroviral Therapy.

PubMed

Letendre, Scott; Bharti, Ajay; Perez-Valero, Ignacio; Hanson, Barbara; Franklin, Donald; Woods, Steven Paul; Gianella, Sara; de Oliveira, Michelli Faria; Heaton, Robert K; Grant, Igor; Landay, Alan L; Lurain, Nell

2018-03-01

To determine the association of CMV infection with neurocognitive performance in HIV+ adults. Cross-sectional, observational, exploratory study. Anti-CMV IgG concentrations in blood and CMV DNA copies in blood and cerebrospinal fluid (CSF) were measured in stored specimens of 80 HIV+ adults who were previously assessed with a standardized, comprehensive neurocognitive test battery. Thirty-eight were taking suppressive antiretroviral therapy (ART, HIV RNA ≤ 50 copies/mL) and 42 were not taking ART. A panel of 7 soluble biomarkers were also measured by immunoassay in CSF. Anti-CMV IgG concentrations ranged from 5.2 to 46.1 U/mL. CMV DNA was detected in 7 (8.8%) blood plasma but in none of the CSF specimens. Higher anti-CMV IgG levels were associated with older age (p=0.0017), lower nadir CD4+ T-cell count (p<0.001), AIDS (p<0.001), and higher soluble CD163 (p=0.009). Higher anti-CMV IgG levels trended toward an association with worse neurocognitive performance overall (p=0.059). This correlation was present in those taking suppressive ART (p=0.0049) but not in those who were not taking ART (p=0.92). Worse neurocognitive performance remained associated with higher anti-CMV IgG levels after accounting for other covariates in multivariate models (Model p=0.0038). Detectable plasma CMV DNA was associated with AIDS (p=0.05) but not with neurocognitive performance. CMV may influence neurocognitive performance in HIV+ adults taking suppressive ART. Future clinical trials of anti-CMV therapy should help determine whether the observed relationships are causal.

A small subgroup of Hashimoto's thyroiditis is associated with IgG4-related disease.

PubMed

Jokisch, Friedrich; Kleinlein, Irene; Haller, Bernhard; Seehaus, Tanja; Fuerst, Heinrich; Kremer, Marcus

2016-03-01

IgG4-related disease is a newly identified syndrome characterized by high serum IgG4 levels and increased IgG4-positive plasma cells in involved organs. The incidence of IgG4-related thyroiditis in the Caucasian population of Europe is unknown. We investigated formalin-fixed thyroid gland samples of 216 patients (191 Hashimoto's thyroiditis, 5 Riedel's thyroiditis, and 20 goiters, as controls), morphologically, and immunohistochemically. Cases were divided into two groups: IgG4-related Hashimoto's thyroiditis (24 cases) together with Riedel thyroiditis (1 case) and 171 non-IgG4-related thyroiditis. Compared to the non-IgG4-related cases, IgG4-related thyroiditis showed a higher IgG4/IgG ratio (0.6 vs. 0.1, p < 0.0001), a higher median IgG4 count (45.2 vs. 6.2, p < 0.0001), an association with younger age (42.1 vs. 48.1 years, p = 0.036), and a lower female-to-male ratio (11:1 vs. 17.5:1). Fibrous variant of Hashimoto's thyroiditis was diagnosed in 23 of the 24 IgG4-related cases (96 %) and in 13 of 167 (18 %, p > 0.001) non-IgG4-related cases. The single case of IgG4-related Riedel's thyroiditis also showed a higher median IgG4 plasma cell count (56.3 vs. 14.3) and a higher IgG4/IgG ratio (0.5 vs. 0.2) than the four cases of non-IgG4-related Riedel's thyroiditis. Our data suggests the incidence of IgG4-related disease (IgG4-RD) of the thyroid gland in Europe is considerably lower than that observed in other studies. A significant elevation of IgG4-positive plasma cells was only found in a small group of Hashimoto's thyroiditis and then accompanied by intense fibrosis, indicating an association with IgG4-RD. Morphologically, IgG4-RD of the thyroid gland differs from that in other organ systems, exhibiting a dense fibrosis without intense eosinophilia or obliterative phlebitis.

Utility of serum IgG, IgG4 and carbonic anhydrase II antibodies in distinguishing autoimmune pancreatitis from pancreatic cancer and chronic pancreatitis.

PubMed

Talar-Wojnarowska, Renata; Gąsiorowska, Anita; Olakowski, Marek; Dranka-Bojarowska, Daria; Lampe, Paweł; Śmigielski, Jacek; Kujawiak, Magdalena; Grzegorczyk, Janina; Małecka-Panas, Ewa

2014-09-01

Autoimmune pancreatitis (AIP) can mimic pancreatic cancer in its clinical presentation, imaging features and laboratory parameters. The aim of our study was to compare IgG, IgG4 and anti-CAIIAb serum levels in patients with AIP, pancreatic adenocarcinoma (PA) and chronic pancreatitis (CP) and to assess their clinical significance and utility in differential diagnosis of pancreatic diseases. The study included 124 patients: 45 with PA, 24 with AIP and 55 with CP. Peripheral venous blood samples were obtained from all analyzed patients at the time of hospital admission and total IgG, IgG4 and anti-CAIIAB serum levels were measured using ELISA tests. Serum levels of IgG, IgG4 and anti-CAIIAb were significantly higher in patients with AIP compared to PA and CP patients (p<0.001). In AIP patients the median IgG levels were 19.7 g/l, IgG4 levels - 301.9 mg/dl and anti-CAIIAb - 81.82 ng/ml, compared to 10.61 g/l, 123.2mg/dl and 28.6 ng/ml, respectively, in PA patients. IgG4 for the cut-off 210 mg/dl showed the best sensitivity and specificity (83.8% and 89.5%) in AIP diagnosis compared to IgG (69.3% and 87.3%, respectively) and anti-CAIIAb (45.3% and 74.3%). However, 16 (35.5%) patients with PA and 14 (25.4%) patients with CP had IgG4 levels greater than 140 mg/dl. Moreover, in 3 (6.67%) patients with pancreatic cancer those values were greater than 280 mg/dl. No patients with CP had IgG4 more than 280 mg/dl. IgG4 at cut-off 210 mg/dl showed the best sensitivity and specificity in AIP diagnosis compared to IgG and anti-CAIIAb, however elevations of serum IgG4 may be seen in subjects without AIP, including pancreatic cancer. Copyright © 2014 Medical University of Bialystok. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Chronic inflammatory demyelinating polyneuropathy (CIDP): change of serum IgG dimer levels during treatment with intravenous immunoglobulins.

PubMed

Ritter, Christian; Bobylev, Ilja; Lehmann, Helmar C

2015-08-14

Intravenous immunoglobulin (IVIg) is an effective treatment in chronic inflammatory demyelinating polyneuropathy (CIDP). In most patients, the optimal IVIg dose and regime is unknown. Polyvalent immunoglobulin (Ig) G form idiotypic/anti-idiotypic antibody pairs in serum and IVIg preparations. We determined IgG dimer levels before and after IVIg treatment in CIDP patients with the aim to explore their utility to serve as a surrogate marker for treatment response. IgG was purified from serum of five controls without treatment, as well as from serum of 16 CIDP patients, two patients with Miller Fisher syndrome (MFS), and one patient with myasthenia gravis before and after treatment with IVIg. IgG dimer levels were determined by size exclusion chromatography. IgG dimer formation was correlated with clinical response to IVIg treatment in CIDP. Re-monomerized IgG dimer fractions were analyzed for immunoreactivity against peripheral nerve tissue. IgG dimer levels were significantly higher in post- compared to pre-IVIg infusion samples. Low post-treatment IgG dimer levels in CIDP patients were associated with clinical worsening during IVIg treatment. Re-monomerized IgG dimer fractions from CIDP patients showed immunoreactivity against peripheral nerve tissue, whereas similarly treated samples from MFS patients showed immunoreactivity against GQ1b. Assessment of IgG dimer levels could be a novel approach to monitor CIDP patients during IVIg treatment, but further studies in larger cohorts are warranted to explore their utility to serve as a potential therapeutic biomarker for IVIg treatment response in CIDP.

Athletes with higher VO2max present reduced oxLDL after a marathon race

PubMed Central

Bachi, André L L; Sierra, Ana Paula R; Rios, Francisco J O; Gonçalves, Danieli A; Ghorayeb, Nabil; Abud, Ronaldo L; Victorino, Angélica B; dos Santos, Juliana M B; Kiss, Maria Augusta D P; Pithon-Curi, Tania C; Vaisberg, Mauro

2015-01-01

Background During a session of prolonged and exhaustive exercise, such as a marathon race, large quantities of free radicals are produced and can oxidise (ox) several molecules, such as low-density lipoprotein (LDL). To prevent oxidative damage, athletes present higher antioxidant levels. However, the effect of marathon running on the natural IgM or IgG anti-oxLDL autoantibodies is not understood. Thus, we investigated the effect of a marathon race on oxidative stress and the mechanisms of control of this stress. Methods Blood samples of 20 marathon runners were collected 24 hours before, immediately and 72 hours after a marathon race to evaluate: plasma lipid profile; serum levels of oxLDL and anti-oxLDL autoantibodies (IgM and IgG isotype) and total antioxidant capacity (TAC). Maximum oxygen uptake (VO2max) was also determined. Results Immediately after the race, oxLDL and TAC levels decreased in comparison to the basal levels; however, the IgM or IgG anti-oxLDL levels remain unchanged. Whereas no differences were observed in the IgM or IgG anti-oxLDL levels 72h after the marathon, the oxLDL and TAC levels returned to the basal values. Significant positive correlations were observed between oxLDL and LDL-cholesterol before, and 72h after the marathon. Significant negative correlations were observed between oxLDL and VO2max immediately after the marathon and 72 h later, as well as between oxLDL and TAC 72 h after the race. Conclusions Athletes with a higher VO2max and total antioxidant activity presented reduced LDL oxidation. The levels of IgM or IgG anti-oxLDL autoantibodies were not affected by running the marathon. PMID:27900109

Antibodies against recombinant heat shock proteins of 60 kDa from enterobacteria in the sera and synovial fluid of HLA-B27 positive ankylosing spondylitis patients.

PubMed

Domínguez-López, M L; Ortega-Ortega, Y; Manríquez-Raya, J C; Burgos-Vargas, R; Vega-López, A; García-Latorre, E

2009-01-01

To study the association of HLA-B27 with IgG antibodies to different enterobacterial HSP60s in patients with ankylosing spondylitis (AS). IgG antibodies to 60 kDa enterobacterial HSPs were determined by ELISA in paired samples of sera and synovial fluid from 21 HLA-B27+ ankylosing spondylitis (AS) patients; and in sera from 32 HLA-B27+ AS patients, 35 HLA-B27+ healthy relatives of AS patients, and 60 HLA-B27- healthy individuals with no family members with AS. HLA-B27+ patients and healthy individuals showed significantly higher IgG antibody levels to recombinant enterobacterial HSP60s than HLA-B27- healthy controls. The levels of anti-HSP60Sf and anti-HSP60Ec antibodies correlated with disease activity and anti-HSP60Ec antibodies with male gender. No association between enterobacterial HSP60 antibody levels and disease duration was observed. All groups had lower levels of IgG antibodies to rHSP60 from Streptococcus pyogenes (rHSP60 Spy). In paired samples of sera and synovial fluid from B27+ patients, IgG antibodies to enterobacterial HSP60s were detected, but in significantly higher levels in sera than in synovial fluid. The anti-rHSPSpy IgG response in these samples was lower and similar in the three groups. A correlation was found between HLA-B27 and the response to recombinat enterobacterial HSP60s. This response could be associated with disease activitir and gender in some proteins and the presence eof IgG antibodies to these proteins in synovial fluid could be associated with the inflammatory process and initiation of AS.

IgG sera levels against a subset of periodontopathogens and severity of disease in aggressive periodontitis patients: a cross-sectional study of selected pocket sites.

PubMed

Saraiva, Luciana; Rebeis, Estela S; Martins, Eder de S; Sekiguchi, Ricardo T; Ando-Suguimoto, Ellen S; Mafra, Carlos Eduardo S; Holzhausen, Marinella; Romito, Giuseppe A; Mayer, Marcia P A

2014-10-01

To evaluate the association among serum immunoglobulin G (IgG) responses to Aggregatibacter actinomycetemcomitans (Aa) serotypes a, b and c, Porphyromonas gingivalis (Pg), Tannerella forsythia (Tf) and clinical parameters in Aggressive Periodontitis (AP) subjects. Associations between periodontal pathogens and clinical and immunological parameters were also evaluated. Thirty-eight subjects diagnosed with generalized AP (GAP) and localized AP (LAP) were included. Ten healthy controls were also evaluated. Clinical parameters were assessed and percentages of subgingival levels of Aa, Pg and Tf (beyond bacterial load), were determined by quantitative real-time polymerase chain reaction. Serum IgG antibody levels against Aa, Pg and Tf were evaluated by enzyme-linked immunosorbent assay. Percentages of Aa, Pg and Tf were significantly higher in AP than in controls. The response to Aa serotype c was higher in LAP subjects than in controls. There were no differences in microbial composition or antibodies responses between GAP and LAP, except for IgG response to Tf. Pg levels were correlated with probing depth (PD), BoP and CAL in GAP but not in LAP subjects. Tf levels correlated with PD and CAL in GAP subjects. In GAP, the infection levels of Aa and Pg correlated with the corresponding IgG levels to Aa serotype c and Pg. Given the evidences that IgG response in AP patients correlated with bacterial infection level in GAP, but not in LAP, and that LAP patients lack a response to Tf, despite harbouring this species, our data suggest a difference in host immune defence between these two forms of aggressive periodontitis. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Specific IgG antibodies in sera in patients with penicillin allergy.

PubMed

Qiao, Hai-Ling; Gao, Na; Jia, Lin-Jing; Yang, Jing; Tian, Xin

2009-06-01

The role of IgG antibodies in inducing or modifying allergic reaction has not been sufficiently clarified. The objective of this investigation is to elucidate the relationship between IgG antibodies and penicillin allergy, between IgG and IgE antibodies in allergic patients. Enzyme-linked immunosorbent assay and Radioallergosorbent test were used to examine eight kinds of specific IgG and IgE antibodies, including major antigenic determinants: benzylpenicilloyl (BPO), ampicilloyl (APO), amoxicilloyl (AXO) and phenoxomethylpenicilloyl (PVO), and minor antigenic determinants: benzylpenicillanyl (BPA), ampicillanyl (APA), amoxicillanyl (AXA) and phenoxomethylpenicillany (PVA), in the sera of 249 patients with penicillin allergy. Except BPA-IgG, seven kinds of antigenic determinants IgG antibodies levels were significantly higher than that of control group (P < 0.05). Positive rates of specific IgG and IgE were 47.0 and 57.8%, while positive rate of IgE and IgG together was 77.9%. The positive rate of IgG antibodies to major antigenic determinants (42.2%) was significantly higher than that of minor antigenic determinants (8.8%) (P < 0.05). The positive rate of IgG antibodies of patients with typical clinical symptoms after penicillin administration when skin tests were negative was significantly higher than that of patients with positive skin test (P < 0.01). There were no differences between the IgG positive rates to three kinds of determinants and that of all of eight kinds. The study indicates that IgG may be important in penicillin allergy with negative skin test and IgG antibodies to major antigenic determinants probably play a more important role in the process of allergic reaction.

Abnormal IgG4 antibody response to aeroallergens in allergic patients.

PubMed

Jeannin, P; Delneste, Y; Tillie-Leblond, I; Wallaert, B; carlier, A; Pestel, J; Tonnel, A B

1994-01-01

Various studies have suggested the involvement of immunoglobulin G4 (IgG4) antibodies (Ab) in the physiopathology of allergic disorders. Recently, an abnormal IgG4 Ab production in response to immunization has been reported in some atopic patients. Thus, in order to evidence in allergic patients, a potential abnormal IgG4 Ab response to aeroallergens following natural exposure, we compared, in 34 patients sensitive to Dermatophagoides pteronyssinus and in 16 healthy subjects, the IgG4 Ab response to D. pteronyssinus, grass pollen and cat dander, using a solid-phase radioimmunoassay. Since some patients were also sensitive to grass pollen and/or to cat dander, we analyzed, in all patients, the IgG4 Ab responses both towards the allergen(s) they were sensitive to (sensitizing allergen) or not (unrelated allergen). The results showed that 90% of the patients produced levels of antisensitizing allergen(s) IgG4 Ab significantly higher than the controls; this IgG4 Ab response was correlated with the corresponding specific IgE Ab level. In addition, among these patients, around 40% presented high levels of IgG4 Ab to the unrelated allergen(s). Thus, in allergic patients, while specific IgE Ab define the nature of the sensitizing allergen, the presence of IgG4 Ab directed against various allergens seems in relation with an abnormal isotype regulation associated with atopic disorders.

Glycosylation of IgG B cell receptor (IgG BCR) in multiple myeloma: relationship between sialylation and the signal activity of IgG BCR.

PubMed

Ilić, Vesna; Milosević-Jovcić, Nadezda; Petrović, Sonja; Marković, Dragana; Stefanović, Gordana; Ristić, Tatjana

2008-05-01

Little is known about the glycosylation of the isotype switched B cell receptor (BCR) in multiple myeloma, and the way it might affect receptor function. In this work IgG BCRs isolated from the individual lysates of peripheral blood lymphocytes (PBL) of 32 patients with IgG multiple myeloma and healthy controls were investigated for the expression of sialic acid (SA), galactose (Gal) and N-acetylglucosamine (GlcNAc), the sugars known to specify the glycoforms of human serum IgG. The degree of glycosylation and signaling status of all 32 isolated myeloma IgG BCRs were correlated and compared with the glycosylation of the IgG paraproteins isolated from sera of the same patients. It was shown that BCR IgG in myeloma is more heavily sialylated when compared with normal controls, that the increased sialylation of IgG BCR is associated with higher levels of tyrosine phosphorylation (signaling activity) of the IgG BCR supramolecular complex and that BCR IgG and serum IgG paraprotein from the same patient differed in all cases in the levels of terminal sugar expression. The results suggest that the development of the malignant clone in MM from post-switch B cells expressing IgG BCR at their surfaces to plasma cells secreting IgG paraprotein may be followed by permanent glycosylation changes in the IgG molecules.

Demonstration of IgG Subclass (IgG1 and IgG3) in Immuno-Related Hemocytopenia.

PubMed

Shao, Yuanyuan; Qi, Xiao; Fu, Rong; Liu, Hui; Wang, Yihao; Ding, Shaoxue; Wang, Huaquan; Li, Lijuan; Shao, Zonghong

2018-06-01

Immuno-related hemocytopenia (IRH) is defined as idiopathic cytopenia of undetermined significance (ICUS) patients with autoantibodies. In our previous studies, we found that IgG1 levels were increased in IRH patients and might cause the destruction of hematopoietic cells. In this study, we analyzed IgG subclasses in 30 IRH patients (male:female = 13:17, median age 32 years, range 18 - 56), 15 IRH remission patients (IRH-R) (male:female = 6:9, median age 34, range 20 - 52) and 20 normal controls (male:female = 8:12, median age 27, range 24 - 36) by Cytometric Bead Array, Flow Cytometry and Immunohistochemical staining. Levels of IgG1/IgG3 in the bone marrow supernatant of IRH patents, as well as the proportion of CD5+ B lymphocytes and Th2 cells (CD3+CD8-IL-4+) were higher than those of IRH-R patients and normal controls, and IgG1 levels had a positive correlation with the proportion of Th2 cells. In IRH patients, IgG1 and IgG3 were positive on nucleated erythrocytes and granulocytes, which were negative in IRH-R patients and healthy controls and had inverse correlations with hematopoietic function. Using immunohistochemical staining, IgG1 were also detected on bone marrow biopsies of IRH patients. The results indicated that IgG1 and IgG3 autoantibodies in IRH patients might play a key role in the IRH pathogenesis and in the abnormal immune function of IRH patients.

Mumps outbreaks in a highly vaccinated population: Investigation of a neutralization titre against the current circulating wildtype genotype G5 mumps virus.

PubMed

Kenny, Lena; O'Kelly, Edwin; Connell, Jeff; De Gascun, Cillian; Hassan, Jaythoon

2016-01-01

Mumps outbreaks continue to occur globally, despite high levels of uptake of the mumps vaccine. In order to address immunity to the current circulating wildtype virus, we sought to determine a mumps G5 specific IgG quantitative value which correlates with genotype G5 specific neutralization ability in vitro. Sera from 199 individuals including controls and acute mumps cases were assessed for mumps specific IgG titres using five different enzyme immunoassays coated with antigen from different mumps virus strains. A subset of 66 sera was also assessed for in vitro neutralizing antibody against a contemporary circulating genotype G5 mumps virus. For all the different antigenic targets, mumps specific IgG titres were higher in patients following acute mumps infection compared to controls. In acute mumps infected patients, females showed significantly higher serum titres of anti-G5 IgG compared to males (p<0.05). Furthermore, control males did not show any change in G5 specific IgG with increasing age whereas females show a progressive rise in titre. Linear regression analysis revealed a significant association between the mumps G5 specific IgG levels in the EIA and the in vitro neutralization titres (r(2)=0.59). Specific IgG to the current circulating genotype G5 mumps strain showed significantly lower titres in males which supports our previous observation that there is a male gender bias in cases of acute mumps infection. Furthermore, in this preliminary study, the data indicate that genotype G5 specific IgG levels of >40 RU/ml are required for neutralization capability to be observed in vitro. Copyright © 2015 Elsevier B.V. All rights reserved.

Influence of a cocoa-enriched diet on specific immune response in ovalbumin-sensitized rats.

PubMed

Pérez-Berezo, Teresa; Ramiro-Puig, Emma; Pérez-Cano, Francisco J; Castellote, Cristina; Permanyer, Joan; Franch, Angels; Castell, Margarida

2009-03-01

Previous studies in young rats have reported the impact of 3 weeks of high cocoa intake on healthy immune status. The present article describes the effects of a longer-term cocoa-enriched diet (9 weeks) on the specific immune response to ovalbumin (OVA) in adult Wistar rats. At 4 weeks after immunization, control rats produced anti-OVA antibodies, which, according their amount and isotype, were arranged as follows: IgG1 > IgG2a > IgM > IgG2b > IgG2c. Both cocoa diets studied (4% and 10%) down-modulated OVA-specific antibody levels of IgG1 (main subclass associated with the Th2 immune response in rats), IgG2a, IgG2c and IgM isotypes. Conversely, cocoa-fed rats presented equal or higher levels of anti-OVA IgG2b antibodies (subclass linked to the Th1 response). Spleen and lymph node cells from OVA-immunized control and cocoa-fed animals proliferated similarly under OVA stimulation. However, spleen cells from cocoa-fed animals showed decreased interleukin-4 secretion (main Th2 cytokine), and lymph node cells from the same rats displayed higher interferon-gamma secretion (main Th1 cytokine). These changes were accompanied by a reduction in the number of anti-OVA IgG-secreting cells in spleen. In conclusion, cocoa diets induced attenuation of antibody synthesis that may be attributable to specific down-regulation of the Th2 immune response.

Salivary markers in patients with chronic renal failure.

PubMed

Pallos, Debora; Leão, Mariella V P; Togeiro, Fernanda C F B; Alegre, Larissa; Ricardo, Lucilene Hernandes; Perozini, Caroline; Ruivo, Gilson Fernandes

2015-12-01

Chronic renal failure (CRF) is a progressive loss of renal function over a period of months or years. The major function of the kidneys is the removal of metabolic waste products, electrolytes and water. When this function is impaired, systemic changes, oral complications and alterations in salivary composition may occur. This study aimed to compare the levels of immunological and inflammatory components in the saliva samples from patients that undergo to hemodialysis treatment (HD), without HD and control. This study evaluated IgA, IgG, C reactive protein (CRP) and nitric oxide (NO) in saliva samples from 119 patients, who were divided into the control group (C), chronic renal failure (CRF) patient group and CRF patients on hemodialysis treatment (HD) group. IgA and IgG levels were analyzed by ELISA. Nitric oxide levels were determined indirectly by the nitrite concentration using Griess reagent; CRP by agglutination tests; and total proteins, by Bradford assay. The HD group showed significantly higher levels of IgG, IgA and CRP compared with the control and CRF groups. The CRF group presented the same amounts of IgG, IgA and CRP as the C group but significantly higher levels of NO similar to the HD group. Renal disease, particularly hemodialysis treatment during renal disease, seems to alter salivary immunological and inflammatory components. Thus, analyzing the levels of IgA, IgG, NO and CRP in saliva may be beneficial for monitoring renal disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

Development of candidate combination vaccine for hepatitis E and hepatitis B: a liposome encapsulation approach.

PubMed

Shrivastava, Shubham; Lole, Kavita S; Tripathy, Anuradha S; Shaligram, Umesh S; Arankalle, Vidya A

2009-11-05

To reduce extra injections, cost and ensure better coverage, use of combination vaccines is preferable. An attempt was made to evaluate the encapsulation of hepatitis E virus neutralizing epitope (NE) region and hepatitis B virus surface antigen (HBsAg) in liposomes as DNAs, proteins and DNA+protein. Mice groups were immunized with different liposome-encapsulated formulations and monitored for anti-HEV and anti-HBs titres, IgG subtypes, antigen-specific lymphocyte proliferation and cytokine levels. The protective levels of anti-HBs and in vitro virus-binding capacity of anti-HEV antibodies were assessed. Liposome-encapsulated DNA either singly or in combination did not elicit antibody response. Anti-HEV and anti-HBs IgG titres of individual component of protein alone (Lipo-E-P/Lipo-B-P) or DNA+protein formulations (Lipo-E-DP/Lipo-B-DP) were comparable to respective titres in combination vaccine of protein (Lipo-BE-P) and DNA+protein formulations (Lipo-BE-DP). IgG1 levels were significantly higher in Lipo-BE-P group whereas, equivalent levels of IgG1 and IgG2a were observed in Lipo-BE-DP group against both components of the vaccine. Combination vaccine group showed mixed Th1/Th2 cytokine profile. Liposome entrapped NE and HBsAg in protein and DNA+protein formats induce excellent immune response to both the components and need to be evaluated in higher animals.

Effects of dietary CLA supplementation, parity and different concentrate levels before calving on immunoglobulin G1, G2 and M concentrations in dairy cows.

PubMed

Eger, Melanie; Horn, Jana; Hussen, Jamal; Schuberth, Hans-Joachim; Scharf, Maria; Meyer, Ulrich; Dänicke, Sven; Bostedt, Hartwig; Breves, Gerhard

2017-10-01

Peripartal dairy cows exhibit a higher susceptibility for infectious diseases, which might be linked to the negative energy balance occurring at the onset of lactation. A dietary supplementation of conjugated linoleic acids (CLA) may reduce milk fat yield and subsequently lower the energy deficit. The utilization of immunoglobulins (Ig) for colostrogenesis might impair humoral immunity in peripartal dairy cows; therefore this study investigated the effects of a CLA supplement, parity and different dietary energy levels on plasma and colostrum IgG1, IgG2 and IgM levels in dairy cows and their calves. Blood samples were collected from 64 cows from 21days before until 56days after parturition and colostrum samples for the first 3days of lactation. Plasma immunoglobulin concentrations of 19 calves were determined before colostrum uptake. Neither plasma IgG1, nor IgG2 levels were affected by CLA or dietary energy level. However, immunoglobulin levels were affected by parity. Heifers possessed the lowest IgG1 concentrations. IgG2 concentrations were highest in cows with 2 lactations prior to parturition and in heifers after parturition. Plasma IgM levels were characterized by a sharp decrease 3days prior to parturition and were scarcely affected by the feeding regimen or parity. Generally, immunoglobulin levels appear to be mostly independent from the peripartal energy balance of the cows and are not influenced by dietary CLA. However, pronounced differences among parities for IgG1 and IgG2 were revealed which should be further evaluated. Copyright © 2017 Elsevier Ltd. All rights reserved.

IgG4 anti-infliximab in treated patients: clinical impact and temporal evolution.

PubMed

Vultaggio, Alessandra; Nencini, Francesca; Carraresi, Alessia; Pratesi, Sara; Movérare, Robert; Eriksson, Camilla; Venemalm, Lennart; Maggi, Enrico; Matucci, Andrea

2018-05-02

Infliximab (IFX) carries potential risk of immunogenicity with the production of anti-drug antibodies (ADA). ADA may belong to different isotypes and are usually measured by ELISA bridging assay. This test is not designed to detect IgG4 antibodies. The aim was to measure IgG4 anti-IFX antibodies in a cohort of IFX-treated patients and to evaluate their relationship with ADA and their clinical impact. ADA were detected by using a bridging ELISA in the serum of 222 treated patients with different clinical outcomes to IFX. The same samples were analysed for IgG4 anti-IFX antibodies using an experimental ImmunoCAP assay with reduced serum IgG4 background levels. A longitudinal evaluation was performed in a subgroup of 38 patients to define the temporal evolution of IgG4 anti-IFX. IgG4 anti-IFX was found in 26.6% of patients. Eigthy out of 222 patients were ADA+ (36%) and the majority (57/80, 71.3%) had IgG4 anti-IFX. Two IgG4-positive but ADA-negative patients were identified. IgG4 anti-IFX levels correlated with the serum levels of ADA. IgG4 anti-IFX was more common in both reactive and non-responder patients than in tolerant/responder patients. Patients who had experienced IgE-mediated reactions displayed significantly higher IgG4 anti-IFX than IgE-negative reactive patients. The majority of patients tested positive for IgG4 anti-IFX after the first seven infusions. IgG4 anti-IFX is common in treated patients and a large part of ADA producing patients produce IgG4 antibodies. The IgG4 anti-IFX response does not prevent hypersensitivity reactions to IFX and correlates with the IgE anti-IFX response. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

IgG2 Antibodies against a Clinical Grade Plasmodium falciparum CSP Vaccine Antigen Associate with Protection against Transgenic Sporozoite Challenge in Mice

PubMed Central

Schwenk, Robert; Nikki, Jennifer; Rein, Lisa; Spaccapelo, Roberta; Crisanti, Andrea; Wightman, Paul D.; Ockenhouse, Christian F.; Dutta, Sheetij

2014-01-01

The availability of a highly purified and well characterized circumsporozoite protein (CSP) is essential to improve upon the partial success of recombinant CSP-based malaria vaccine candidates. Soluble, near full-length, Plasmodium falciparum CSP vaccine antigen (CS/D) was produced in E. coli under bio-production conditions that comply with current Good Manufacturing Practices (cGMP). A mouse immunogenicity study was conducted using a stable oil-in-water emulsion (SE) of CS/D in combination with the Toll-Like Receptor 4 (TLR4) agonist Glucopyranosyl Lipid A (GLA/SE), or one of two TLR7/8 agonists: R848 (un-conjugated) or 3M-051 (covalently conjugated). Compared to Alum and SE, GLA/SE induced higher CS/D specific antibody response in Balb/c mice. Subclass analysis showed higher IgG2:IgG1 ratio of GLA/SE induced antibodies as compared to Alum and SE. TLR synergy was not observed when soluble R848 was mixed with GLA/SE. Antibody response of 3M051 formulations in Balb/c was similar to GLA/SE, except for the higher IgG2:IgG1 ratio and a trend towards higher T cell responses in 3M051 containing groups. However, no synergistic enhancement of antibody and T cell response was evident when 3M051 conjugate was mixed with GLA/SE. In C57Bl/6 mice, CS/D adjuvanted with 3M051/SE or GLA/SE induced higher CSP repeat specific titers compared to SE. While, 3M051 induced antibodies had high IgG2c:IgG1 ratio, GLA/SE promoted high levels of both IgG1 and IgG2c. GLA/SE also induced more potent T-cell responses compared to SE in two independent C57/BL6 vaccination studies, suggesting a balanced and productive TH1/TH2 response. GLA and 3M-051 similarly enhanced the protective efficacy of CS/D against challenge with a transgenic P. berghei parasite and most importantly, high levels of cytophilic IgG2 antibodies were associated with protection in this model. Our data indicated that the cGMP-grade, soluble CS/D antigen combined with the TLR4-containing adjuvant GLA/SE warrants further evaluation for protective responses in humans. PMID:25343487

Abnormally high levels of anti-collagen type IV IgG antibodies in the serum of patients with a clinically isolated syndrome correlate with an increased risk of conversion to MS.

PubMed

Sadarzanska-Terzieva, Behidhe; Tzvetanov, Plamen; Hegde, Vishwajit; Al-Hashel, Jasem Y; Rousseff, Rossen Т; Haralanov, Lubomir; Stamenov, Boyko; Atanassova, Milena; Marinova, Iveta; Marinova, Anna; Rousseva, Adelaida

2015-06-01

To investigate anti-collagen-type-IV serum antibodies (ACIVAbs) levels in patients with clinically isolated syndrome (CIS), and to determine their predictive value for conversion into multiple sclerosis (MS). Serum levels of IgM and IgG ACIVAbs in 40 untreated patients with CIS (13 male, mean age 34.85±11.4 years, range 16-58 years) were compared to those of 27 gender- and age-matched healthy controls. ACIVAbs were quantified using ELISA. Patients were followed for 5 years by clinical examination and MRI studies. Thirty two patients (80%) converted to MS (converted CIS, C-CIS group) while the rest 8 (20%) did not (non-converted CIS, NC-CIS). The C-CIS patients had significantly higher levels of IgG ACIVAb compared to NC-CIS while the IgM levels did not differ between C-CIS and NC-CIS. Conversion to MS occurred in 66% of patients with IgG ACIVAbs levels exceeding the 95th percentile found in controls. IgG ACIVAbs levels correlated positively with the serum levels of matrix metalloproteinases type 9 (r = 0.37; p = 0.003) and inversely with those of tissue inhibitor of metalloproteinases type 1 (r = -0.43; p = 0.0008). High serum levels of IgG ACIVAbs in patients with CIS correlate strongly with increased risk of conversion to MS. Copyright © 2015 Elsevier B.V. All rights reserved.

Comparison of two commercial vaccines against visceral leishmaniasis in dogs from endemic areas: IgG, and subclasses, parasitism, and parasite transmission by xenodiagnosis.

PubMed

Fernandes, Consuelo Barreto; Junior, Jairo Torres Magalhães; de Jesus, Clauceane; Souza, Bárbara Maria Paraná da Silva; Larangeira, Daniela Farias; Fraga, Deborah Bittencourt Mothé; Tavares Veras, Patricia Sampaio; Barrouin-Melo, Stella Maria

2014-03-05

The incidence of zoonotic canine visceral leishmaniasis (CVL) would decrease if dogs were effectively vaccinated; however, additional data on the efficacy of canine vaccines are required for their approved preventative use. To prospectively evaluate vaccination outcomes using two products commercially available in Brazil, with respect to adverse reactions (reactogenicity), humoral response, disease signs, parasitism, and parasite infectiousness in naturally exposed pet dogs in an endemic area of visceral leishmaniasis (VL). From 2010 to 2012, healthy dogs were vaccinated with Leishmune(®) (50 animals) or Leish-Tec(®) (50 animals). Each dog was examined to identify clinical signs during peri- and post-vaccination procedures every 2 months for 11 months to identify the presence of parasites or parasite DNA in splenic samples using culturing or PCR, respectively. Levels of anti-Leishmania IgG, IgG1, and IgG2 were quantified in sera by ELISA and infectiousness was assessed by xenodiagnosis. Adverse effects occurred in 2.2% (1/45) and 13.0% (6/46) of the animals in the Leishmune(®) and Leish-Tec(®) groups, respectively. IgG levels peaked on the 21st day following the first dose of Leishmune(®) and on the 21st day after the second dose of Leish-Tec(®). The final seropositivity rate for IgG was 32.5% (13/40) and 30.9% (13/42) in the Leishmune(®) and Leish-Tec(®) groups, respectively. The Leishmune(®) group presented higher levels of IgG1 and IgG2 compared to the Leish-Tec(®) group (p<0.001), and ELISA reactivity in both vaccinated groups was significantly lower (p<0.001) than in infected positive control dogs. Parasitism was observed in 12.2% (5/41) of the Leishmune(®) group, and 7.9% (3/38) of the Leish-Tec(®) group, with xenodiagnostic transmission rates of Leishmania to Lutzomyia longipalpis of 5.1% (2/39), and 5.4% (2/37), respectively. No significant differences were observed in dogs vaccinated with Leishmune(®) or Leish-Tec(®), with respect to LVC clinical aspects, parasitism, IgG seropositivity, or dog infectiousness. The Leishmune(®)-vaccinated animals presented higher levels of IgG, IgG1, and IgG2. The animals vaccinated with Leish-Tec(®) exhibited adverse reactions with greater frequency and severity. Copyright © 2013 Elsevier Ltd. All rights reserved.

Th17-Related Cytokines in Systemic Lupus Erythematosus Patients with Dilated Cardiomyopathies: A Possible Linkage to Parvovirus B19 Infection

PubMed Central

Chen, Der-Yuan; Chen, Yi-Ming; Lan, Joung-Liang

2014-01-01

Dilated cardiomyopathies (DCM) are a major cause of mortality in patients with systemic lupus erythematosus (SLE). Immune responses induced by human parvovirus B19 (B19) are considered an important pathogenic mechanism in myocarditis or DCM. However, little is known about Th17-related cytokines in SLE patients with DCM about the linkage with B19 infection. IgM and IgG against B19 viral protein, and serum levels of Th17-related cytokines were determined using ELISA in eight SLE patients with DCM and six patients with valvular heart disease (VHD). Humoral responses of anti-B19-VP1u and anti-B19-NS1 antibody were assessed using Western blot and B19 DNA was detected by nested Polymerase Chain Reaction (PCR). Levels of interleukin (IL)-17, IL-6, IL-1β, and tumor necrosis factor (TNF)-α were significantly higher in SLE patients with DCM (mean ± SEM, 390.99±125.48 pg/ml, 370.24±114.09 pg/ml, 36.01±16.90 pg/ml, and 183.84±82.94 pg/ml, respectively) compared to healthy controls (51.32±3.04 pg/ml, p<0.001; 36.88±6.64 pg/ml, p<0.001; 5.39±0.62 pg/ml, p<0.005; and 82.13±2.42 pg/ml, p<0.005, respectively). Levels of IL-17 and IL-6 were higher in SLE patients with DCM versus those with VHD (both p<0.01). Five (62.5%) of DCM patients had detectable anti-B19-NS1 IgG and four (50.0%) of them had anti-B19-VP1u IgG, whereas only one (16.7%) of VHD patients had detectable anti-B19-NS1 IgG and anti-B19-VP1u IgG. Serum levels of IL-17, IL-6 and IL-1β were markedly higher in SLE patients with anti-B19-VP1u IgG and anti-B19-NS1 IgG compared to those without anti-B19-VP1u IgG or anti-B19-NS1 IgG, respectively. These suggest a potential association of B19 with DCM and Th17-related cytokines implicated in the pathogenesis of DCM in SLE patients. PMID:25462010

Clinical, parasitological and immunological features of canal cleaners hyper-exposed to Schistosoma mansoni in the Sudan

PubMed Central

SATTI, M Z; SULAIMAN, S M; HOMEIDA, M M A; YOUNIS, S A; GHALIB, H W

1996-01-01

The present work was a longitudinal study on Schistosoma mansoni infection in occupationally hyperexposed canal cleaners in the Sudan and the influence of therapy on the parasitological and humoral immune parameters. Chronically infected canal cleaners (n = 28) were more resistant to reinfection (Fisher's exact test, P < 0.05) than newly recruited canal cleaners (n = 17). Chronically infected canal cleaners had a significantly higher degree of Symmers' fibrosis (χ2 = 19.1, P < 0.0001), significantly larger portal vein diameter (P < 0.05) and enlarged spleen (χ2 = 4.2, P < 0.05) than recently infected, newly recruited canal cleaners. ELISA was used to detect IgG, IgA and IgM in response to whole worm homogenate (WWH) and cercarial homogenate (CH). Chronically infected canal cleaners had significantly higher IgG to WWH antigen than newly recruited canal cleaners and normally exposed individuals (P < 0.05), while both chronically infected and newly recruited canal cleaners had higher IgG levels to CH antigen than normally exposed individuals (P < 0.05). The newly recruited canal cleaners had a significantly higher IgM level to CH antigen than chronically infected canal cleaners (P < 0.05). The IgG level to WWH antigen increased significantly after treatment in newly recruited canal cleaners and normally exposed individuals (P < 0.05). The IgA level to CH antigen increased significantly after treatment in the chronically infected group (P < 0.05). Comparison of the serological parameters between the different study groups with regards to infection and treatment is discussed. PMID:9099926

Vaccine potential of recombinant cathepsin B against Fasciola gigantica.

PubMed

Chantree, Pathanin; Phatsara, Manussabhorn; Meemon, Krai; Chaichanasak, Pannigan; Changklungmoa, Narin; Kueakhai, Pornanan; Lorsuwannarat, Natcha; Sangpairoj, Kant; Songkoomkrong, Sineenart; Wanichanon, Chaitip; Itagaki, Tadashi; Sobhon, Prasert

2013-09-01

In Fasciola gigantica, cathepsin Bs, especially cathepsin B2 and B3 are expressed in early juvenile stages, and are proposed to mediate the invasion of host tissues. Thus they are thought to be the target vaccine candidates that can block the invasion and migration of the juvenile parasite. To evaluate their vaccine potential, the recombinant cathepsin B2 (rFgCatB2) and cathepsin B3 (rFgCatB3) were expressed in yeast, Pichia pastoris, and used to immunize mice in combination with Freund's adjuvant to evaluate the protection against the infection by F. gigantica metacercariae, and the induction of immune responses. Mice immunized with both recombinant proteins exhibited high percent of parasite reduction at 60% for rFgCatB2 and 66% for rFgCatB3. Immunization by both antigens induced continuously increasing levels of IgG1 and IgG2a with a higher level of IgG1 isotype, indicating the mixed Th1/Th2 responses with Th2 predominating. When examined individually, the higher levels of IgG1 and IgG2a were correlated with the lower numbers of worm recoveries. Thus, both cathepsin B2 and cathepsin B3 are plausible vaccine candidates whose potential should be further tested in large economic animals. Copyright © 2013 Elsevier Inc. All rights reserved.

Chronic cat allergen exposure induces a TH2 cell-dependent IgG4 response related to low sensitization.

PubMed

Renand, Amedee; Archila, Luis D; McGinty, John; Wambre, Erik; Robinson, David; Hales, Belinda J; Thomas, Wayne R; Kwok, William W

2015-12-01

In human subjects, allergen tolerance has been observed after high-dose allergen exposure or after completed allergen immunotherapy, which is related to the accumulation of anti-inflammatory IgG4. However, the specific T-cell response that leads to IgG4 induction during chronic allergen exposure remains poorly understood. We sought to evaluate the relationship between cat allergen-specific T-cell frequency, cat allergen-specific IgE and IgG4 titers, and clinical status in adults with cat allergy with and without cat ownership and the cellular mechanism by which IgG4 is produced. Fel d 1-, Fel d 4-, Fel d 7-, and Fel d 8-specific T-cell responses were characterized by CD154 expression after antigen stimulation. In allergic subjects without cat ownership, the frequency of cat allergen (Fel d 1 and Fel d 4)-specific TH2 (sTH2) cells correlates with higher IgE levels and is linked to asthma. Paradoxically, we observed that subjects with cat allergy and chronic cat exposure maintain a high frequency of sTH2 cells, which correlates with higher IgG4 levels and low sensitization. B cells from allergic, but not nonallergic subjects, are able to produce IgG4 after cognate interactions with sTH2 clones and Fel d 1 peptide or the Fel d 1 recombinant protein. These experiments suggest that (1) allergen-experienced B cells with the capacity to produce IgG4 are present in allergic subjects and (2) cat allergen exposure induces an IgG4 response in a TH2 cell-dependent manner. Thus IgG4 accumulation could be mediated by chronic activation of the TH2 response, which in turn drives desensitization. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. All rights reserved.

The significance of specific IgG4 antibodies to methyltetrahydrophthalic anhydride in occupationally exposed subjects.

PubMed

Yokota, K; Yamaguchi, K; Takeshita, T; Morimoto, K

1998-06-01

A definitive role for allergen-specific IgG4 as either an anaphylactic or a blocking antibody, or both, remains controversial. A population of 148 workers from two condenser plants (A and B) using epoxy resin with methyltetrahydrophthalic anhydride (MTHPA) was studied to evaluate the significance of MTHPA-specific IgG4 antibody. The workers were evaluated through questionnaire and serological investigations. Ninety-seven (66%) of the currently exposed workers had positive MTHPA-specific IgE. IgE-sensitized workers in each plant had significantly more eye and nose complaints than unsensitized workers (P < 0.03). As the result of multiple logistic analysis, specific IgE antibodies was the most important predictor of work-related symptoms and its effect was greater than that of specific IgG4 (odds ratio 16.7 and 3.68, respectively). These indicate an IgE-mediated mechanism in most cases of work-related symptoms associated with MTHPA exposure. However, it cannot be denied that specific IgG4 is an anaphylactic antibody. Furthermore, IgE-sensitized workers in these plants displayed work-related symptoms despite the presence of specific IgG4. The frequency of positive specific IgG4 in continuously exposed workers was significantly (P < 0.02) higher in plant A than in plant B, reflecting the difference of the MTHPA levels between the two plants. In plant A, the frequency of positive specific IgG4 was significantly (P < 0.002) higher in continuously exposed workers than in intermittently exposed workers. Multiple regression analysis also confirmed that plant and exposure style contributed significantly (P < 0.01) to the determination of specific IgG4 levels. These results suggest that work-related eye and nasal symptoms are likely to be IgE-mediated, and that specific IgG4 may reflect the intensity of MTHPA exposure and may not act as a blocking antibody.

IgG antibodies to synthetic GPI are biomarkers of immune-status to both Plasmodium falciparum and Plasmodium vivax malaria in young children.

PubMed

França, Camila T; Li Wai Suen, Connie S N; Carmagnac, Amandine; Lin, Enmoore; Kiniboro, Benson; Siba, Peter; Schofield, Louis; Mueller, Ivo

2017-09-25

Further reduction in malaria prevalence and its eventual elimination would be greatly facilitated by the development of biomarkers of exposure and/or acquired immunity to malaria, as well as the deployment of effective vaccines against Plasmodium falciparum and Plasmodium vivax. A better understanding of the acquisition of immunity in naturally-exposed populations is essential for the identification of antigens useful as biomarkers, as well as to inform rational vaccine development. ELISA was used to measure total IgG to a synthetic form of glycosylphosphatidylinositol from P. falciparum (PfGPI) in a cohort of 1-3 years old Papua New Guinea children with well-characterized individual differences in exposure to P. falciparum and P. vivax blood-stage infections. The relationship between IgG levels to PfGPI and measures of recent and past exposure to P. falciparum and P. vivax infections was investigated, as well as the association between antibody levels and prospective risk of clinical malaria over 16 months of follow-up. Total IgG levels to PfGPI were low in the young children tested. Antibody levels were higher in the presence of P. falciparum or P. vivax infections, but short-lived. High IgG levels were associated with higher risk of P. falciparum malaria (IRR 1.33-1.66, P = 0.008-0.027), suggesting that they are biomarkers of increased exposure to P. falciparum infections. Given the cross-reactive nature of antibodies to PfGPI, high IgG levels were also associated with reduced risk of P. vivax malaria (IRR 0.65-0.67, P = 0.039-0.044), indicating that these antibodies are also markers of acquired immunity to P. vivax. This study highlights that in young children, IgG to PfGPI might be a useful marker of immune-status to both P. falciparum and P. vivax infections, and potentially useful to help malaria control programs to identify populations at-risk. Further functional studies are necessary to confirm the potential of PfGPI as a target for vaccine development.

Relation between IgG antibodies to foods and IgE antibodies to milk, egg, cat, dog and/or mite in a cross-sectional study.

PubMed

Eysink, P E; De Jong, M H; Bindels, P J; Scharp-Van Der Linden, V T; De Groot, C J; Stapel, S O; Aalberse, R C

1999-05-01

Because IgG antibodies to foods can be detected before IgE antibodies to inhalants, increased levels of IgG antibodies to foods might be used as a predictor of IgE-mediated allergy in initially nonatopic children. To examine the cross-sectional relation between IgG to foods (i.e. mixture of wheat and rice, mixture of soybean and peanut, egg white, cow's milk, meat, orange and potato) and specific IgE to cat, dog, mite, milk and egg white in 1-year-old children. All atopic children (n = 120; 58 with and 62 without eczema) and a random sample of the nonatopic children (n = 144) of the Bokaal study were tested on their IgG response to foods. The IgG results of the food assays were dichotomized high or low using the 66th centile as a cut-off value. Atopic children more often had high IgG levels to foods than nonatopic children. IgG to egg white (OR = 7.50) and mixture of wheat and rice (OR = 4.79) were most strongly associated with positive specific IgE. In a stepwise logistic regression analysis egg white, mixture of wheat and rice, and orange were selected (OR = 3.76, OR = 2.43, and OR = 2.11, respectively). In children without eczema higher levels of IgG to foods were still significantly associated with atopy, which was most prominent for egg white, orange and cow's milk. An increased IgG antibody level to foods, especially to egg white, orange, and mixture of wheat and rice, indicates an increased risk of having IgE to cat, dog, mite, egg and/or milk allergens, even in the noneczematous group. Therefore, in another prospective study we are currently investigating the usefulness of IgG in early identification, i.e. before IgE antibodies can be detected, of children with an increased risk of developing allergic diseases in the future.

Diagnostic Performance of Serum IgG4 Levels in Patients With IgG4-Related Disease

PubMed Central

Yu, Kuang-Hui; Chan, Tien-Ming; Tsai, Ping-Han; Chen, Ching-Hui; Chang, Pi-Yueh

2015-01-01

Abstract The aim of this study is to study the clinical features and diagnostic performance of IgG4 in Chinese populations with IgG4-related diseases (IgG4-RDs). The medical records of 2901 adult subjects who underwent serum IgG4 level tests conducted between December 2007 and May 2014 were reviewed. Serum concentrations of IgG4 were measured in 2901 cases, including 161 (5.6%) patients with IgG4-RD and 2740 (94.4%) patients without IgG4-RD (non-IgG4-RD group). The mean age of the IgG4-RD patients was 58.4 ± 16.1 years (range: 21–87), and 48 (29.8%) were women. The mean serum IgG4 level was significantly much higher in IgG4-RD patients than in non-IgG4-RD (1062.6 vs 104.3 mg/dL, P < 0.001) participants. For IgG4 >135 mg/dL, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), likelihood ratio (LR)+, and LR− were 86%, 77%, 18%, 99%, 3.70, and 0.19, respectively. When the upper limit of normal was doubled for an IgG4 >270 mg/dL, the corresponding data were 75%, 94%, 43%, 98%, 12.79, and 0.26, respectively. For IgG4 >405 mg/dL (tripling the upper limit of normal), the corresponding data were 62%, 98%, 68%, 98%, 37.00, and 0.39, respectively. When calculated according to the manufacturer's package insert cutoff (>201 mg/dL) for the diagnosis of IgG4-RD, the corresponding sensitivity, specificity, PPV, NPV, LR+, and LR− were 80%, 89%, 29%, 99%, 7.00, and 0.23, respectively. For IgG4 >402 mg/dL (>2× the upper limit of the normal range), the corresponding data were 62%, 98%, 68%, 98%, 36.21, and 0.39, respectively. For IgG4 >603 mg/dL (>3× the upper limit of the normal range), the corresponding data were 50%, 99%, 84%, 97%, 90.77 and 0.51, respectively. The optimal cutoff value of serum IgG4 (measured by nephelometry using a Siemens BN ProSpec instrument and Siemens reagent) for the diagnosis of IgG4-RD was 248 mg/dL, the sensitivity and specificity were 77.6% and 92.8%, respectively. The present study demonstrated that 2 or 3 times the upper limit of the manufacturer's reference range of the IgG4 level was a useful marker for the diagnosis of various types of IgG4-RD and the optimal cutoff level was 248 mg/dL. PMID:26469909

Increased Levels of Circulating Anti-ANXA1 IgG Antibody in Patients with Non-Small Cell Lung Cancer.

PubMed

Liang, Tingting; Han, Zhifeng; Zhao, Huan; Zhang, Xuan; Wang, Yao

2018-06-01

Our previous studies revealed that concentrations of circulating antibodies to annexin A1 (ANXA1) were increased in non-small lung cancer (NSCLC). This study was thus designed to replicate this initial finding with an independent sample set. An enzyme-linked immunosorbent assay (ELISA) was developed in-house to examine plasma antiANXA1 IgG levels in 220 patients with NSCLC and 200 control subjects. Mann-Whitney U test showed that patients with NSCLC had significantly higher anti-ANXA1 IgG levels than control subjects (Z = -4.02, p < 0.001); male patients appeared to mainly contribute to the increased antibody level (Z = -3.09, p = 0.002). Receiver operating characteristic (ROC) curve analysis showed an overall area under the ROC curve (AUC) of 0.61 (95% CI: 0.56 - 0.67), with sensitivity of 8% against a specificity of 95.0%. Spearman's correlation analysis failed to show a significant correlation between the anti-ANXA1 IgG levels and the expression of three tumor-associated antigens including p53 (r = 0.156, p = 0.027), Ki67 (r = -0.048, p = 0.489), and EGFR (r = 0.02, p = 0.782). Increased levels of circulating anti-ANXA1 IgG antibody may have a prognostic value for NSCLC.

Inverse relationship between toxic shock syndrome toxin-1 antibodies and interferon-γ and interleukin-6 in peripheral blood mononuclear cells from patients with pediatric tonsillitis caused by Staphylococcus aureus.

PubMed

Chen, Yinshuang; Huang, Yanmei; Liang, Bingshao; Dong, Hui; Yao, Shuwen; Xie, Yongqiang; Long, Yan; Zhong, Huamin; Yang, Yiyu; Zhu, Bing; Gong, Sitang; Zhou, Zhenwen

2017-06-01

Pediatric tonsillitis is frequently caused by Staphylococcus aureus, which is the most common pathogen that causes serious pyogenic infections in humans and endangers human health. S. aureus produces numerous potent virulence factors that play a critical role in the pathogenesis of the infection caused by this bacterium, and one of the most important toxins produced by S. aureus is toxic shock syndrome toxin-1 (TSST-1). The aim of this study is to investigate the first time the levels of IFN-γ and interleukin IL-6 in TSST-1-stimulated PBMCs from pediatric tonsillitis patients and the correlation of these cytokine levels with TSST-1-specific IgG in serum. TSST-1 gene of S. aureus was cloned and expressed in a prokaryotic expression system, and purified recombinant TSST-1 protein was used for measuring TSST-1-specific antibodies in the serum of patients with pediatric tonsillitis caused by S. aureus. Moreover, the levels of interferon (IFN)-γ and interleukin (IL)-6 in TSST-1-stimulated peripheral blood mononuclear cells (PBMCs) from pediatric tonsillitis patients were investigated. In patients with pediatric tonsillitis caused by S. aureus, significantly higher levels of serum TSST-1-specific IgG (P < 0.05) and IgG1 (P < 0.05) were detected than in healthy children. Moreover, PBMCs from the patients exhibited higher IFN-γ (P < 0.05) production in response to TSST-1 than did PBMCs from healthy children. In patients with pediatric tonsillitis caused by S. aureus, the positive rate of TSST-1-specific IgG was 70%, and the patients who tested negative for TSST-1-specific IgG exhibited significantly higher levels of IFN-γ (P < 0.05) and IL-6 (P < 0.05) than did the IgG-positive patients, in accord, the levels of TSST-1-specific IgG correlated inversely with the levels of IFN-γ and IL-6 in patients PBMCs stimulated with TSST-1. TSST-1 induces humoral and cellular immunity in pediatric tonsillitis caused by S. aureus, which suggests that TSST-1 may play an important role in the pathogenesis of pediatric tonsillitis. Copyright © 2017. Published by Elsevier B.V.

Increased levels of galactose-deficient IgG in sera of HIV-1-infected individuals.

PubMed

Moore, Jennifer S; Wu, Xueling; Kulhavy, Rose; Tomana, Milan; Novak, Jan; Moldoveanu, Zina; Brown, Rhubell; Goepfert, Paul A; Mestecky, Jiri

2005-03-04

The IgG from sera of patients with chronic inflammatory diseases of autoimmune character or some chronic microbial infections is frequently deficient in galactose on N-linked glycans. However, this phenomenon has not been investigated at length in human viral infections. To evaluate the glycosylation of serum IgG in HIV-1-positive patients. Psathyrella velutina lectin was used in enzyme-linked immunosorbent and Western blot assays to determine glycosylation. In addition, gas-liquid chromatography and mass spectrometry were utilized to confirm the galactose deficiency observed in the lectin-binding assays. HIV-1-infected individuals had significantly higher levels of galactose-deficient IgG than healthy controls. In fact, the galactose deficiency of the N-linked glycans observed in other diseases was even more profound in HIV-1 infection. This deficiency was primarily restricted to IgG when total serum glycoproteins were evaluated and IgG1 was the subclass most affected in all patients. Also, a significant increase in lectin binding was observed on IgG2 and IgG4 from HIV-1-positive females compared with HIV-1-negative females. Identification of deficient galactosylation of serum IgG from HIV-1-infected patients extended the spectrum of diseases in which this phenomenon has been observed. In addition, the results suggest yet another aspect of immune dysfunction as a result of HIV-1 infection.

Aggravation of Helicobacter pylori stomach infections in stressed military recruits.

PubMed

Jia, Keran; An, Liyun; Wang, Fukun; Shi, Lanchun; Ran, Xiangyang; Wang, Xianling; He, Zhanguo; Chen, Jing

2016-04-01

To investigate the effect of military stress on immune response and Helicobacter pylori stomach infections. In this prospective, observational study, the Symptom Checklist-90 questionnaire was completed by military recruits before and following a 3-month basic training programme. H. pylori immunoglobulin (Ig)G levels, C(14)-urea breath-test values and levels of cortisol, catecholamine, and certain humoral and cellular immune responses were measured before and after the basic training. For 60 military recruits, somatization, depression and paranoid ideation scores were significantly increased after, compared with before, basic training. Post-training H. pylori IgG detection revealed three additional cases of H. pylori infection. Post-training C(14)-urea breath-test values were significantly higher compared with before training - thus suggesting higher levels of H. pylori colonization in the stomach. Post-training cortisol and catecholamine levels were increased, while serum IgG levels were decreased; complement component (C)3 and C4 levels remained unchanged. Post-training CD4(+) and CD8(+) T-cell percentages and the CD4(+)/CD8(+) ratio were significantly reduced compared with before training. Serum interleukin (IL)-2 levels were lower and IL-10 levels were higher following training and there was a significant decrease in the IL-2/IL-10 ratio. Military stress may reduce humoral and cellular immune responses and may aggravate the severity of H. pylori infection. © The Author(s) 2016.

Aggravation of Helicobacter pylori stomach infections in stressed military recruits

PubMed Central

Jia, Keran; An, Liyun; Shi, Lanchun; Ran, Xiangyang; Wang, Xianling; He, Zhanguo; Chen, Jing

2016-01-01

Objective To investigate the effect of military stress on immune response and Helicobacter pylori stomach infections. Methods In this prospective, observational study, the Symptom Checklist-90 questionnaire was completed by military recruits before and following a 3-month basic training programme. H. pylori immunoglobulin (Ig)G levels, C14-urea breath-test values and levels of cortisol, catecholamine, and certain humoral and cellular immune responses were measured before and after the basic training. Results For 60 military recruits, somatization, depression and paranoid ideation scores were significantly increased after, compared with before, basic training. Post-training H. pylori IgG detection revealed three additional cases of H. pylori infection. Post-training C14-urea breath-test values were significantly higher compared with before training – thus suggesting higher levels of H. pylori colonization in the stomach. Post-training cortisol and catecholamine levels were increased, while serum IgG levels were decreased; complement component (C)3 and C4 levels remained unchanged. Post-training CD4+ and CD8+ T-cell percentages and the CD4+/CD8+ ratio were significantly reduced compared with before training. Serum interleukin (IL)-2 levels were lower and IL-10 levels were higher following training and there was a significant decrease in the IL-2/IL-10 ratio. Conclusion Military stress may reduce humoral and cellular immune responses and may aggravate the severity of H. pylori infection. PMID:26800706

Annexin II-binding immunoglobulins in patients with lupus nephritis and their correlation with disease manifestations.

PubMed

Cheung, Kwok Fan; Yung, Susan; Chau, Mel K M; Yap, Desmond Y H; Chan, Kwok Wah; Lee, Cheuk Kwong; Tang, Colin S O; Chan, Tak Mao

2017-04-25

Annexin II on mesangial cell surface mediates the binding of anti-dsDNA antibodies and consequent downstream inflammatory and fibrotic processes. We investigated the clinical relevance of circulating annexin II-binding immunoglobulins (Igs) in patients with severe proliferative lupus nephritis, and renal annexin II expression in relation to progression of nephritis in New Zealand Black and White F1 mice (NZBWF1/J) mice. Annexin II-binding Igs in serum were measured by ELISA. Ultrastructural localization of annexin II was determined by electron microscopy. Seropositivity rates for annexin II-binding IgG and IgM in patients with active lupus nephritis were significantly higher compared with controls (8.9%, 1.3% and 0.9% for annexin II-binding IgG and 11.1%, 4.0% and 1.9% for annexin II-binding IgM for patients with active lupus nephritis, patients with non-lupus renal disease and healthy subjects respectively). In lupus patients, annexin II-binding IgM level was higher at disease flare compared with remission. Annexin II-binding IgG and IgM levels were associated with that of anti-dsDNA and disease activity. Annexin II-binding IgG and IgM levels correlated with histological activity index in lupus nephritis biopsy samples. In NZBWF1/J mice, serum annexin II-binding IgG and IgM levels and glomerular annexin II and p11 expression increased with progression of active nephritis. Annexin II expression was present on mesangial cell surface and in the mesangial matrix, and co-localized with electron-dense deposits along the glomerular basement membrane. Our results show that circulating annexin II-binding IgG and IgM levels are associated with clinical and histological disease activity in proliferative lupus nephritis. The co-localization of annexin II and p11 expression with immune deposition in the kidney suggests pathogenic relevance. © 2017 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

Alteration of circulating natural autoantibodies to CD25-derived peptide antigens and FOXP3 in non-small cell lung cancer.

PubMed

Zhao, Huan; Zhang, Xuan; Han, Zhifeng; Xie, Wenjing; Yang, Wei; Wei, Jun

2018-06-29

Natural autoantibody is a key component for immune surveillance function. Regulatory T (Treg) cells play indispensable roles in promoting tumorigenesis via immune escape mechanisms. Both CD25 and FOXP3 are specific markers for Treg cells and their natural autoantibodies may be involved in anticancer activities. This work was designed to develop an in-house enzyme-linked immunosorbent assay (ELISA) to examine plasma natural IgG against CD25 and FOXP3 in non-small cell lung cancer (NSCLC). Compared with control subjects, NSCLC patients had significantly higher levels of plasma IgG for CD25a (Z = -8.05, P < 0.001) and FOXP3 (Z = -4.17, P < 0.001), lower levels for CD25b (Z = -3.58, P < 0.001), and a trend toward lower levels for CD25c (Z = -1.70, P = 0.09). Interestingly, the anti-CD25b IgG assay had a sensitivity of 25.0% against a specificity of 95.0% in an early stage patients (T 1 N 0 M 0 ) who showed the lowest anti-CD25b IgG levels among 4 subgroups classified based on staging information. Kaplan-Meier survival analysis showed that patients with high anti-FOXP3 IgG levels had shorter survival than those with low anti-FOXP3 IgG levels (χ 2  = 3.75, P = 0.05). In conclusion, anti-CD25b IgG may be a promising biomarker in terms of screening individuals at high risk of lung cancer.

Prevalence of IgG-mediated food intolerance among patients with allergic symptoms.

PubMed

Shakoor, Zahid; AlFaifi, Abrar; AlAmro, Bayan; AlTawil, Lama Nabil; AlOhaly, Rana Yazid

2016-01-01

Food intolerance mediated by food specific IgG antibodies has been implicated in a variety of disorders. To assess the prevalence of food specific IgG antibodies among patients clinically presenting with allergic symptoms lacking laboratory evidence of allergy. Descriptive retrospective cross-sectional study. King Khalid University Hospital, Riyadh between 2010-2015. Patients were screened for food specific IgG antibodies. All symptomatic patients lacking laboratory evidence of allergy who underwent food specific IgG testing during the study duration were included. Levels of IgG antibodies in patients with unidentified allergic symptoms. We selected 71 patients with allergic symptoms lacking laboratory evidence of allergy. There were 49 female and 22 male patients mean age 38.8 (16.0) years. The majority (85.7%) had urticaria. The most frequently occurring food specific IgG antibodies were against cola nut in 80.3% of patients followed by yeast in 78.9%, wheat in 77.5%, red kidney bean in 71.8%, pea in 63.4%, corn in 62% and egg white in 62% of the patients. Compared with male patients, females harbored significantly higher food specific IgG antibodies for frequently occurring food materials, particularly against wheat (74% vs 25.5%; P < .0001), corn (77.3% vs 22.7%; P < .0001) and cola nut (71.9% vs 28.1%; P < .001). Patients aged less than 40 years had higher levels of food specific IgG against gliadin (P < .003), egg white (P < .03) and barley (P < .05) compared with older patients. The detection of a variety of food specific IgG antibodies among patients with allergic symptoms indicates a possible link to food intolerance allergy. Females are prone to develop food intolerance more than males. Difficulty of comparison of results with previous studies because of lack of data. Follow-up studies could not be performed to assess the effects of elimination from the diet due to limited time allocated for this study.

Age related IgG subclass concentrations in asthma.

PubMed

Hoeger, P H; Niggemann, B; Haeuser, G

1994-03-01

The prevalence of IgG subclass deficiency in asthma is still controversial. Earlier studies often included patients receiving treatment with systemic steroids which can induce hypogammaglobulinaemia. Concentrations of IgG subclasses were studies in 200 children (aged 2-17 years) with asthma (mean asthma severity score (ASS) 2, range 1-4) who had not received systemic steroids for at least six weeks before investigation, and in 226 healthy age matched controls. The mean concentrations of IgG subclasses in children with asthma were within the 1SD range of those of the control group. In the group with asthma there was a trend towards higher levels of IgG1 and IgG4, whereas the number of children with low concentrations of IgG2 (< 2 SD of control serum samples; absolute concentrations 0.08-1.25 g/l) was slightly greater than in the group who did not have asthma (4.5 v 2.2%). Patients with subnormal concentrations of IgG2 could not be distinguished clinically or on the basis of case history and additional immunological studies did not show further abnormalities. Patients with severe asthma (ASS 3-4) had significantly higher concentrations of IgG4 (mean (SE) 0.53 (0.09) v 0.26 (0.04) g/l) than patients with mild asthma (ASS 1). No significant difference in subclass concentration was found between patients with atopic and those with non-atopic asthma. It is concluded that in an unselected group of children with asthma the mean IgG subclass concentrations do not differ significantly from a group of healthy age matched controls.

Hypogammaglobulinaemia in nephrotic rats is attributable to hypercatabolism of IgG.

PubMed Central

Beaman, M; Oldfield, S; MacLennan, I C; Michael, J; Adu, D

1988-01-01

The effect of the nephrotic syndrome induced by puromycin aminonucleoside (PA) in rats on specific antibody responses to 2,4 dinitrophenyl (DNP) conjugated to either spider crab haemocyanin (MSH), a T cell-dependent antigen, or hydroxyethyl starch (HES), a T cell-independent type 2 antigen were studied. The serum IgG anti-DNP levels following immunization with both antigens were reduced in nephrotic animals compared with controls while IgM anti-DNP antibody titres were higher. The half-life of IgG anti-DNP antibodies passively transferred into non-immunized nephrotic rats was markedly reduced while the half-life of anti-DNP antibodies of the IgM class was comparable to that in controls. Low serum IgG and elevated IgM levels were seen in nephrotic animals compared to controls. Antibody-forming cells specific for DNP were demonstrated by immunohistology on rat spleens and the numbers of both IgG and IgM-producing cells were found to be significantly increased (P less than 0.05) in nephrotic animals in response to both DNP-HES and DNP-MSH. These data indicate that in nephrotic rats the alteration seen in the serum immunoglobulin levels is not attributable to reduced antibody production but increased catabolism of serum IgG antibodies. PMID:3233791

Variable Food-Specific IgG Antibody Levels in Healthy and Symptomatic Chinese Adults

PubMed Central

Wu, Liu-Xin; Li, Hong; Sun, Zhi-Jian; Li, Jing-Bo; Jiang, Hong-Xia; Chen, Zhi-Heng; Wang, Qi-Bin; Chen, Wei-Wei

2013-01-01

Background The presence of food-specific IgG antibodies in human serum may be useful for diagnosis of adverse food reactions. However, the clinical utility of tesing for such antibodies remains very controversial. The aim of this study was to evaluate the serum levels and population distribution of food-specific IgGs and their association with chronic symptoms in a large-scale Chinese population. Methodology/Principal Findings A total of 21305 adult participants from different regions of China had 14 type of food-specific serum IgG antibodies that were measured by enzyme-linked immunosorbent assay. Amongthese, 5,394 participants were randomly chosen to complete follow-up questionnaire surveys on their dietary characteristics and chronic symptoms. The concentrations of food-specific IgGs against 14 foods ranged from a median (interquartile range) of 7.3 (3.8, 12.6) U/mL of pork-specfic IgG to 42.3 (28.8, 60.2) U/mL of crab-specific IgG. The concentration of food-specific IgGs was closely related to gender; after adjustment for region and age, women had higher concentrations of food-specific IgGs against all of the 14 foods except chicken (regression coefficient (95% CI): 0.01 (−0.003, 0.023); P = 0.129) and corn (0.002 (−0.013, 0.016); P = 0.825). Similar results were also found in the relationship of geographic region to the food-specific IgG concentrations for the 14 foods. Chronic symptoms were negatively associated with the concentrations of a few food-specific IgGs, and were positively associated with the concentrations of other food-specific IgGs. Conclusions The levels of food-specific IgGs were variable both in healthy and in symptomatic Chinese adults. These findings raise awareness that demographic factors, the type of food and specific chronic symptoms should be considered before food elimination treatment based on IgG testing in patients with chronic symptoms is used in clinical practice. PMID:23301096

IgG abnormality in narcolepsy and idiopathic hypersomnia.

PubMed

Tanaka, Susumu; Honda, Makoto

2010-03-05

A close association between narcolepsy and the Human Leukocyte Antigen (HLA)-DQB1*0602 allele suggests the involvement of the immune system, or possibly an autoimmune process. We investigated serum IgG levels in narcolepsy. We measured the serum total IgG levels in 159 Japanese narcolepsy-cataplexy patients positive for the HLA-DQB1*0602 allele, 28 idiopathic hypersomnia patients with long sleep time, and 123 healthy controls (the HLA-DQB1*0602 allele present in 45 subjects). The serum levels of each IgG subclass were subsequently measured. The distribution of serum IgG was significantly different among healthy controls negative for the HLA-DQB1*0602 allele (11.66+/-3.55 mg/ml), healthy controls positive for the HLA-DQB1*0602 allele (11.45+/-3.43), narcolepsy patients (9.67+/-3.38), and idiopathic hypersomnia patients (13.81+/-3.80). None of the following clinical variables, age, disease duration, Epworth Sleepiness Scale, smoking habit and BMI at the time of blood sampling, were associated with IgG levels in narcolepsy or idiopathic hypersomnia. Furthermore we found the decrease in IgG1 and IgG2 levels, stable expression of IgG3, and the increase in the proportion of IgG4 in narcolepsy patients with abnormally low IgG levels. The increase in the proportion of IgG4 levels was also found in narcolepsy patients with normal serum total IgG levels. Idiopathic hypersomnia patients showed a different pattern of IgG subclass distribution with high IgG3 and IgG4 level, low IgG2 level, and IgG1/IgG2 imbalance. Our study is the first to determine IgG abnormalities in narcolepsy and idiopathic hypersomnia by measuring the serum IgG levels in a large number of hypersomnia patients. The observed IgG abnormalities indicate humoral immune alterations in narcolepsy and idiopathic hypersomnia. Different IgG profiles suggest immunological differences between narcolepsy and idiopathic hypersomnia.

Inverse Association of Plasma IgG Antibody to Aggregatibacter actinomycetemcomitans and High C-Reactive Protein Levels in Patients with Metabolic Syndrome and Periodontitis.

PubMed

Thanakun, Supanee; Pornprasertsuk-Damrongsri, Suchaya; Gokyu, Misa; Kobayashi, Hiroaki; Izumi, Yuichi

2016-01-01

The association between clinically diagnosed periodontitis, a common chronic oral infection, and metabolic syndrome has been previously reported. The aim of this study was to investigate the association of plasma IgG levels against Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Prevotella intermedia, C-reactive protein, and periodontal status with metabolic syndrome. Plasma IgG levels and C-reactive protein were measured by enzyme-linked immunosorbent assay, and salivary levels of A. actinomycetemcomitans and P. gingivalis were determined by quantitative real-time polymerase chain reaction. Among 127 individuals aged 35-76 years, 57 participants had metabolic syndrome and severe periodontitis, 25 had metabolic syndrome and an absence of severe periodontitis, 17 healthy individuals had severe periodontitis, and 28 healthy individuals were without severe periodontitis. Patients with metabolic syndrome had reduced humoral immune response to A. actinomycetemcomitans (p = 0.008), regardless of their salivary levels or periodontitis status compared with healthy participants. The IgG antibody response to P. gingivalis, regardless of their salivary levels or participants' health condition, was significantly higher in severe periodontitis patients (p<0.001). Plasma IgG titers for P. intermedia were inconsistent among metabolic syndrome or periodontal participants. Our results indicate that the presence of lower levels of IgG antibodies to A. actinomycetemcomitans (OR = 0.1; 95%CI 0.0-0.7), but not P. gingivalis, a severe periodontitis status (OR = 7.8; 95%CI 1.1-57.0), high C-reactive protein levels (OR = 9.4; 95%CI 1.0-88.2) and body mass index (OR = 3.0; 95%CI 1.7-5.2), are associated with the presence of metabolic syndrome. The role of the decreased IgG antibody response to A. actinomycetemcomitans, increased C-reactive protein levels on the association between periodontal disease and metabolic syndrome in a group of Thai patients is suggested.

Associations of social environment, socioeconomic position and social mobility with immune response in young adults: the Jerusalem Perinatal Family Follow-Up Study

PubMed Central

Lawrence, Gabriella M; Friedlander, Yehiel; Calderon-Margalit, Ronit; Enquobahrie, Daniel A; Huang, Jonathan Yinhao; Tracy, Russell P; Manor, Orly; Siscovick, David S; Hochner, Hagit

2017-01-01

Objectives Immune response to cytomegalovirus (CMV) impacts adult chronic disease. This study investigates associations of childhood and adulthood social environment, socioeconomic position (SEP) and social mobility with CMV response in young adults. Design Historical prospective study design. Setting Subcohort of all 17 003 births to residents of Jerusalem between 1974 and 1976. Participants Participants included 1319 young adults born in Jerusalem with extensive archival and follow-up data, including childhood and adulthood SEP-related factors and anti-CMV IgG titre levels and seroprevalence measured at age 32. Main exposure and outcome measures Principal component analysis was used to transform correlated social environment and SEP-related variables at two time points (childhood and adulthood) into two major scores reflecting household (eg, number of siblings/children, religiosity) and socioeconomic (eg, occupation, education) components. Based on these components, social mobility variables were created. Linear and Poisson regression models were used to investigate associations of components and mobility with anti-CMV IgG titre level and seroprevalence, adjusted for confounders. Results Lower levels of household and socioeconomic components in either childhood or adulthood were associated with higher anti-CMV IgG titre level and seropositivity at age 32. Compared with individuals with stable favourable components, anti-CMV IgG titre level and risk for seropositivity were higher in stable unfavourable household and socioeconomic components (household: β=3.23, P<0.001; relative risk (RR)=1.21, P<0.001; socioeconomic: β=2.20, P=0.001; RR=1.14, P=0.01), downward household mobility (β=4.32, P<0.001; RR=1.26, P<0.001) and upward socioeconomic mobility (β=1.37, P=0.04; RR=1.19, P<0.001). Among seropositive individuals, associations between household components and mobility with anti-CMV IgG titre level were maintained and associations between socioeconomic components and mobility with anti-CMV IgG titre level were attenuated. Conclusions Our study provides evidence that accumulating low SEP from childhood through adulthood and social mobility may compromise immune response in young adulthood. PMID:29273651

Detection of serum antibodies against measles, mumps and rubella after primary measles, mumps and rubella (MMR) vaccination in children.

PubMed

Rafiei Tabatabaei, Sedigheh; Esteghamati, Abdoul-Reza; Shiva, Farideh; Fallah, Fatemeh; Radmanesh, Raheleh; Abdinia, Babak; Shamshiri, Ahmad Reza; Khairkhah, Masoumeh; Shekari Ebrahimabad, Hamideh; Karimi, Abdollah

2013-01-01

In Iran, the measles, mumps and rubella vaccine (MMR) is administered in a two-dose protocol where the first dose is scheduled at 12 months of age. This study aims to determine the efficacy of the MMR vaccine by testing IgM and IgG antibody levels 4 - 7 weeks after primary vaccination. A single group cohort study was performed on healthy children, 12 - 15 months of age, who were vaccinated at health centers affiliated with Shahid Beheshti University of Medical Sciences in Tehran, from January to April 2009. Children with negative vaccination and/or clinical history for measles, mumps or rubella were administered the first dose of the MMR live attenuated vaccine. IgG and IgM antibodies were checked by enzyme linked immunoassay (ELISA) in serum samples 4 - 7 weeks after vaccination. A child was considered seropositive if antibody levels were higher than the assay cut-off level set by the ELISA kit. Samples from 240 children were checked for antibodies against measles and rubella. Measles serum IgM level was positive in 71.7% of samples and IgG in 75.8%. The rubella serum IgM level was positive in 71.7% of children and IgG in 73.8%. From 190 blood samples that were checked for mumps antibodies, serum IgM was positive in 68.9% and IgG in 95.3%. No significant relationship was found between seropositivity and age or gender. IgG and IgM antibody levels were below the assay cut-off levels against measles and rubella in approximately one-fourth of the children following primary MMR vaccination. A second dose was necessary to raise the level of protection against measles and rubella.

[IgG4-related disease: patient group characterization and rituximab therapy].

PubMed

Sedyshev, S Kh; Vasil'ev, V I; Kovrigina, A M; Logvinenko, O A; Rodionova, E B; Safonova, T N; Gaĭduk, I V; Silin, A Iu; Komov, D V; Nasonov, E L

2013-01-01

To characterize a group of patients with IgG4-related disease (IgG4-RD) in a Russian population and to evaluate the efficiency of rituximab therapy. In 2009 to 2011, at the Research Institute of Rheumatology, Russian Academy of Medical Sciences, 30 patients (16 men and 14 women; mean age 44 years) were diagnosed with IgG4-RD that was confirmed by determination of serum IgG4 levels and immunohistochemical study of biopsy samples stained for IgG4-positive plasma cells. Seven patients received rituximab therapy. It was assumed at baseline that there were different types of neoplasias in 12 (40%), non-Hodgkin's and Hodgkin's lymphomas in 10 (33.3%), Sjögren's syndrome in 5 (16.7%), and Wegener's granulomatosis in 3 (10%). When 2 or more locations were involved, the condition was regarded as multifocal fibrosclerosis (33.3%). Localized forms were revealed in 20 (66.7%) patients. Among them, the largest number of patients was those who had orbital pseudotumor, Mikulicz's disease, or retroperitoneal fibrosclerosis. The most common sites of involvement were orbits (66.7%), salivary glands (70%) and lymph nodes (36.7%). Comparison of serum IgG4 levels in 28 patients with IgG4-RD, 22 patients with Sjögren's disease, salivary and lacrimal gland lymphomas, and 10 healthy controls showed that the concentration of IgG4 was significantly higher in Group 1 (median 2.6 g/I; IQR 1.22-4.65 (p < 0.001). Tissue IgG4/IgG ratio varied from 25 to 50% and averaged 38%. A moiré-like pattern of varying fibrosis was noted in 83% of cases. Analysis of laboratory data revealed elevated C-reactive protein concentrations (46.7% with a mean of 39.5 mg/l; normal values < 5.0 mg/l), increased erythrocyte sedimentation rate (60% with a mean of 37.6 mm/h), hypergammaglobulinemia (30% with a mean of 29.4%; normal range 13-22%), and rheumatoid factor (23.3%). After rituximab therapy, all the patients showed a decrease of IgG4 levels to the normal levels and positive changes evidenced by visualization techniques (computed tomography, magnetic resonance imaging). IgG4-RD is a novel problem in modern medicine, which requires a multidisciplinary approach and further study. Rituximab therapy is a promising treatment.

Assessment of Industrial Antimony Exposure and Immunologic Function for Workers in Taiwan.

PubMed

Wu, Chin-Ching; Chen, Yi-Chun

2017-06-26

This study investigated antimony exposure among employees in industries in Taiwan and evaluated whether their immunologic markers were associated with antimony exposure. We recruited 91 male workers and 42 male office administrators from 2 glass manufacturing plants, 1 antimony trioxide manufacturing plants, and 2 engineering plastic manufacturing plants. Air samples were collected at worksites and administrative offices, and each participant provided specimens of urine, blood, and hair to assay antimony levels. We also determined white blood cells, lymphocyte, and monocyte, IgA, IgE, and IgG in blood specimens. The mean antimony concentration in the air measured at worksites was much higher in the antimony trioxide plant (2.51 ± 0.57 mg/m³) than in plastic plants (0.21 ± 0.06 mg/m³) and glass plants (0.14 ± 0.01 mg/m³). Antimony levels in blood, urine, and hair measured for participants were correlated with worksites and were higher in workers than in administrators. The mean serum IgG, IgA, and IgE levels were lower in workers than in administrators ( p < 0.001). Serum IgA and IgE levels in participants were negatively associated with antimony levels in air samples of workplaces, and in blood, urine, and hairs of participants. Serum IgG and IgE of all participants were also negatively associated with antimony levels in their hairs. In conclusion, the antimony exposure is greater for workers employed in the five industrial plants than for administrators. This study suggests serum IgG, IgA, and IgE levels are negatively associated with antimony exposure.

Assessment of Industrial Antimony Exposure and Immunologic Function for Workers in Taiwan

PubMed Central

Wu, Chin-Ching; Chen, Yi-Chun

2017-01-01

This study investigated antimony exposure among employees in industries in Taiwan and evaluated whether their immunologic markers were associated with antimony exposure. We recruited 91 male workers and 42 male office administrators from 2 glass manufacturing plants, 1 antimony trioxide manufacturing plants, and 2 engineering plastic manufacturing plants. Air samples were collected at worksites and administrative offices, and each participant provided specimens of urine, blood, and hair to assay antimony levels. We also determined white blood cells, lymphocyte, and monocyte, IgA, IgE, and IgG in blood specimens. The mean antimony concentration in the air measured at worksites was much higher in the antimony trioxide plant (2.51 ± 0.57 mg/m3) than in plastic plants (0.21 ± 0.06 mg/m3) and glass plants (0.14 ± 0.01 mg/m3). Antimony levels in blood, urine, and hair measured for participants were correlated with worksites and were higher in workers than in administrators. The mean serum IgG, IgA, and IgE levels were lower in workers than in administrators (p < 0.001). Serum IgA and IgE levels in participants were negatively associated with antimony levels in air samples of workplaces, and in blood, urine, and hairs of participants. Serum IgG and IgE of all participants were also negatively associated with antimony levels in their hairs. In conclusion, the antimony exposure is greater for workers employed in the five industrial plants than for administrators. This study suggests serum IgG, IgA, and IgE levels are negatively associated with antimony exposure. PMID:28672853

Altered glycosylation of complexed native IgG molecules is associated with disease activity of systemic lupus erythematosus.

PubMed

Sjöwall, C; Zapf, J; von Löhneysen, S; Magorivska, I; Biermann, M; Janko, C; Winkler, S; Bilyy, R; Schett, G; Herrmann, M; Muñoz, L E

2015-05-01

In addition to the redundancy of the receptors for the Fc portion of immunoglobulins, glycans result in potential ligands for a plethora of lectin receptors found in immune effector cells. Here we analysed the exposure of glycans containing fucosyl residues and the fucosylated tri-mannose N-type core by complexed native IgG in longitudinal serum samples of well-characterized patients with systemic lupus erythematosus. Consecutive serum samples of a cohort of 15 patients with systemic lupus erythematosus during periods of increased disease activity and remission were analysed. All patients fulfilled the 1982 American College of Rheumatology classification criteria. Sera of 15 sex- and age-matched normal healthy blood donors served as controls. The levels and type of glycosylation of complexed random IgG was measured with lectin enzyme-immunosorbent assays. After specifically gathering IgG complexes from sera, biotinylated lectins Aleuria aurantia lectin and Lens culinaris agglutinin were employed to detect IgG-associated fucosyl residues and the fucosylated tri-mannose N-glycan core, respectively. In sandwich-ELISAs, IgG-associated IgM, IgA, C1q, C3c and C-reactive protein (CRP) were detected as candidates for IgG immune complex constituents. We studied associations of the glycan of complexed IgG and disease activity according to the physician's global assessment of disease activity and the systemic lupus erythematosus disease activity index 2000 documented at the moment of blood taking. Our results showed significantly higher levels of Aleuria aurantia lectin and Lens culinaris agglutinin binding sites exposed on IgG complexes of patients with systemic lupus erythematosus than on those of normal healthy blood donors. Disease activity in systemic lupus erythematosus correlated with higher exposure of Aleuria aurantia lectin-reactive fucosyl residues by immobilized IgG complexes. Top levels of Aleuria aurantia lectin-reactivity were found in samples taken during the highest activity of systemic lupus erythematosus. Our results show that native circulating IgG complexes from active systemic lupus erythematosus patients expose fucosyl residues and their glycan core is accessible to soluble lectins. Two putative mechanisms may contribute to the increased exposure of these glycans: (1) the canonical N-glycosylation site of the IgG-CH2 domain; (2) an IgG binding non-IgG molecule, like complement or C-reactive protein. In both cases the complexed IgG may be alternatively targeted to lectin receptors of effector cells, e.g. dendritic cells. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Prenatal and Newborn Immunoglobulin Levels from Mother-Child Pairs and Risk of Autism Spectrum Disorders

PubMed Central

Grether, Judith K.; Ashwood, Paul; Van de Water, Judy; Yolken, Robert H.; Anderson, Meredith C.; Torres, Anthony R.; Westover, Jonna B.; Sweeten, Thayne; Hansen, Robin L.; Kharrazi, Martin; Croen, Lisa A.

2016-01-01

Background: An etiological role for immune factors operating during early brain development in children with autism spectrum disorders (ASD) has not yet been established. A major obstacle has been the lack of early biologic specimens that can be linked to later diagnosis. In a prior study, we found lower risk of ASD associated with higher levels of maternally-derived total IgG and Toxoplasmosis gondii (Toxo) IgG in newborn blood spot specimens from children later diagnosed with ASD compared to population controls. Methods: We obtained maternal mid-gestational serum specimens and newborn screening blood spots from the California Genetics Disease Screening Program (GDSP) for linked mother-baby pairs for 84 children with ASD and 49 children with developmental delay but not ASD (DD) identified from California Department of Developmental Services records and for 159 population controls sampled from birth certificates.Immunoglobulin levels in maternal and newborn specimens were measured by solid phase immunoassays and analyzed in logistic regression models for total IgG, total IgM, and Toxo IgG, and, for maternal specimens only, Toxo IgM. Correlations between maternal and newborn ranked values were evaluated. Results: In both maternal and newborn specimens, we found significantly lower risk of ASD associated with higher levels of Toxo IgG. In addition, point estimates for all comparisons were < 1.0 suggesting an overall pattern of lower immunoglobulin levels associated with higher ASD risk but most did not reach statistical significance. We did not find differences in maternal or newborn specimens comparing children with DD to controls. Discussion: These results are consistent with evidence from our prior study and other published reports indicating that immune factors during early neurodevelopment may be etiologically relevant to ASD. Lowered immunoglobulin levels may represent suboptimal function of the maternal immune system or reduced maternal exposure to common infectious agents. Conclusion: Patterns seen in these selected immunoglobulins may provide clues to mechanisms of early abnormalities in neurodevelopment contributing to ASD. We recommend further study of immunoglobulin profiles in larger samples of linked mother-baby pairs to evaluate possible etiologic relevance. PMID:27242422

Prenatal and Newborn Immunoglobulin Levels from Mother-Child Pairs and Risk of Autism Spectrum Disorders.

PubMed

Grether, Judith K; Ashwood, Paul; Van de Water, Judy; Yolken, Robert H; Anderson, Meredith C; Torres, Anthony R; Westover, Jonna B; Sweeten, Thayne; Hansen, Robin L; Kharrazi, Martin; Croen, Lisa A

2016-01-01

An etiological role for immune factors operating during early brain development in children with autism spectrum disorders (ASD) has not yet been established. A major obstacle has been the lack of early biologic specimens that can be linked to later diagnosis. In a prior study, we found lower risk of ASD associated with higher levels of maternally-derived total IgG and Toxoplasmosis gondii (Toxo) IgG in newborn blood spot specimens from children later diagnosed with ASD compared to population controls. We obtained maternal mid-gestational serum specimens and newborn screening blood spots from the California Genetics Disease Screening Program (GDSP) for linked mother-baby pairs for 84 children with ASD and 49 children with developmental delay but not ASD (DD) identified from California Department of Developmental Services records and for 159 population controls sampled from birth certificates.Immunoglobulin levels in maternal and newborn specimens were measured by solid phase immunoassays and analyzed in logistic regression models for total IgG, total IgM, and Toxo IgG, and, for maternal specimens only, Toxo IgM. Correlations between maternal and newborn ranked values were evaluated. In both maternal and newborn specimens, we found significantly lower risk of ASD associated with higher levels of Toxo IgG. In addition, point estimates for all comparisons were < 1.0 suggesting an overall pattern of lower immunoglobulin levels associated with higher ASD risk but most did not reach statistical significance. We did not find differences in maternal or newborn specimens comparing children with DD to controls. These results are consistent with evidence from our prior study and other published reports indicating that immune factors during early neurodevelopment may be etiologically relevant to ASD. Lowered immunoglobulin levels may represent suboptimal function of the maternal immune system or reduced maternal exposure to common infectious agents. Patterns seen in these selected immunoglobulins may provide clues to mechanisms of early abnormalities in neurodevelopment contributing to ASD. We recommend further study of immunoglobulin profiles in larger samples of linked mother-baby pairs to evaluate possible etiologic relevance.

Characterization of the basic charge variants of a human IgG1

PubMed Central

Lu, Franklin; Derfus, Gayle; Kluck, Brian; Nogal, Bartek; Emery, Craig; Summers, Christie; Zheng, Kai; Bayer, Robert; Amanullah, Ashraf

2011-01-01

We report a case study of an IgG1 with a unique basic charge variant profile caused by C-terminal proline amidation on either one or two heavy chains. The proline amidation was sensitive to copper ion concentration in the production media during cell culture: the higher the Cu2+ ion concentration, the higher the level of proline amidation detected. This conclusion was supported by the analysis of samples that revealed direct correlation between the proline amidation level observed from peptide maps and the level of basic peaks measured by imaged capillary isoelectric focusing and a pH gradient ion-exchange chromatography method. The importance of these observations to therapeutic antibody production is discussed. PMID:22123059

Characterization of the basic charge variants of a human IgG1: effect of copper concentration in cell culture media.

PubMed

Kaschak, Timothy; Boyd, Daniel; Lu, Franklin; Derfus, Gayle; Kluck, Brian; Nogal, Bartek; Emery, Craig; Summers, Christie; Zheng, Kai; Bayer, Robert; Amanullah, Ashraf; Yan, Boxu

2011-01-01

We report a case study of an IgG1 with a unique basic charge variant profile caused by C-terminal proline amidation on either one or two heavy chains. The proline amidation was sensitive to copper ion concentration in the production media during cell culture: the higher the Cu ( 2+) ion concentration, the higher the level of proline amidation detected. This conclusion was supported by the analysis of samples that revealed direct correlation between the proline amidation level observed from peptide maps and the level of basic peaks measured by imaged capillary isoelectric focusing and a pH gradient ion-exchange chromatography method. The importance of these observations to therapeutic antibody production is discussed.

IgG Avidity Test in Congenital Toxoplasmosis Diagnoses in Newborns

PubMed Central

Cardoso Fonseca, Zulmirene; Xavier Rodrigues, Isolina Maria; Cruz e Melo, Natália; Boaventura Avelar, Juliana; Castro, Ana Maria; Martins Avelino, Mariza

2017-01-01

The goal of this study was to investigate the importance of IgG avidity testing in newborns (NBs) diagnosed with early congenital toxoplasmosis. We collected samples from 88 puerperae infected by Toxoplasma gondii (T. gondii) and their NBs (48 acutely-infected puerperae (AIP) and 40 chronically-infected puerperae (CIP)), from two public maternity hospitals in Goiania city, Goias, Brazil, from 2010 to 2015. Specific anti-T. gondii IgM and IgG serum levels and IgG avidity tests were evaluated using chemiluminescence. Congenital toxoplasmosis was observed in 66.66% (n = 32) of NBs with AIP, 94.1% presenting low avidity (LA) and 51.61% presenting high avidity (HA) test results. The IgG and IgM levels of NBs with LA and their puerperae were higher in comparison with HA NBs and puerperae (p = 0.0001). The avidity tests showed 100% specificity and 50% sensitivity (p = 0.0001). NBs with LA had a 15-fold increased risk of developing congenital toxoplasmosis in comparison with HA NBs. The IgG avidity test could be used to assist in early congenital toxoplasmosis diagnoses in NBs and LA, identifying a greater probability of vertical transmission. PMID:28629167

Detection of glycosylation abnormality in rheumatoid IgG using N-acetylglucosamine-specific Psathyrella velutina lectin.

PubMed

Tsuchiya, N; Endo, T; Matsuta, K; Yoshinoya, S; Takeuchi, F; Nagano, Y; Shiota, M; Furukawa, K; Kochibe, N; Ito, K

1993-07-15

Although the galactose deficiency in the Asn297-linked sugar chains of serum IgG from patients with rheumatoid arthritis (RA) has been established, structural analysis of sugar chains has not been readily available. Psathyrella velutina lectin (PVL) preferentially interacts with the N-acetylglucosamine beta 1-->2Man group, exposed at the termini of sugar chains in agalacto IgG. Biotinylated PVL reacted strongly in Western blotting with H chains of IgG derived from patients with RA. An ELISA-based assay for the detection of agalacto IgG was developed using recombinant protein G and biotinylated PVL in combination, and the screening of patients' sera was performed. PVL binding of serum IgG significantly correlated with percentage of galactose-deficient IgG determined by the structural analysis. Age-related slight increase in PVL binding was observed among normal controls. Patients with RA showed significantly higher PVL binding (37.90 +/- 42.25 U/ml, n = 93) as compared with normal controls (5.75 +/- 2.92 U/ml, n = 112) (p = 0.0001). Patients with SLE showed lower but still significant PVL binding (17.86 +/- 5.18 U/ml, n = 10, p = 0.0001). PVL binding correlated with C-reactive protein level in serial analysis of individual RA patients, and was significantly higher in the synovial fluid compared with paired serum samples. PVL binding assay may provide an ideal tool for the simple and sensitive detection of agalacto IgG.

Hypogammaglobulinemia in newly diagnosed chronic lymphocytic leukemia: Natural history, clinical correlates, and outcomes.

PubMed

Parikh, Sameer A; Leis, Jose F; Chaffee, Kari G; Call, Timothy G; Hanson, Curtis A; Ding, Wei; Chanan-Khan, Asher A; Bowen, Deborah; Conte, Michael; Schwager, Susan; Slager, Susan L; Van Dyke, Daniel L; Jelinek, Diane F; Kay, Neil E; Shanafelt, Tait D

2015-09-01

Although hypogammaglobulinemia is a well recognized complication in patients with chronic lymphocytic leukemia (CLL), its prevalence at the time of CLL diagnosis, and association with novel prognostic markers and clinical outcome is not well understood. All patients at the Mayo Clinic between January 1999 and July 2013 who had newly diagnosed CLL and had a baseline assessment of serum immunoglobulin G (IgG) were included. The relation between hypogammaglobulinemia at diagnosis and the novel prognostic parameters time to first treatment (TFT) and overall survival (OS) were evaluated. Of 1485 patients who met the eligibility criteria, 382 (26%) had hypogammaglobulinemia (median IgG, 624 mg/dL), whereas the remaining 1103 patients (74%) had normal serum IgG levels (median IgG, 1040 mg/dL). Patients who had hypogammaglobulinemia at diagnosis were more likely to have advanced Rai stage (III-IV; P = .001) and higher expression of CD49d (P < .001) compared with patients who had normal IgG levels. Although the median TFT for patients who had hypogammaglobulinemia was shorter compared with that for patients who had normal IgG levels (3.8 years vs 7.4 years; P < .001), on multivariable analysis, there was no difference in OS between these 2 groups (12.8 years vs 11.3 years, respectively; P = .73). Of 1103 patients who had CLL with normal IgG levels at diagnosis and who did not receive CLL therapy, the risk of acquired hypogammaglobulinemia was 11% at 5 years and 23% at 10 years. Hypogammaglobulinemia is present in 25% of patients with newly diagnosed CLL. Approximately 25% of patients who have CLL with normal IgG levels at diagnosis will subsequently develop hypogammaglobulinemia on long-term follow-up. The presence of hypogammaglobulinemia does not appear to impact overall survival. © 2015 American Cancer Society.

Stringently Defined Otitis Prone Children Demonstrate Deficient Naturally Induced Mucosal Antibody Response to Moraxella catarrhalis Proteins

PubMed Central

Ren, Dabin; Murphy, Timothy F.; Lafontaine, Eric R.; Pichichero, Michael E.

2017-01-01

Moraxella catarrhalis (Mcat) is a prominent mucosal pathogen causing acute otitis media (AOM). We studied Mcat nasopharyngeal (NP) colonization, AOM frequency and mucosal antibody responses to four vaccine candidate Mcat proteins: outer membrane protein (OMP) CD, oligopeptide permease (Opp) A, hemagglutinin (Hag), and Pilin A clade 2 (PilA2) from stringently defined otitis prone (sOP) children, who experience the greatest burden of disease, compared to non-otitis prone (NOP) children. sOP children had higher NP colonization of Mcat (30 vs. 22%, P = 0.0003) and Mcat-caused AOM rates (49 vs. 24%, P < 0.0001) than NOP children. Natural acquisition of mucosal antibodies to Mcat proteins OMP CD (IgG, P < 0.0001), OppA (IgG, P = 0.018), Hag (IgG and IgA, both P < 0.0001), and PilA2 (IgA, P < 0.0001) was lower in sOP than NOP children. Higher levels of mucosal IgG to Hag (P = 0.039) and PilA2 (P = 0.0076), and IgA to OMP CD (P = 0.010), OppA (P = 0.030), and PilA2 (P = 0.043) were associated with lower carriage of Mcat in NOP but not sOP children. Higher levels of mucosal IgG to OMP CD (P = 0.0070) and Hag (P = 0.0003), and IgA to Hag (P = 0.0067) at asymptomatic colonization than those at onset of AOM were associated with significantly lower rate of Mcat NP colonization progressing to AOM in NOP compared to sOP children (3 vs. 26%, P < 0.0001). In conclusion, sOP children had a diminished mucosal antibody response to Mcat proteins, which was associated with higher frequencies of asymptomatic NP colonization and NP colonization progressing to Mcat-caused AOM. Enhancing Mcat antigen-specific mucosal immune responses to levels higher than achieved by natural exposure will be necessary to prevent AOM in sOP children. PMID:28848555

Stringently Defined Otitis Prone Children Demonstrate Deficient Naturally Induced Mucosal Antibody Response to Moraxella catarrhalis Proteins.

PubMed

Ren, Dabin; Murphy, Timothy F; Lafontaine, Eric R; Pichichero, Michael E

2017-01-01

Moraxella catarrhalis ( Mcat ) is a prominent mucosal pathogen causing acute otitis media (AOM). We studied Mcat nasopharyngeal (NP) colonization, AOM frequency and mucosal antibody responses to four vaccine candidate Mcat proteins: outer membrane protein (OMP) CD, oligopeptide permease (Opp) A, hemagglutinin (Hag), and Pilin A clade 2 (PilA2) from stringently defined otitis prone (sOP) children, who experience the greatest burden of disease, compared to non-otitis prone (NOP) children. sOP children had higher NP colonization of Mcat (30 vs. 22%, P  = 0.0003) and Mcat -caused AOM rates (49 vs. 24%, P  < 0.0001) than NOP children. Natural acquisition of mucosal antibodies to Mcat proteins OMP CD (IgG, P  < 0.0001), OppA (IgG, P  = 0.018), Hag (IgG and IgA, both P  < 0.0001), and PilA2 (IgA, P  < 0.0001) was lower in sOP than NOP children. Higher levels of mucosal IgG to Hag ( P  = 0.039) and PilA2 ( P  = 0.0076), and IgA to OMP CD ( P  = 0.010), OppA ( P  = 0.030), and PilA2 ( P  = 0.043) were associated with lower carriage of Mcat in NOP but not sOP children. Higher levels of mucosal IgG to OMP CD ( P  = 0.0070) and Hag ( P  = 0.0003), and IgA to Hag ( P  = 0.0067) at asymptomatic colonization than those at onset of AOM were associated with significantly lower rate of Mcat NP colonization progressing to AOM in NOP compared to sOP children (3 vs. 26%, P  < 0.0001). In conclusion, sOP children had a diminished mucosal antibody response to Mcat proteins, which was associated with higher frequencies of asymptomatic NP colonization and NP colonization progressing to Mcat -caused AOM. Enhancing Mcat antigen-specific mucosal immune responses to levels higher than achieved by natural exposure will be necessary to prevent AOM in sOP children.

/sup 125/I-Clq-binding and specific antibodies as indicators of pulmonary disease activity in cystic fibrosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moss, R.B.; Hsu, Y.P.; Lewiston, N.J.

1981-08-01

We studied the incidence and levels of circulating immune complexes by the /sup 125/I-Clq-binding assay in patients with cystic fibrosis in relation to clinical respiratory status and specific IgG and IgE antibodies to Pseudomonas aeruginosa. Staphylococcus aureus, Aspergillus fumigatus, and Candida albicans. Overall prevalence of CIC was 43%, but 86% of serially studied patients had evidence of CIC at some time. Patients with acute respiratory exacerbations and deteriorating pulmonary function had a higher incidence of CIC (76%) as compared to stable patients (36%, P less than 0.01), as well as significantly higher levels of CIC. Acute exacerbations were also associatedmore » with significant increases in IgG antibody to Pseudomonas (P less than 0.005) but not in other antibodies. CIC did not correlate with Pseudomonas-specific IgG nor with any other specific antibody studied. A variety of age-related differences in specific antibody levels were seen. The episodic appearance of CIC is common in CF and is usually associated with exacerbation of lung disease.« less

Serum levels of immunoglobulin free light chains in patients with chronic hepatitis C presenting cryoglobulinemia.

PubMed

Oliveira, Isabela S; Cabral, Milena S; Jesus, Larissa S; Paraná, Raymundo; Atta, Ajax M; Sousa Atta, Maria Luiza B

2014-01-01

Hepatitis C virus (HCV) infects B-lymphocytes, provokes cellular dysfunction and causes lymphoproliferative diseases such as cryoglobulinemia and non-Hodgkin's B-cell lymphoma. In the present study, we investigated the serum levels of kappa and lambda free light chains (FLC) of immunoglobulins and the kappa/lambda FLC ratio in Brazilian patients with chronic HCV infection and cryoglobulinemia. We also analyzed the immunochemical composition of the cryoglobulins in these patients. Twenty-eight cryoglobulinemic HCV patients composed the target group, while 37 HCV patients without cryoglobulinemia were included as controls. The median levels of kappa and lambda FLC were higher in patients with cryoglobulinemia compared to controls (p=0.001 and p=0.003, respectively), but the kappa/lambda FLC ratio was similar in patients with and without cryoglobulinemia (p>0.05). The median FLC ratio was higher in HCV patients presenting with advanced fibrosis of the liver compared to HCV patients without fibrosis (p=0.004). Kappa and lambda FLC levels were strongly correlated with the IgA, IgG and IgM levels in the patients with cryoglobulinemia. In patients without cryoglobulinemia, the kappa FLC level was only correlated with the IgG level, whereas the lambda FLC were weakly correlated with the IgA, IgG and IgM levels. An immunochemical pattern of mixed cryoglobulins (MC), predominantly IgM, IgG, IgA and kappa light chain, was verified in these immune complexes. We concluded that HCV-infected patients presenting cryoglobulinemia have vigorous polyclonal B-lymphocyte activation due to chronic HCV infection and persistent immune stimulation. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.

Immunological studies on bee-keepers: specific IgG and subclass typing IgG against bee venom and bee venom components.

PubMed

Urbanek, R; Forster, J; Ziupa, J; Karitzky, D

1980-11-17

Specific IgE antibodies against bee venom and its components were studied in 23 bee-keepers. The highest IgG serum levels were observed for whole bee venom followed by phospholipase A. The serum levels of specific IgG antibodies against melittin and MCD-peptide were lower, the lowest serum levels being observed for apamin. After a 5 month absence from bee-keeping a fall in the serum levels of IgG antibodies was observed in all the bee-keepers studied. The investigation of the IgG subclass antibodies 1-4 against bee venom and phospholipase A demonstrated the highest serum levels for IgG 4 and IgG 2, the lowest levels were observed for IgG 1. The lowest IgG serum levels were associated with the least effective protection to bee stings. These findings support the concept that specific IgG antibodies prevent the development of allergic symptoms after bee sting.

Effect of additional vitamin E and zinc supplementation on immunological changes in peripartum Sahiwal cows.

PubMed

Chandra, G; Aggarwal, A; Kumar, M; Singh, A K; Sharma, V K; Upadhyay, R C

2014-12-01

This study was conducted to exploit ameliorative effect of additional vitamin E and/or zinc supplementation on immune response of peripartum Sahiwal cows. Thirty-two pregnant dry Sahiwal cows were blocked into four treatment groups (n = 8), namely control, zinc (Zn), vitamin E (Vit E) and zinc + vitamin E (Zn + Vit E). Feeding regimen was same in all the groups except that the Sahiwal cows in the zinc-, vitamin E- and zinc + vitamin E-fed groups were additionally supplemented with 60 mg Zn/kg DM, 1000 IU vitamin E and 60 mg/kg + 1000 IU Zn + vitamin E, respectively, from day 60 pre-partum to day 90 post-partum. Blood samples were collected on days -60, -45, -30, -15, -7, -3, 0, 3, 7, 15, 30, 45, 60, 90 and 120 with respect to day of parturition and analysed for total immunoglobulin (TIG), immunoglobulin G (IgG), interleukin-2 (IL-2), vitamin E (Vit E) and zinc (Zn) status. Before calving, cows showed a decrease in plasma TIG, IgG, IL-2, Vit E and Zn levels. However, increased levels of plasma TIG, IgG, IL-2, Vit E and Zn were observed after calving. After calving, Sahiwal cows supplemented with Zn + Vit E had higher plasma TIG, IgG and IL-2 in comparison with cows of control and Zn + Vit E-fed groups. In the present study, plasma vitamin E level was higher in Vit E-fed and Zn + Vit E-fed cows; however, zinc level was higher in Zn- and Zn + Vit E-supplemented cows. In conclusion, a reduced immune response during peripartum period in Sahiwal cows was ameliorated by dietary vitamin E and zinc supplementation. Journal of Animal Physiology and Animal Nutrition © 2014 Blackwell Verlag GmbH.

Human Antibody Response to Aedes aegypti Saliva in an Urban Population in Bolivia: A New Biomarker of Exposure to Dengue Vector Bites

PubMed Central

Doucoure, Souleymane; Mouchet, François; Cournil, Amandine; Le Goff, Gilbert; Cornelie, Sylvie; Roca, Yelin; Giraldez, Mabel Guerra; Simon, Zaira Barja; Loayza, Roxanna; Misse, Dorothée; Flores, Jorge Vargas; Walter, Annie; Rogier, Christophe; Herve, Jean Pierre; Remoue, Franck

2012-01-01

Aedes mosquitoes are important vectors of re-emerging diseases in developing countries, and increasing exposure to Aedes in the developed world is currently a source of concern. Given the limitations of current entomologic methods, there is a need for a new effective way for evaluating Aedes exposure. Our objective was to evaluate specific antibody responses to Aedes aegypti saliva as a biomarker for vector exposure in a dengue-endemic urban area. IgG responses to saliva were strong in young children and steadily waned with age. Specific IgG levels were significantly higher in persons living in sites with higher Ae. aegypti density, as measured by using entomologic parameters. Logistic regression showed a significant correlation between IgG to saliva and exposure level, independently of either age or sex. These results suggest that antibody responses to saliva could be used to monitor human exposure to Aedes bites. PMID:22848099

Serum, uterine, and vaginal mucosal IgG antibody responses against Tritrichomonas foetus after administration of a commercial killed whole T foetus vaccine in beef cows.

PubMed

Palomares, R A; Hurley, D J; Crum, L T; Rollin, E; Collop, T; Williard, A; Felton, J; Parrish, J; Corbeil, L B

2017-01-01

The objective of this study was to determine the level and duration of IgG antibodies induced against killed whole Tritrichomonas foetus and T foetus-purified surface antigen (TF1.17) in serum, vaginal, and uterine secretions after systemic immunization of beef cows with a vaccine containing killed whole T foetus. Twenty nonpregnant beef cows were randomly assigned to vaccine or control groups as follows: Vaccine (n = 10): cows received 2 mL of a commercial vaccine containing killed whole T foetus subcutaneously and a 2-mL booster 2 weeks later. Control (n = 10): cows received 2 mL of sterile saline on the same schedule. Vaginal secretions and blood samples were collected on Days 0, 8, 15, 22, 29, 36, 43, 50, 60, 75, 89, 110, 146, and 182 relative to day of primary vaccination. Uterine flush fluid was collected on Days 0, 15, 29, and 43 after the day of primary vaccination. Samples were assayed for IgG antibodies to the killed whole T foetus and surface antigen TF1.17 using enzyme-linked immunosorbent assay. Serum whole T foetus-specific IgG levels were significantly increased (between Days 15 and 182) following vaccination with T foetus or with saline. No differences between vaccinates and controls in uterine responses to whole-cell antigen were detected. Serum anti-TF1.17 IgG responses to vaccination were significantly higher than Day 0 throughout the immunization period (P < 0.001) and were higher than responses in control animals on each day post immunization through Day 146 (P < 0.001). A significant rise in TF1.17-specific IgG levels was observed in vaginal and uterine fluids from Day 15 post vaccination compared to the Day 0 levels. These levels remained significantly elevated in vaginal and uterine fluids through Days 75 (P < 0.05) and 43 (P < 0.001) after primary vaccination, respectively. Antibody levels in serum, vaginal, and uterine secretions against TF1.17 remained low in the control group throughout the study. In conclusion, vaccination of beef cows with a commercial vaccine containing T foetus induced significant increase in the levels of IgG to the T foetus TF1.17 surface antigen in serum, vaginal secretions, and uterine fluid, which remained elevated through Days 43, 75, and 182 in uterine fluids, vaginal secretions, and serum, respectively. Since purified TF1.17 antigen has been shown to protect against experimental T foetus infection in heifers, the vaccine-induced TF1.17-specific IgG response is likely to be important in the prevention of trichomoniasis in beef cattle. Copyright © 2016 Elsevier Inc. All rights reserved.

The Vi conjugate typhoid vaccine is safe, elicits protective levels of IgG anti-Vi, and is compatible with routine infant vaccines.

PubMed

Thiem, Vu Dinh; Lin, Feng-Ying C; Canh, Do Gia; Son, Nguyen Hong; Anh, Dang Duc; Mao, Nguyen Duc; Chu, Chiayung; Hunt, Steven W; Robbins, John B; Schneerson, Rachel; Szu, Shousun C

2011-05-01

Typhoid fever remains a serious problem in developing countries. Current vaccines are licensed for individuals who are 5 years old or older. A conjugate of the capsular polysaccharide (CP) of Salmonella enterica serovar Typhi (Vi) bound to recombinant exoprotein A of Pseudomonas aeruginosa (Vi-rEPA) enhanced Vi immunogenicity and protected 2- to 5-year-olds in Vietnam. In this study, Vi-rEPA was evaluated for use in infants. A total of 301 full-term Vietnamese infants received Expanded Program on Immunization (EPI) vaccines alone or with Vi-rEPA or Haemophilus influenzae type b-tetanus toxoid conjugate (Hib-TT) at 2, 4, and 6 months and Vi-rEPA or Hib-TT alone at 12 months. Infants were visited 6, 24, and 48 h after each injection to monitor adverse reactions. Maternal, cord, and infant sera were assayed for IgG anti-Vi and for IgG antibodies to Hib CP and the diphtheria, tetanus, and pertussis toxins at 7, 12, and 13 months. No vaccine-related serious adverse reactions occurred. In the Vi-rEPA group, the IgG anti-Vi geometric mean (GM) increased from the cord level of 0.66 to 17.4 enzyme-linked immunosorbent assay units (EU) at 7 months, declined to 4.76 EU at 12 months, and increased to 50.1 EU 1 month after the 4th dose (95% of infants had levels of ≥ 3.5 EU, the estimated protective level). Controls had no increase of the IgG anti-Vi GM. Infants with cord anti-Vi levels of <3.5 EU responded with significantly higher IgG anti-Vi levels than those with levels of ≥ 3.5 EU. Anti-diphtheria, -tetanus, and -pertussis toxin levels were similar in all groups. Vi-rEPA was safe, induced protective anti-Vi levels, and was compatible with EPI vaccines, and it can be used in infants. High cord IgG anti-Vi levels partially suppressed infant responses to Vi-rEPA.

Serum Immunoglobulins in Newborn Calves Before and After Colostrum Feeding

PubMed Central

Merriman, Mohendra J. G. S.

1971-01-01

Pre-colostral and post-colostral sera of seven Holstein calves and colostral whey were analyzed immunoelectrophoretically. IgM, IgG1 (fast), and IgG2 (slow) were demonstrated while IgA was not detected in serum of new-born calves before colostrum feeding. In post-colostral serum IgG, IgM, in relatively higher levels, and IgA were present which corresponded with the classes of immunoglobulins found in whey. These observations suggest that the developing bovine fetus may be capable of independent immune response. ImagesFig. 1.Fig. 2.Fig. 3.Fig. 4. PMID:4260939

[Specific humoral immunity after single immunization with mumps vaccine: data of a 3-year follow-up].

PubMed

Otrashevskaia, A V; Bukin, E K; Krasil'nikov, I V; Ignat'ev, G M

2011-01-01

The level and spectrum of humoral specific immunity were studied in 60 volunteers immunized with Russian mumps vaccine. Specific IgG levels were measured by enzyme immunoassay (EIA) and neutralization test using the Leningrad-3 (L-3) mumps virus (MV) vaccine strain and 5 heterologous MV strains of various genotypes (A, B, C, D, and H). The maximum functional activity of antibodies was recorded at an average of 18 months postvaccination. Within 3 years after vaccination, starting at 6 months, specific IgG neutralized all 6 MV strains having varying activity in relation to the genotype. Neutralizing titers (NT) against the L-3 strain were 1.3-1.7-fold higher than those against heterologous MV strains throughout the follow-up. Despite a tendency towards lower specific IgG levels, within 3 years postvaccination, EIA IgG titers remained to be 2.5 -log, L-3 strain HT were -log, or more, and the titers against 5 heterologous MV strains were 2 -log2 or more in all the volunteers.

Humoral and cellular responses to casein in patients with food protein-induced enterocolitis to cow's milk.

PubMed

Caubet, Jean Christoph; Bencharitiwong, Ramon; Ross, Andrew; Sampson, Hugh A; Berin, M Cecilia; Nowak-Węgrzyn, Anna

2017-02-01

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy manifesting within 1 to 4 hours of food ingestion with repetitive emesis and lethargy. We sought to characterize immune responses to casein in children with FPIES caused by cow's milk (CM). Total IgE and IgM, CM-specific IgG, and casein-specific IgE, IgG, IgG 4 , and IgM levels, as well as immunoglobulin free light chains, were measured in both patients with active and those with resolved CM-FPIES. Proliferating casein/T-effector cell counts were measured in children with CM-FPIES, children with IgE-mediated CM allergy, and those tolerating CM. Cytokine concentrations in the supernatants were quantified. Serum cytokine and tryptase levels were measured before and after a positive oral food challenge (OFC) result and compared with levels in those with a negative OFC result. We found low levels of CM and casein-specific IgG and casein-specific IgG 4 in patients with CM-FPIES versus those tolerating CM (P < .05). Although we found both a high CD4 + T cell-proliferative response and T H 2 cytokines production after casein stimulation in children with CM-FPIES, results were similar to those in control subjects. Significantly lower secretion of IL-10 and higher secretion of IL-9 by casein-stimulated T cells were found in patients with CM-FPIES versus those with IgE-mediated CM allergy. Lower baseline serum levels of IL-10 and higher tryptase levels were found in active CM-FPIES versus resolved CM-FPIES. We found a significant increase in serum IL-10 and IL-8 levels after a positive OFC result. We confirm the paucity of humoral response in patients with CM-FPIES. IL-10 might play a key role in acquisition of tolerance in patients with CM-FPIES. Increased serum IL-8 levels in patients with active FPIES suggest neutrophil involvement. Elevated baseline serum tryptase levels in patients with active FPIES suggest low-grade intestinal mast cell activation or increased mast cell load. Copyright © 2016. Published by Elsevier Inc.

Meningococcal serogroup C immunogenicity, antibody persistence and memory B-cells induced by the monovalent meningococcal serogroup C versus quadrivalent meningococcal serogroup ACWY conjugate booster vaccine: A randomized controlled trial.

PubMed

van Ravenhorst, Mariëtte B; van der Klis, Fiona R M; van Rooijen, Debbie M; Knol, Mirjam J; Stoof, Susanne P; Sanders, Elisabeth A M; Berbers, Guy A M

2017-08-24

Adolescents are considered the key transmitters of meningococci in the population. Meningococcal serogroup C (MenC) antibody levels wane rapidly after MenC conjugate vaccination in young children, leaving adolescents with low antibody levels. In this study, we compared MenC immune responses after booster vaccination in adolescence with either tetanus toxoid conjugated MenC (MenC-TT) or MenACWY (MenACWY-TT) vaccine, and aimed to establish an optimal age for this booster. Healthy 10-, 12-, and 15-year-olds, who received a single dose of MenC-TT vaccine in early childhood, were randomized to receive MenC-TT or MenACWY-TT vaccine. MenC serum bactericidal antibody (rSBA) titers, MenC polysaccharide (PS) specific IgG, IgG1 and IgG2 and MenC-specific IgG and IgA memory B-cells were determined before, one month and one year after the booster. Non-inferiority was tested by comparing geometric mean titers (GMTs) between vaccinees at one year. Of 501 participants, 464 (92.6%) were included in the 'according to protocol' cohort analysis. At one month, all participants developed high MenC rSBA titers (>24,000 in all groups) and MenC-PS-specific IgG levels. Non-inferiority was not demonstrated one year after the booster with higher MenC GMTs after the monovalent vaccine, but 462/464 (99.6%) participants maintained protective MenC rSBA titers. IgG levels mainly consisted of IgG1, but similar levels of increase were observed for IgG1 and IgG2. Both vaccines induced a clear increase in the number of circulating MenC-PS specific IgG and IgA memory B-cells. Between one month and one year, the highest antibody decay rate was observed in the 10-year-olds. Both MenC-TT and MenACWY-TT vaccines induced robust protective MenC immune responses after the booster vaccination, although non-inferiority could not be demonstrated for the MenACWY-TT vaccine after one year. Our results underline the importance of optimal timing of a meningococcal booster vaccination to protect against MenC disease in the long-term. Copyright © 2017 Elsevier Ltd. All rights reserved.

Antibody responses to P. falciparum blood stage antigens and incidence of clinical malaria in children living in endemic area in Burkina Faso.

PubMed

Cherif, Mariama K; Ouédraogo, Oumarou; Sanou, Guillaume S; Diarra, Amidou; Ouédraogo, Alphonse; Tiono, Alfred; Cavanagh, David R; Michael, Theisen; Konaté, Amadou T; Watson, Nora L; Sanza, Megan; Dube, Tina J T; Sirima, Sodiomon B; Nebié, Issa

2017-09-08

High parasite-specific antibody levels are generally associated with low susceptibility to Plasmodium falciparum malaria. This has been supported by several studies in which clinical malaria cases of P. falciparum malaria were reported to be associated with low antibody avidities. This study was conducted to evaluate the role of age, malaria transmission intensity and incidence of clinical malaria in the induction of protective humoral immune response against P. falciparum malaria in children living in Burkina Faso. We combined levels of IgG and IgG subclasses responses to P. falciparum antigens: Merozoite Surface Protein 3 (MSP3), Merozoite Surface Protein 2a (MSP2a), Merozoite Surface Protein 2b (MSP2b), Glutamate Rich Protein R0 (GLURP R0) and Glutamate Rich Protein R2 (GLURP R2) in plasma samples from 325 children under five (05) years with age, malaria transmission season and malaria incidence. We notice higher prevalence of P. falciparum infection in low transmission season compared to high malaria transmission season. While, parasite density was lower in low transmission than high transmission season. IgG against all antigens investigated increased with age. High levels of IgG and IgG subclasses to all tested antigens except for GLURP R2 were associated with the intensity of malaria transmission. IgG to MSP3, MSP2b, GLURP R2 and GLURP R0 were associated with low incidence of malaria. All IgG subclasses were associated with low incidence of P. falciparum malaria, but these associations were stronger for cytophilic IgGs. On the basis of the data presented in this study, we conclude that the induction of humoral immune response to tested malaria antigens is related to age, transmission season level and incidence of clinical malaria.

Serum levels of immunoglobulins and severity of community-acquired pneumonia

PubMed Central

de la Torre, Mari C; Torán, Pere; Serra-Prat, Mateu; Palomera, Elisabet; Güell, Estel; Vendrell, Ester; Yébenes, Joan Carles; Torres, Antoni; Almirall, Jordi

2016-01-01

Instruction There is evidence of a relationship between severity of infection and inflammatory response of the immune system. The objective is to assess serum levels of immunoglobulins and to establish its relationship with severity of community-acquired pneumonia (CAP) and clinical outcome. Methods This was an observational and cross-sectional study in which 3 groups of patients diagnosed with CAP were compared: patients treated in the outpatient setting (n=54), patients requiring in-patient care (hospital ward) (n=173), and patients requiring admission to the intensive care unit (ICU) (n=191). Results Serum total IgG (and IgG subclasses IgG1, IgG2, IgG3, IgG4), IgA and IgM were measured at the first clinical visit. Normal cutpoints were defined as the lowest value obtained in controls (≤680, ≤323, ≤154, ≤10, ≤5, ≤30 and ≤50 mg/dL for total IgG, IgG1, IgG2, IgG3, IgG4, IgM and IgA, respectively). Serum immunoglobulin levels decreased in relation to severity of CAP. Low serum levels of total IgG, IgG1 and IgG2 showed a relationship with ICU admission. Low serum level of total IgG was independently associated with ICU admission (OR=2.45, 95% CI 1.4 to 4.2, p=0.002), adjusted by the CURB-65 severity score and comorbidities (chronic respiratory and heart diseases). Low levels of total IgG, IgG1 and IgG2 were significantly associated with 30-day mortality. Conclusions Patients with severe CAP admitted to the ICU showed lower levels of immunoglobulins than non-ICU patients and this increased mortality. PMID:27933180

Humans with chronic granulomatous disease maintain humoral immunologic memory despite low frequencies of circulating memory B cells.

PubMed

Moir, Susan; De Ravin, Suk See; Santich, Brian H; Kim, Jin Young; Posada, Jacqueline G; Ho, Jason; Buckner, Clarisa M; Wang, Wei; Kardava, Lela; Garofalo, Mary; Marciano, Beatriz E; Manischewitz, Jody; King, Lisa R; Khurana, Surender; Chun, Tae-Wook; Golding, Hana; Fauci, Anthony S; Malech, Harry L

2012-12-06

CD27(+) memory B cells are reduced in the blood of patients with chronic granulomatous disease (CGD) for reasons and consequences that remain unclear. Here we confirm not only decreased CD27(+) but also IgG(+) B cells in the blood of CGD patients compared with healthy donors (HDs). However, among IgG(+) B cells, the ratio of CD27(-) to CD27(+) was significantly higher in CGD patients compared with HDs. Similar to conventional memory B cells, CD27(-)IgG(+) B cells of CGD patients expressed activation markers and had undergone somatic hypermutation, albeit at levels lower than their CD27(+) counterparts. Functional analyses revealed slight reductions in frequencies of total IgG but not influenza-specific memory B-cell responses, as measured by Elispot in CGD patients compared with HDs. Serum IgG levels and influenza-specific antibodies were also normal in these CGD patients. Finally, we provide evidence that influenza-specific memory B cells can be present within the CD27(-)IgG(+) B-cell compartment. Together, these findings show that, despite reduced circulating CD27(+) memory B cells, CGD patients maintain an intact humoral immunologic memory, with potential contribution from CD27(-) B cells.

Antibody classes & subclasses induced by mucosal immunization of mice with Streptococcus pyogenes M6 protein & oligodeoxynucleotides containing CpG motifs.

PubMed

Teloni, R; von Hunolstein, C; Mariotti, S; Donati, S; Orefici, G; Nisini, R

2004-05-01

Type-specific antibodies against M protein are critical for human protection as they enhance phagocytosis and are protective. An ideal vaccine for the protection against Streptococcus pyogenes would warrant mucosal immunity, but mucosally administered M-protein has been shown to be poorly immunogenic in animals. We used a recombinant M type 6 protein to immunize mice in the presence of synthetic oligodeoxynucleotides containing CpG motifs (immunostimulatory sequences: ISS) or cholera toxin (CT) to explore its possible usage in a mucosal vaccine. Mice were immunized by intranasal (in) or intradermal (id) administration with four doses at weekly intervals of M6-protein (10 microg/mouse) with or without adjuvant (ISS, 10 microg/mouse or CT, 0,5 microg/mouse). M6 specific antibodies were measured by enzyme linked immunosorbent assay using class and subclass specific monoclonal antibodies. The use of ISS induced an impressive anti M-protein serum IgG response but when id administered was not detectable in the absence of adjuvant. When used in, M-protein in the presence of both ISS and CT induced anti M-protein IgA in the bronchoalveolar lavage, as well as specific IgG in the serum. IgG were able to react with serotype M6 strains of S. pyogenes. The level of antibodies obtained by immunizing mice in with M-protein and CT was higher in comparison to M-protein and ISS. The analysis of anti-M protein specific IgG subclasses showed high levels of IgG1, IgG2a and IgG2b, and low levels of IgG3 when ISS were used as adjuvant. Thus, in the presence of ISS, the ratio IgG2a/IgG1 and (IgG2a+IgG3)/IgG1 >1 indicated a type 1-like response obtained both in mucosally or systemically vaccinated mice. Our study offers a reproducible model of anti-M protein vaccination that could be applied to test new antigenic formulations to induce an anti-group A Streptococcus (GAS) vaccination suitable for protection against the different diseases caused by this bacterium.

Associations of social environment, socioeconomic position and social mobility with immune response in young adults: the Jerusalem Perinatal Family Follow-Up Study.

PubMed

Lawrence, Gabriella M; Friedlander, Yehiel; Calderon-Margalit, Ronit; Enquobahrie, Daniel A; Huang, Jonathan Yinhao; Tracy, Russell P; Manor, Orly; Siscovick, David S; Hochner, Hagit

2017-12-21

Immune response to cytomegalovirus (CMV) impacts adult chronic disease. This study investigates associations of childhood and adulthood social environment, socioeconomic position (SEP) and social mobility with CMV response in young adults. Historical prospective study design. Subcohort of all 17 003 births to residents of Jerusalem between 1974 and 1976. Participants included 1319 young adults born in Jerusalem with extensive archival and follow-up data, including childhood and adulthood SEP-related factors and anti-CMV IgG titre levels and seroprevalence measured at age 32. Principal component analysis was used to transform correlated social environment and SEP-related variables at two time points (childhood and adulthood) into two major scores reflecting household (eg, number of siblings/children, religiosity) and socioeconomic (eg, occupation, education) components. Based on these components, social mobility variables were created. Linear and Poisson regression models were used to investigate associations of components and mobility with anti-CMV IgG titre level and seroprevalence, adjusted for confounders. Lower levels of household and socioeconomic components in either childhood or adulthood were associated with higher anti-CMV IgG titre level and seropositivity at age 32. Compared with individuals with stable favourable components, anti-CMV IgG titre level and risk for seropositivity were higher in stable unfavourable household and socioeconomic components (household: β=3.23, P<0.001; relative risk (RR)=1.21, P<0.001; socioeconomic: β=2.20, P=0.001; RR=1.14, P=0.01), downward household mobility (β=4.32, P<0.001; RR=1.26, P<0.001) and upward socioeconomic mobility (β=1.37, P=0.04; RR=1.19, P<0.001). Among seropositive individuals, associations between household components and mobility with anti-CMV IgG titre level were maintained and associations between socioeconomic components and mobility with anti-CMV IgG titre level were attenuated. Our study provides evidence that accumulating low SEP from childhood through adulthood and social mobility may compromise immune response in young adulthood. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Vaccination with lentiviral vector expressing the nfa1 gene confers a protective immune response to mice infected with Naegleria fowleri.

PubMed

Kim, Jong-Hyun; Sohn, Hae-Jin; Lee, Jinyoung; Yang, Hee-Jong; Chwae, Yong-Joon; Kim, Kyongmin; Park, Sun; Shin, Ho-Joon

2013-07-01

Naegleria fowleri, a pathogenic free-living amoeba, causes fatal primary amoebic meningoencephalitis (PAM) in humans and animals. The nfa1 gene (360 bp), cloned from a cDNA library of N. fowleri, produces a 13.1-kDa recombinant protein which is located on pseudopodia, particularly the food cup structure. The nfa1 gene plays an important role in the pathogenesis of N. fowleri infection. To examine the effect of nfa1 DNA vaccination against N. fowleri infection, we constructed a lentiviral vector (pCDH) expressing the nfa1 gene. For the in vivo mouse study, BALB/c mice were intranasally vaccinated with viral particles of a viral vector expressing the nfa1 gene. To evaluate the effect of vaccination and immune responses of mice, we analyzed the IgG levels (IgG, IgG1, and IgG2a), cytokine induction (interleukin-4 [IL-4] and gamma interferon [IFN-γ]), and survival rates of mice that developed PAM. The levels of both IgG and IgG subclasses (IgG1 and IgG2a) in vaccinated mice were significantly increased. The cytokine analysis showed that vaccinated mice exhibited greater IL-4 and IFN-γ production than the other control groups, suggesting a Th1/Th2 mixed-type immune response. In vaccinated mice, high levels of Nfa1-specific IgG antibodies continued until 12 weeks postvaccination. The mice vaccinated with viral vector expressing the nfa1 gene also exhibited significantly higher survival rates (90%) after challenge with N. fowleri trophozoites. Finally, the nfa1 vaccination effectively induced protective immunity by humoral and cellular immune responses in N. fowleri-infected mice. These results suggest that DNA vaccination using a viral vector may be a potential tool against N. fowleri infection.

Vaccination with Lentiviral Vector Expressing the nfa1 Gene Confers a Protective Immune Response to Mice Infected with Naegleria fowleri

PubMed Central

Kim, Jong-Hyun; Sohn, Hae-Jin; Lee, Jinyoung; Yang, Hee-Jong; Chwae, Yong-Joon; Kim, Kyongmin; Park, Sun

2013-01-01

Naegleria fowleri, a pathogenic free-living amoeba, causes fatal primary amoebic meningoencephalitis (PAM) in humans and animals. The nfa1 gene (360 bp), cloned from a cDNA library of N. fowleri, produces a 13.1-kDa recombinant protein which is located on pseudopodia, particularly the food cup structure. The nfa1 gene plays an important role in the pathogenesis of N. fowleri infection. To examine the effect of nfa1 DNA vaccination against N. fowleri infection, we constructed a lentiviral vector (pCDH) expressing the nfa1 gene. For the in vivo mouse study, BALB/c mice were intranasally vaccinated with viral particles of a viral vector expressing the nfa1 gene. To evaluate the effect of vaccination and immune responses of mice, we analyzed the IgG levels (IgG, IgG1, and IgG2a), cytokine induction (interleukin-4 [IL-4] and gamma interferon [IFN-γ]), and survival rates of mice that developed PAM. The levels of both IgG and IgG subclasses (IgG1 and IgG2a) in vaccinated mice were significantly increased. The cytokine analysis showed that vaccinated mice exhibited greater IL-4 and IFN-γ production than the other control groups, suggesting a Th1/Th2 mixed-type immune response. In vaccinated mice, high levels of Nfa1-specific IgG antibodies continued until 12 weeks postvaccination. The mice vaccinated with viral vector expressing the nfa1 gene also exhibited significantly higher survival rates (90%) after challenge with N. fowleri trophozoites. Finally, the nfa1 vaccination effectively induced protective immunity by humoral and cellular immune responses in N. fowleri-infected mice. These results suggest that DNA vaccination using a viral vector may be a potential tool against N. fowleri infection. PMID:23677321

Seroepidemiology of Helicobacter pylori Infection in Tepehuanos Aged 15 Years and Older in Durango, Mexico

PubMed Central

Alvarado-Esquivel, Cosme

2013-01-01

This study aimed to determine the seroepidemiology of Helicobacter pylori infection in Tepehuanos (an indigenous ethnic group living in rural Mexico). The prevalence of anti-Helicobacter pylori IgG antibodies was examined in 156 Tepehuanos in Durango State, Mexico, using an enzyme-linked immunoassay. In addition, sociodemographic, clinical, and behavioral characteristics of Tepehuanos associated with seropositivity were investigated. In total, 103 (66%) of the 156 participants (mean age 31.03  ±  16.71 years) had Helicobacter pylori IgG antibodies. Fifty-four (52.4%) of the 103 seropositive individuals had Helicobacter pylori IgG antibody levels higher than 100 U/mL. Males and females had comparable seroprevalence of Helicobacter pylori infection and Helicobacter pylori IgG antibody levels. The seroprevalence was significantly higher in women with pregnancies than those without this obstetric characteristic. Logistic regression showed that Helicobacter pylori infection was positively associated with low education (OR = 3.37; 95% CI: 1.13–10.00; P = 0.02) and laborer occupation (OR = 2.71; 95% CI: 1.14–6.42; P = 0.02). This is the first report of seroprevalence and contributing factors for Helicobacter pylori infection in Tepehuanos and of the association of Helicobacter pylori infection with laborer occupation. Results warrants further research. PMID:23577260

Seroepidemiology of Helicobacter pylori Infection in Tepehuanos Aged 15 Years and Older in Durango, Mexico.

PubMed

Alvarado-Esquivel, Cosme

2013-01-01

This study aimed to determine the seroepidemiology of Helicobacter pylori infection in Tepehuanos (an indigenous ethnic group living in rural Mexico). The prevalence of anti-Helicobacter pylori IgG antibodies was examined in 156 Tepehuanos in Durango State, Mexico, using an enzyme-linked immunoassay. In addition, sociodemographic, clinical, and behavioral characteristics of Tepehuanos associated with seropositivity were investigated. In total, 103 (66%) of the 156 participants (mean age 31.03  ±  16.71 years) had Helicobacter pylori IgG antibodies. Fifty-four (52.4%) of the 103 seropositive individuals had Helicobacter pylori IgG antibody levels higher than 100 U/mL. Males and females had comparable seroprevalence of Helicobacter pylori infection and Helicobacter pylori IgG antibody levels. The seroprevalence was significantly higher in women with pregnancies than those without this obstetric characteristic. Logistic regression showed that Helicobacter pylori infection was positively associated with low education (OR = 3.37; 95% CI: 1.13-10.00; P = 0.02) and laborer occupation (OR = 2.71; 95% CI: 1.14-6.42; P = 0.02). This is the first report of seroprevalence and contributing factors for Helicobacter pylori infection in Tepehuanos and of the association of Helicobacter pylori infection with laborer occupation. Results warrants further research.

IgE low affinity receptor (CD23) expression, Plasmodium falciparum specific IgE and tumor necrosis factor-alpha production in Thai uncomplicated and severe falciparum malaria patients.

PubMed

Kumsiri, Ratchanok; Troye-Blomberg, Marita; Pattanapanyasat, Kovit; Krudsood, Srivicha; Maneerat, Yaowapa

2016-02-01

Previous studies have suggested that Plasmodium falciparum (P. falciparum) specific IgE in the form of immune complexes crosslinking the low-affinity receptor (CD23) on monocyte results in tumor necrosis factor (TNF)-α and nitric oxide (NO) production. However, the roles of these parameters in severity and immune protection are still unclear. This study aimed to determine the association between CD23 expression on monocytes, plasma soluble CD23 (sCD23), total IgE, malaria-specific IgE and IgG, and TNF-α levels in P. falciparum infected patients. We evaluated 64 uncomplicated (UC) and 25 severe patients (S), admitted at the Hospital for Tropical Diseases, Mahidol University, and 34 healthy controls (C) enrolled in 2001. Flow cytometry and enzyme linked immunosorbent assays (ELISA) demonstrated that trends of the CD23 expression, levels of sCD23 and specific IgE were higher in the S group as compared to those in the UC and C groups. Plasma levels of P. falciparum specific IgE in the UC (p=0.011) and S groups (p=0.025) were significantly higher than those in C group. In contrast the TNF-α levels tended to be higher in the UC than those in the S (p=0.343) and significantly higher than those in C (p=0.004) groups. The specific IgG levels in UC were significantly higher than those in S and C (p<0.001) groups. At admission, a strong significant negative correlation was found between specific IgG and sCD23 (r=-0.762, p=0.028), and TNF-α and IgE-IgG complexes (r=-0.715, p=0.002). Significant positive correlations between levels of specific IgE and TNF-α (r=0.575, p=0.010); and sCD23 (r=0.597, p=0.000) were also observed. In conclusion, our data suggest that CD23 expression and malaria-specific IgE levels may be involved in the severity of the disease while TNF-α and the malaria-specific IgG may correlate with protection against falciparum malaria. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Serum IgG subclass levels and risk of exacerbations and hospitalizations in patients with COPD.

PubMed

Leitao Filho, Fernando Sergio; Ra, Seung Won; Mattman, Andre; Schellenberg, Robert S; Criner, Gerard J; Woodruff, Prescott G; Lazarus, Stephen C; Albert, Richard; Connett, John E; Han, Meilan K; Martinez, Fernando J; Leung, Janice M; Paul Man, S F; Aaron, Shawn D; Reed, Robert M; Sin, Don D

2018-02-14

The literature is scarce regarding the prevalence and clinical impact of IgG subclass deficiency in COPD. We investigated the prevalence of IgG subclass deficiencies and their association with exacerbations and hospitalizations using subjects from two COPD cohorts. We measured IgG subclass levels using immunonephelometry in serum samples from participants enrolled in two previous COPD trials: Macrolide Azithromycin for Prevention of Exacerbations of COPD (MACRO; n = 976) and Simvastatin for the Prevention of Exacerbations in Moderate-to-Severe COPD (STATCOPE; n = 653). All samples were collected from clinically stable participants upon entry into both studies. IgG subclass deficiency was diagnosed when IgG subclass levels were below their respective lower limit of normal: IgG1 < 2.8 g/L; IgG2 < 1.15 g/L; IgG3 < 0.24 g/L; and IgG4 < 0.052 g/L. To investigate the impact of IgG subclass levels on time to first exacerbation or hospitalization, we log-transformed IgG levels and performed Cox regression models, with adjustments for confounders. One or more IgG subclass deficiencies were found in 173 (17.7%) and 133 (20.4%) participants in MACRO and STATCOPE, respectively. Lower IgG1 or IgG2 levels resulted in increased risk of exacerbations with adjusted hazard ratios (HR) of 1.30 (95% CI, 1.10-1.54, p < 0.01) and 1.19 (95% CI, 1.05-1.35, p < 0.01), respectively in the MACRO study, with STATCOPE yielding similar results. Reduced IgG1 or IgG2 levels were also associated with increased risk of hospitalizations: the adjusted HR for IgG1 and IgG2 was 1.52 (95% CI: 1.15-2.02, p < 0.01) and 1.33 (95% CI, 1.08-1.64, p < 0.01), respectively for the MACRO study; in STATCOPE, only IgG2 was an independent predictor of hospitalization. In our multivariate Cox models, IgG3 and IgG4 levels did not result in significant associations for both outcomes in either MACRO or STATCOPE cohorts. Approximately 1 in 5 COPD patients had one or more IgG subclass deficiencies. Reduced IgG subclass levels were independent risk factors for both COPD exacerbations (IgG1 and IgG2) and hospitalizations (IgG2) in two COPD cohorts. This study used serum samples from participants of the MACRO ( NCT00325897 ) and STATCOPE ( NCT01061671 ) trials.

Value of serum IgG4 in the diagnosis of IgG4-related disease and in differentiation from rheumatic diseases and other diseases.

PubMed

Yamamoto, Motohisa; Tabeya, Tetsuya; Naishiro, Yasuyoshi; Yajima, Hidetaka; Ishigami, Keisuke; Shimizu, Yui; Obara, Mikiko; Suzuki, Chisako; Yamashita, Kentaro; Yamamoto, Hiroyuki; Hayashi, Toshiaki; Sasaki, Shigeru; Sugaya, Toshiaki; Ishida, Tadao; Takano, Ken-Ichi; Himi, Tetsuo; Suzuki, Yasuo; Nishimoto, Norihiro; Honda, Saho; Takahashi, Hiroki; Imai, Kohzoh; Shinomura, Yasuhisa

2012-06-01

IgG4-related disease (IgG4-RD) is a novel disease entity that includes Mikulicz's disease, autoimmune pancreatitis (AIP), and many other conditions. It is characterized by elevated serum IgG4 levels and abundant IgG4-bearing plasmacyte infiltration of involved organs. We postulated that high levels of serum IgG4 would comprise a useful diagnostic tool, but little information is available about IgG4 in conditions other than IgG4-RD, including rheumatic diseases. Several reports have described cutoff values for serum IgG4 when diagnosing IgG4-RD, but these studies mostly used 135 mg/dL in AIP to differentiate from pancreatic cancer instead of rheumatic and other common diseases. There is no evidence for a cutoff serum IgG4 level of 135 mg/dL for rheumatic diseases and common diseases that are often complicated with rheumatic diseases. The aim of this work was to re-evaluate the usual cutoff serum IgG4 value in AIP (135 mg/dL) that is used to diagnose whole IgG4-RD in the setting of a rheumatic clinic by measuring serum IgG4 levels in IgG4-RD and various disorders. We therefore constructed ROC curves of serum IgG4 levels in 418 patients who attended Sapporo Medical University Hospital due to IgG4-RD and various rheumatic and common disorders. The optimal cut-off value of serum IgG4 for a diagnosis of IgG4-RD was 144 mg/dL, and the sensitivity and specificity were 95.10 and 90.76%, respectively. Levels of serum IgG4 were elevated in IgG4-RD, Churg-Strauss syndrome, multicentric Castleman's disease, eosinophilic disorders, and in some patients with rheumatoid arthritis, systemic sclerosis, chronic hepatitis, and liver cirrhosis. The usual cut-off value of 135 mg/dL in AIP is useful for diagnosing whole IgG4-RD, but high levels of serum IgG4 are sometimes observed in not only IgG4-RD but also other rheumatic and common diseases.

Oral Immunization with Recombinant Norwalk Virus-Like Particles Induces a Systemic and Mucosal Immune Response in Mice

PubMed Central

Ball, Judith M.; Hardy, Michele E.; Atmar, Robert L.; Conner, Margaret E.; Estes, Mary K.

1998-01-01

Recombinant Norwalk virus-like particles (rNV VLPs) produced in insect cells were evaluated as an oral immunogen in CD1 and BALB/c mice by monitoring rNV-specific serum total and subclass immunoglobulin G (IgG) and intestinal IgA responses. Dose and kinetics of response were evaluated in the presence and absence of the mucosal adjuvant cholera toxin (CT). rNV-specific serum IgG and intestinal IgA were detected in the absence of CT, and the number of responders was not significantly different from that of mice administered VLPs with CT at most doses. The use of CT was associated with induction of higher levels of IgG in serum; this effect was greater at higher doses of VLPs. IgG in serum was detected in the majority of animals by 9 days postimmunization (dpi), and intestinal IgA responses were detected by 24 dpi. In the absence of CT, IgG2b was the dominant IgG subclass response in both mouse strains. Thus, nonreplicating rNV VLPs are immunogenic when administered orally in the absence of any delivery system or mucosal adjuvant. These studies demonstrate that rNV VLPs are an excellent model to study the oral delivery of antigen, and they are a potential mucosal vaccine for NV infections. PMID:9445035

Microproteinuria during Opisthorchis viverrini Infection: A Biomarker for Advanced Renal and Hepatobiliary Pathologies from Chronic Opisthorchiasis

PubMed Central

Saichua, Prasert; Sithithaworn, Paiboon; Jariwala, Amar R.; Deimert, David J.; Sithithaworn, Jiraporn; Sripa, Banchob; Laha, Thewarach; Mairiang, Eimorn; Pairojkul, Chawalit; Periago, Maria Victoria; Khuntikeo, Narong; Mulvenna, Jason; Bethony, Jeffrey M.

2013-01-01

Approximately 680 million people are at risk of infection with Opisthorchis viverrini (OV) and Clonorchis sinensis, with an estimated 10 million infected with OV in Southeast Asia alone. While opisthorchiasis is associated with hepatobiliary pathologies, such as advanced periductal fibrosis (APF) and cholangiocarcinoma (CCA), animal models of OV infection show that immune-complex glomerulonephritis is an important renal pathology that develops simultaneously with hepatobiliary pathologies. A cardinal sign of immune-complex glomerulonephritis is the urinary excretion of immunoglobulin G (IgG) (microproteinuria). In community-based studies in OV endemic areas along the Chi River in northeastern Thailand, we observed that over half of the participants had urine IgG against a crude OV antigen extract (OV antigen). We also observed that elevated levels of urine IgG to OV antigen were not associated with the intensity of OV infection, but were likely the result of immune-complex glomerulonephritis as seen in animal models of OV infection. Moreover, we observed that urine IgG to OV antigen was excreted at concentrations 21 times higher in individuals with APF and 158 times higher in individuals with CCA than controls. We also observed that elevated urine IgG to OV antigen could identify APF+ and CCA+ individuals from non-cases. Finally, individuals with urine IgG to OV antigen had a greater risk of APF as determined by Odds Ratios (OR = 6.69; 95%CI: 2.87, 15.58) and a greater risk of CCA (OR = 71.13; 95%CI: 15.13, 334.0) than individuals with no detectable level of urine IgG to OV antigen. Herein, we show for the first time the extensive burden of renal pathology in OV endemic areas and that a urine biomarker could serve to estimate risk for both renal and hepatobiliary pathologies during OV infection, i.e., serve as a “syndromic biomarker” of the advanced pathologies from opisthorchiasis. PMID:23717698

Protection against Fasciola gigantica infection in mice by vaccination with recombinant juvenile-specific cathepsin L.

PubMed

Sansri, Veerawat; Meemon, Krai; Changklungmoa, Narin; Kueakhai, Pornanan; Chantree, Pathanin; Chaichanasak, Pannigan; Lorsuwannarat, Natcha; Itagaki, Tadashi; Sobhon, Prasert

2015-03-24

Fasciola gigantica cathepsin L1H (FgCatL1H) is one of the major cathepsin L released by juveniles of F. gigantica to aid in the invasion of host's tissues. Due to its high sequence similarity with other cathepsin L (CatL) isoforms of late stage F. gigantica, it was considered to be a good vaccine candidate that can block all CatL-mediated protease activities and affect juveniles as well as adult parasites. In this study, recombinant proFgCatL1H protein expressed in yeast, Pichia pastoris, system was mixed with Freund's adjuvants and used to subcutaneously immunize mice that were later challenged with metacercariae of F. gigantica. The percentage of worm protection in the rproFgCatL1H-vaccinated mice compared to the non-immunized and adjuvant control mice were approximately 62.7% and 66.1%, respectively. Anti-rproFgCatL1H antisera collected from vaccinated mice reacted specifically with rproFgCatL1H and other cathepsin L isoforms of F. gigantica, but the antibodies did not cross react with antigens from other trematode and nematode parasites, including Eurytrema pancreaticum, Opisthorchis viverrini, Fischoederius cobboldi, Cotylophoron cotylophorum, Gigantocotyle explanatum, Paramphistomum cervi, and Setaria labiato-papillosa. The levels of IgG1 and IgG2a in mouse sera increased significantly at two weeks after immunization and were highest during the sixth to eighth weeks after immunization. The IgG1 level was higher than IgG2a at all periods of immunization, implicating the dominance of the Th2 response. The levels of IgG1 and IgG2a in the immune sera were shown to be strongly correlated with the numbers of worm recovery, and the correlation coefficient was higher for IgG1. The levels of serum aspartate aminotransferase and alanine transaminase were significantly lower in the sera of rproFgCatL1H-vaccinated mice than in the infected control mice indicating a lower degree of liver damage. This study demonstrated a high potential of FgCatL1H vaccine, and its efficacy is currently being studied in the larger economic animals. Copyright © 2015 Elsevier Ltd. All rights reserved.

IgM, IgG and IgA rheumatoid factors and circulating immune complexes in patients with AIDS and AIDS-related complex with serological abnormalities.

PubMed Central

Procaccia, S; Lazzarin, A; Colucci, A; Gasparini, A; Forcellini, P; Lanzanova, D; Foppa, C U; Novati, R; Zanussi, C

1987-01-01

To investigate some humoral aspects which may reflect the involvement of B lymphocytes in the acquired immunodeficiency syndrome (AIDS), we used an enzyme-linked immunoassay (ELISA) to determine the levels of IgM, IgG and IgA rheumatoid factors (RF) in 16 patients suffering from full-blown AIDS and 32 patients with AIDS-related complex (ARC), in the clinical form of lymphoadenopathy syndrome (LAS), compared with 40 healthy, young heterosexual subjects. Both AIDS and ARC patients showed a greater incidence of high IgM RF levels, with mean values significantly higher than controls, but with no differences between the two pathological groups. IgG RF behaviour was similar in the two patient populations and the healthy subjects. IgA RF were significantly raised in AIDS and ARC. Further information on RF was obtained by determination of the immunoglobulin levels of the respective isotypes in the same patients. Mean IgG levels were above normal in AIDS and ARC patients, but the latter group showed a higher incidence of increased values and higher mean levels. The IgA isotype was significantly increased mainly in AIDS patients. The behaviour of IgM was virtually the same in the three groups studied. A difference between AIDS and ARC patients was established by the detection of circulating immune-complexes (IC) by the C1q-binding and CIC-conglutinin assays. IC were significantly high, by both methods, only in the ARC group, but normal or very low in AIDS. These overall findings suggest once again the impairment of B cell function in AIDS, with prevalent hyperactivation in ARC and exhaustion in full-blown AIDS, and apparent preservation, in the latter group, of the antibody responses which are more closely related to the activity of subsets of T helper cells. PMID:3608224

Self-perceived oral health and salivary proteins in children with type 1 diabetes.

PubMed

Javed, F; Sundin, U; Altamash, M; Klinge, B; Engström, P-E

2009-01-01

The aim was to validate self-perceived oral health with salivary IgG as an inflammatory parameter in children with type 1 diabetes. Unstimulated whole saliva samples were collected from 36 children with well controlled and 12 with poorly controlled type 1 diabetes and 40 non-diabetic children (Controls). Salivary flow rate, random blood glucose level, salivary protein concentration and immunoglobulin A and G levels were recorded using standard techniques. Data concerning oral health and diabetes status were collected. Self-perceived gingival bleeding (bleeding gums), bad breath and dry mouth were higher in diabetic children when compared with those in controls (P < 0.05). Gingival bleeding was frequently perceived by children with poorly controlled compared to well-controlled type 1 diabetes (P < 0.05) and controls (P < 0.001). Bad breath was common perceived by children with poorly controlled compared to well-controlled type 1 diabetes (P < 0.05) and controls (P < 0.0001). Salivary flow rate was lower in the diabetic children compared to controls (P < 0.01) with no difference between children with poorly controlled and well-controlled type 1 diabetes. Salivary IgG per mg protein concentration was higher in the diabetics when compared with the control group (P < 0.0001). IgG per mg protein levels were also higher in children with poorly controlled when compared with well-controlled type 1 diabetes (P < 0.05). There was no difference in IgA per mg protein and total protein concentrations between children with poorly controlled and well-controlled type 1 diabetes. Self-perceived gingival bleeding and salivary IgG per mg protein concentration were increased in children with type 1 diabetes compared with controls. These variables were also increased in children with poorly controlled compared with well-controlled type 1 diabetes.

Serum levels of IgG and IgG4 in Hashimoto thyroiditis.

PubMed

Kawashima, Sachiko-Tsukamoto; Tagami, Tetsuya; Nakao, Kanako; Nanba, Kazutaka; Tamanaha, Tamiko; Usui, Takeshi; Naruse, Mitsuhide; Minamiguchi, Sachiko; Mori, Yusuke; Tsuji, Jun; Tanaka, Issei; Shimatsu, Akira

2014-03-01

Although IgG4-related disease is characterized by extensive infiltration of IgG4-positive plasma cells and lymphocytes of various organs, the details of this systemic disease are still unclear. We screened serum total IgG levels in the patients with Hashimoto thyroiditis (HT) to illustrate the prevalence of IgG4-related thyroiditis in HT. Twenty-four of 94 patients with HT (25.5%) had elevated serum IgG levels and their serum IgG4 was measured. Five of the 24 cases had more than 135 mg/dL of IgG4, which is the serum criterion of IgG4-related disease. One was a female patient who was initially treated as Graves' disease and rapidly developed a firm goiter and hypothyroidism. The biopsy of her thyroid gland revealed that follicular cells were atrophic with squamous metaplasia, replaced with fibrosis, which was compatible with the fibrous variant of HT. Immunohistochemical examination revealed diffuse infiltration of IgG4-positive plasma cells, and the serum IgG4 level was 179 mg/dL. The levels of IgG and IgG4 were positively correlated with the titers of anti-thyroglobulin antibody or anti-thyroid peroxidase antibody. In conclusion, at least a small portion of patients with HT with high titers of anti-thyroid antibodies may overlap the IgG4-related thyroiditis.

Expression of FcRn receptor in placental tissue and its relationship with IgG levels in term and preterm newborns.

PubMed

Lozano, Natalia A; Lozano, Alejandro; Marini, Vanina; Saranz, Ricardo J; Blumberg, Richard S; Baker, Kristi; Agresta, Maria F; Ponzio, Marina F

2018-05-10

IgG is the only antibody class, that is, actively transferred from the mother to the fetus across the placenta by an active, neonatal Fc receptor (FcRn) mediated process during pregnancy, conferring passive immunity and protection against infections to the newborn during the first months of life. Preterm infants may not receive sufficient titers of protective antibodies, as most of them are transferred only after the 34th week of gestation. Because of the great importance of this process, we investigated in a clinical setting the placental transmission of IgG antibodies in term and preterm newborns. This work was conducted in 85 woman and their newborns, divided into four groups according to their clinical gestational age (≤37 weeks were considered as preterm). Blood samples were collected from the mothers and their newborns' umbilical cords to analyze total serum IgG concentrations, and a subgroup of 32 placentas was analyzed by immunohistochemistry to quantify the expression of the FcRn receptor. Total IgG levels in both mothers and neonates increased significantly through the third trimester of gestation. Regarding the newborns, in all groups, IgG levels exceeded their mother's values by a ~2.4%. A higher expression of FcRn was detected in placentas from newborns at week 36 of gestation onwards. Our results obtained from clinical samples, were in line with previous descriptions in model systems and confirmed that the IgG transfer from maternal serum to the fetus is positively correlated with FcRn expression in placental tissue throughout gestation. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Postoperative change of anti-Thomsen-Friedenreich and Tn IgG level: the follow-up study of gastrointestinal cancer patients.

PubMed

Smorodin, Eugeniy-P; Kurtenkov, Oleg-A; Sergeyev, Boris-L; Kodar, Kristel-E; Chuzmarov, Valentin-I; Afanasyev, Vladimir-P

2008-07-21

To study the influence of tumor removal on the serum level of IgG antibodies to tumor-associated Thomsen-Friedenreich (TF), Tn carbohydrate epitopes and xenogeneic alphaGal, and to elucidate on the change of the level during the follow-up as well as its association with the stage and morphology of the tumor and the values of blood parameters in gastrointestinal cancer. Sixty patients with gastric cancer and 34 patients with colorectal cancer in stages I-IV without distant metastases were subjected to follow-up. The level of antibodies in serum was determined by the enzyme-linked immunosorbent assay (ELISA) using synthetic polyacrylamide (PAA) glycoconjugates. Biochemical and haematological analyses were performed using automated equipment. In gastrointestinal cancer, the TF antibody level was found to have elevated significantly after the removal of G3 tumors as compared with the preoperative level (u = 278.5, P < 0.05). After surgery, the TF and Tn antibody level was elevated in the majority of gastric cancer patients (sign test, 20 vs 8, P < 0.05, and 21 vs 8, P < 0.05, respectively). In gastrointestinal cancer, the elevated postoperative level of TF, Tn and alphaGal antibodies was noted in most patients with G3 tumors (sign test, 22 vs 5, P < 0.01; 19 vs 6, P < 0.05; 24 vs 8, P < 0.01, respectively), but the elevation was not significant in patients with G1 + G2 resected tumors. The postoperative follow-up showed that the percentage of patients with G3 resected tumors of the digestive tract, who had a mean level of anti-TF IgG above the cut-off value (1.53), was significantly higher than that of patients with G1 + G2 resected tumors (c2 = 3.89, all patients; c2 = 5.34, patients without regional lymph node metastases; P < 0.05). The percentage of patients with a tumor in stage I, whose mean anti-TF IgG level remained above the cut-off value (1.26), was significantly higher than that of patients with the cancer in stages III-IV (c2 = 4.71, gastric cancer; c2 = 4.11, gastrointestinal cancer; P < 0.05). The correlation was observed to exist between the level of anti-TF IgG and the count of lymphocytes (r = 0.517, P < 0.01), as well as between the level of anti-Tn IgG and that of serum CA 19-9 (r = 0.481, P < 0.05). No positive delayed-type hypersensitivity reaction in skin test challenges with TF-PAA in any of the fifteen patients, including those with a high level of anti-TF IgG, was observed. The surgical operation raises the level of anti-carbohydrate IgG in most patients, especially in those with the G3 tumor of the gastrointestinal tract. The follow-up demonstrates that after surgery the low preoperative level of TF antibodies may be considerably increased in patients with the carcinoma in its early stage but remains low in its terminal stages. The stage- and morphology-dependent immunosuppression affects the TF-antibody response and may be one of the reasons for unresponsiveness to the immunization with TF-antigens.

Toxoplasma gondii Infection in the United States, 2011-2014.

PubMed

Jones, Jeffrey L; Kruszon-Moran, Deanna; Elder, Scott; Rivera, Hilda N; Press, Cindy; Montoya, Jose G; McQuillan, Geraldine M

2018-02-01

Toxoplasma gondii can cause severe neurologic and ocular disease when transmitted congenitally and in immunosuppressed persons. Sera collected in the National Health and Nutrition Examination Survey 2011 through 2014 in 13,507 persons ≥ 6 years old were tested for T. gondii immunoglobulin (Ig) G and IgM antibodies, and in those both IgG and IgM antibody positive, for IgG avidity. Overall, 11.14% (95% confidence limits [CL] 9.88%, 12.51%) were seropositive for T. gondii IgG antibody (age-adjusted seroprevalence 10.42% [95% CL 9.19%, 11.76%]); in women aged 15-44 years, the age-adjusted T. gondii IgG seroprevalence was 7.50% (95% CL 6.00%, 9.25%). In multivariable analysis, risk for IgG seropositivity increased with age and was higher in males; persons living below the poverty level; persons with ≤ a high school education compared with those with > a high school education; and non-Hispanic black, Mexican American, and foreign born non-Hispanic white persons compared with U.S.-born non-Hispanic white persons. Overall, 1.16% (95% CL 0.94%, 1.42%) were T. gondii IgM antibody positive and 0.71%, (95% CL 0.54%, 0.92%) were both IgM and IgG antibody positive. In multivariable analysis, the significant risk factors for being both IgM and IgG positive were older age, crowding, and non-U.S. birth origin compared with U.S.-born persons. Among those positive for both IgM and IgG antibody, almost all had high avidity (all women aged 15-44 years had high avidity). Toxoplasma gondii antibody prevalence remains relatively low in the United States, although it is higher in non-U.S.-born persons, males, and some minority and socioeconomically disadvantaged groups.

An observational clinical case of Zika virus-associated neurological disease is associated with primary IgG response and enhanced TNF levels.

PubMed

Delatorre, Edson; Miranda, Milene; Tschoeke, Diogo A; Carvalho de Sequeira, Patrícia; Alves Sampaio, Simone; Barbosa-Lima, Giselle; Rangel Vieira, Yasmine; Leomil, Luciana; Bozza, Fernando A; Cerbino-Neto, José; Bozza, Patricia T; Ribeiro Nogueira, Rita Maria; Brasil, Patrícia; Thompson, Fabiano L; de Filippis, Ana M B; Souza, Thiago Moreno L

2018-05-17

Descriptive clinical data help to reveal factors that may provoke Zika virus (ZIKV) neuropathology. The case of a 24-year-old female with a ZIKV-associated severe acute neurological disorder was studied. The levels of ZIKV in the cerebrospinal fluid (CSF) were 50 times higher than the levels in other compartments. An acute anti-flavivirus IgG, together with enhanced TNF-alpha levels, may have contributed to ZIKV invasion in the CSF, whereas the unbiased genome sequencing [obtained by next-generation sequencing (NGS)] of the CSF revealed that no virus mutations were associated with the anatomic compartments (CSF, serum, saliva and urine).

Alterations in IgG subclasses in acquired immune deficiency syndrome.

PubMed

Outschoorn, I M; Lluberes, R; Natta, C L

1989-01-01

Decreased IgG subclass levels in pyogenic infections and immunocompromised situations have been described. A study was made to determine IgG subclass levels in four groups of 68 Hispanic patients. The first group consisted of 25 terminal patients with AIDS, the second group of 20 i.v. drug abusers, and the third group of eight hospital patients with neither a diagnosis of AIDS/ARC nor a history of i.v. drug abuse. IgG subclass levels of these 53 cases were compared with those of a fourth group of 15 normal controls. The total IgG, IgA, and IgM levels as well as the four IgG subclass concentrations were measured by radial immunodiffusion using appropriate standards and specific antisera. The first two groups had similar values, with an average IgG level of 10.37 g/liter; IgA, 2.68; and IgM, 1.78; subclass levels were IgG1, 6.68 g/liter; IgG2, 2.77; IgG3, 0.34; and IgG4, 0.68. These were significantly lower than those of controls, except for IgG4. Determination of minor subclasses may offer some possibilities for immunomodulation and therapy and could be useful in terms of prognosis.

Characterization of Alpha-Toxin hla Gene Variants, Alpha-Toxin Expression Levels, and Levels of Antibody to Alpha-Toxin in Hemodialysis and Postsurgical Patients with Staphylococcus aureus Bacteremia

PubMed Central

Wu, Yuling; Tabor, David E.; Mok, Hoyin; Sellman, Bret R.; Jenkins, Amy; Yu, Li; Jafri, Hasan S.; Rude, Thomas H.; Ruffin, Felicia; Schell, Wiley A.; Park, Lawrence P.; Yan, Qin; Thaden, Joshua T.; Messina, Julia A.; Esser, Mark T.

2014-01-01

Alpha-toxin is a major Staphylococcus aureus virulence factor. This study evaluated potential relationships between in vitro alpha-toxin expression of S. aureus bloodstream isolates, anti-alpha-toxin antibody in serum of patients with S. aureus bacteremia (SAB), and clinical outcomes in 100 hemodialysis and 100 postsurgical SAB patients. Isolates underwent spa typing and hla sequencing. Serum anti-alpha-toxin IgG and neutralizing antibody levels were measured by using an enzyme-linked immunosorbent assay and a red blood cell (RBC)-based hemolysis neutralization assay. Neutralization of alpha-toxin by an anti-alpha-toxin monoclonal antibody (MAb MEDI4893) was tested in an RBC-based lysis assay. Most isolates encoded hla (197/200; 98.5%) and expressed alpha-toxin (173/200; 86.5%). In vitro alpha-toxin levels were inversely associated with survival (cure, 2.19 μg/ml, versus failure, 1.09 μg/ml; P < 0.01). Both neutralizing (hemodialysis, 1.26 IU/ml, versus postsurgical, 0.95; P < 0.05) and IgG (hemodialysis, 1.94 IU/ml, versus postsurgical, 1.27; P < 0.05) antibody levels were higher in the hemodialysis population. Antibody levels were also significantly higher in patients infected with alpha-toxin-expressing S. aureus isolates (P < 0.05). Levels of both neutralizing antibodies and IgG were similar among patients who were cured and those not cured (failures). Sequence analysis of hla revealed 12 distinct hla genotypes, and all genotypic variants were susceptible to a neutralizing monoclonal antibody in clinical development (MEDI4893). These data demonstrate that alpha-toxin is highly conserved in clinical S. aureus isolates. Higher in vitro alpha-toxin levels were associated with a positive clinical outcome. Although patients infected with alpha-toxin-producing S. aureus exhibited higher anti-alpha-toxin antibody levels, these levels were not associated with a better clinical outcome in this study. PMID:25392350

Infiltration of peritumoural but tumour-free parenchyma with IgG4-positive plasma cells in hilar cholangiocarcinoma and pancreatic adenocarcinoma.

PubMed

Resheq, Yazid J; Quaas, Alexander; von Renteln, Daniel; Schramm, Christoph; Lohse, Ansgar W; Lüth, Stefan

2013-10-01

Recently, new guidelines for diagnosing IgG4-associated cholangitis have been published devaluing the diagnostic significance of IgG4-positive plasma cells and steroid trials. We sought to evaluate the utility of IgG4-positive plasma cells in discriminating IgG4-associated cholangitis from hilar cholangiocarcinoma and autoimmune pancreatitis from pancreatic adenocarcinoma under conditions when malignancy is likely to be missed. Resection specimens obtained from patients with hilar cholangiocarcinoma, pancreatic adenocarcinoma or hepatocellular carcinoma were re-evaluated for IgG4-positivity. Histological analysis focussed on peritumoural but tumour-free sections. Perioperative biochemical and clinical data were reviewed. Nineteen patients with hilar cholangiocarcinoma and 29 patients with pancreatic adenocarcinoma were eligible for histological re-evaluation. Six of 19 (32%) patients with hilar cholangiocarcinoma and 5 of 29 (17%) patients with pancreatic adenocarcinoma were IgG4-positive (≥20 IgG4-positive plasma cells per high power field). Patients with IgG4-positive hilar cholangiocarcinoma showed significantly higher levels of serum total bilirubin (3.6mg/dl vs. 1.8mg/dl; P<0.05) and serum alanine-aminotransferase (median 343U/l vs. 63U/l, P<0.05) compared to IgG4-negative patients with hilar cholangiocarcinoma. IgG4-positive plasma cells are of limited utility especially in distinguishing hilar cholangiocarcinoma from IgG4-associated cholangitis even when combined with clinical parameters and may be misleading under conditions when malignancy is missed. Copyright © 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Differential expression of immune factor between patients with chronic prostatitis/chronic pelvic pain syndrome and the healthy volunteers.

PubMed

Ye, Chen; Xiao, Guang'an; Xu, Jian; Qin, Shengfei; Luo, Yuhua; Chen, Guanghua; Lai, H Henry; Zhou, Tie

2018-03-01

Immune mechanisms have been hypothesized to contribute to the development of CP/CPPS. In this study, we investigated the differential expression of immune factors between patients with CP/CPPS and healthy volunteers. This study was registered in Australian New Zealand Clinical Trials Registry. Healthy volunteers and patients with CP/CPPS were enrolled in this study. The inclusion criteria for patients were below: (1) aged 18-45 years old; (2) prostatitis-related syndrome longer than 3 months; (3) normal routine urine culture and negative bacterial culture in prostatic fluid. Patients were further classified into two groups: types IIIA and IIIB CP/CPPS according to the results of EPS routine test. Serum immune markers include IgA, IgM, IgG, CD4 + and CD8 + . There are total 23 CP/CPPS patients, including 12 type IIIB and 11 type IIIA. Relatively, there are 26 healthy volunteers. The serum levels of IgG were higher in CP/CPPS patients compared to healthy volunteers (1141.2 ± 204.3 vs 1031.9 ± 173.7 mg/L, p = 0.045), while the serum levels of CD8 + were lower in CP/CPPS patients compared to healthy volunteers (492.8 ± 185.6 vs 640.0 ± 246.8 cells/μL, p = 0.021). Furthermore, serum levels of IgG were higher in patients with IIIA CP/CPPS compared to those with IIIB (1244.3 ± 151.6 vs 1054.3 ± 209.3 mg/L, p = 0.023). Differential levels of IgG and CD8 + between CPPS patients and healthy volunteers suggest a contributing role of immune mechanisms to the development of CP/CPPS; and IgG may play an important role in inflammatory CPPS. Clinical Study registration number ACTRN12613000792729.

[Effect of vitamine A on mice immune response induced by specific periodontal pathogenic bacteria-immunization].

PubMed

Lin, Xiao-Ping; Zhou, Xiao-Jia; Liu, Hong-Li; DU, Li-Li; Toshihisa, Kawai

2010-12-01

The aim of this study was to investigate the effect of vitamine-A deficiency on the induction of specific periodontal pathogenic bacteria A. actinomycetetemcomitans(Aa) immunization. BALB/c mice were fed with vitamine A-depleted diet or control regular diet throughout the whole experiment period. After 2 weeks, immunized formalin-killed Aa to build immunized models, 6 weeks later, sacrificed to determine specific antibody-IgG, IgM and sub-class IgG antibody titers in serum, and concentration of IL-10, IFN-γ, TNF-α and RANKL in T cell supernatant were measured by ELISA and T cell proliferation was measured by cintilography. SPSS 11.5 software package was used for statistical analysis. The levels of whole IgG and IgM antibody which were immunized by Aa significantly elevated, non-immune group was unable to produce any antibody. Compared with Aa immunized+RD group, the level of whole IgG in Aa immunized+VAD group was significantly higher (P<0.05); The levels of IgG2a increased obviously, whereas the levels of IgG1 subtype antibody conspicuous decreased, with a significant difference (P<0.05). Aa immunized group could induce body to produce a strong specific T-cell immune response, but Aa immunized+VAD group had a higher T cell proliferate response compared with Aa immunized+RD group, with a statistically significant difference (P<0.05); The expression of RANKL, IFN-γ and TNF-α supernatant increased, while the expression of IL-10 decreased (P<0.05). The lack of vitamin-A diet can increase the immunized mice's susceptibility to periodontal pathogenic bacteria and trigger or aggravate immune inflammatory response. Adequate vitamin A is an important factor in maintaining body health. Supported by Natural Science Foundation of Liaoning Province (Grant No.20092139) and Science and Technology Program of Shenyang Municipality (Grant No.F10-149-9-32).

Comparison of potential protection conferred by three immunization strategies (protein/protein, DNA/DNA, and DNA/protein) against Brucella infection using Omp2b in BALB/c Mice.

PubMed

Golshani, Maryam; Rafati, Sima; Nejati-Moheimani, Mehdi; Ghasemian, Melina; Bouzari, Saeid

2016-12-25

In the present study, immunogenicity and protective efficacy of the Brucella outer membrane protein 2b (Omp2b) was evaluated in BALB/c mice using Protein/Protein, DNA/DNA and DNA/Protein vaccine strategies. Immunization of mice with three vaccine regimens elicited a strong specific IgG response (higher IgG2a titers over IgG1 titers) and provided Th1-oriented immune response. Vaccination of BALB/c mice with the DNA/Pro regimen induced higher levels of IFN-γ/IL-2 and conferred more protection levels against B. melitenisis and B. abortus challenge than did the protein or DNA alone. In conclusion, Omp2b is able to stimulate specific immune responses and to confer cross protection against B. melitensis and B. abortus infection. Therefore, it could be introduced as a new potential candidate for the development of a subunit vaccine against Brucella infection. Copyright © 2016 Elsevier B.V. All rights reserved.

Serum IgG subclass antibodies to a variety of food antigens in patients with coeliac disease.

PubMed Central

Hvatum, M; Scott, H; Brandtzaeg, P

1992-01-01

Levels of serum IgA, IgG, and IgG subclass antibodies to a variety of dietary antigens were determined by enzyme linked immunosorbent assays in 14 adults with untreated coeliac disease and in 10 disease controls selected because of raised total IgG activities. The untreated coeliacs showed somewhat higher total IgG activity (p approximately 0.05) and significantly raised IgA and IgG1 + IgG3 activities to gliadin but reduced IgG4 activity (p less than 0.02) compared with the controls. High IgA and IgG1 + IgG3 activities were positively correlated (r = 0.67, p less than 0.01), and so were IgG and IgG4 activities (r = 0.64, p less than 0.02). Conversely, a high IgG2 response to gliadin appeared related to a low IgA response (r = 0.55, p less than 0.05). The IgG2 response was most prominent to oat flour antigens, followed by IgG1; and the main response to soy antigens resided in IgG1, followed by IgG2 in both disease groups. There was no difference in antibody activities to oat and soy between the two groups, and raised activity to bovine serum albumin was seldom encountered. The IgA activity to alpha-lactalbumin and ovalbumin tended to be increased in the coeliacs compared with the controls. The IgG4 subclass dominated the IgG response to beta-lactoglobulin and ovalbumin and was often raised to alpha-lactalbumin, especially in the disease controls. The IgG subclass pattern to casein parallelled that to gliadin with dominance of the IgG1- and IgG3-subclass activities, especially in the coeliacs. The phlogistic potential of a response in these two subclasses might be relevant to the pathogenesis of coeliac disease and could contribute to a raised IgA gliadin response by increasing mucosal permeability. IgA activity seemed to be highest against antigens usually involved in IgE mediated food allergy. PMID:1612478

[Preparation of O/W ginseng saponins-based nanoemulsion and its amplified immune response].

PubMed

Cao, Fahao; Ouyang, Wuqing; Wang, Yanping

2010-02-01

To prepare an O/W ginseng saponins-based nanoemulsion and investigate its amplified immune response. The formulation of ginseng saponins-based nanoemulsion was optimized via the range of nanoemulsion zone in phase diagrams and the solubility of ginseng saponins. Its physicochemical properties were investigated, including morphology, particle size distribution, pH, viscosity and stability. Ginseng saponins-based nanoemulsion as adjuvant was co-administrated with a model antigen ovalbumin (OVA) in mice. Two weeks after the boosting, the serum levels of OVA-specific antibody and its isotypes were determined. The optimized ginseng saponins-based nanoemulsion formulation consisted of ginseng saponins, IPM, Cremophor RH 40, glycerol and water (with the weight ratio of 2 : 4 : 17.8 : 17.8 : 58.4), which was a light yellow fluid. The shape of droplets was spherical under transmission electron microscopy with an average diameter of 72.20 nm and a polydispersity index of 0.052. The viscosity and pH value of it were 4.20 s and 6.02, respectively. And it showed good stability. When co-administered with OVA, no obvious side effects were observed in the mice immunized with ginseng saponin-based nanoemulsion. The serum levels of IgG, IgG1 and IgG2a antibody in the group of ginseng saponin-based nanoemulsion immunized mice was significantly increased compared to the groups of OVA and the saline solution of ginseng saponin. Compared with the adjuvant aluminium hydroxide, the serum levels of IgG and IgG1 antibodys in the groups of ginseng saponins-based nanoemulsion had no significant difference, but the level of IgG2a was obviously higher. ginseng saponin-based nanoemulsion could amplify the Th1 and Th2 immune responses, and can be used as the vaccine adjuvant.

Role of immunoglobulin G subclasses in Q fever.

PubMed

Camacho, M T; Outschoorn, I; Tellez, A

1995-12-01

The progression of Q fever to either acute or chronic disease has been attributed both to biological characteristics of the bacteria and to the host immune response. In order to determine whether a specific immunoglobulin G (IgG) subclass distribution could play a diagnostic or prognostic role in Q fever, IgG subclass levels were measured in patients with acute or chronic disease. It was observed that (i) IgG1 and IgG3 levels were elevated in patients with chronic Q fever compared to patients with acute disease or normal controls; (ii) variations over time reflected inverse complementary relationships of subclass levels, such as between IgG1 and IgG3 compared with IgG2 and IgG4, or an inverse relationship between IgG1 and IgG2; (iii) variations in IgG2 and IgG3 total subclass levels during follow-up of patients with chronic Q fever showed a decrease in IgG2 with a concomitant increase in IgG3 two years from disease onset. These findings indicate that measurements of IgG subclasses may be a simple, additional tool useful in the diagnosis of Q fever. This data raises the question of an unusual immunoregulatory mechanism in Q fever that is implicated in the presentation of the clinical disease.

Effects of buffer composition and processing conditions on aggregation of bovine IgG during freeze-drying.

PubMed

Sarciaux, J M; Mansour, S; Hageman, M J; Nail, S L

1999-12-01

The objective of this study was to identify critical formulation and processing variables affecting aggregation of bovine IgG during freeze-drying when no lyoprotective solute is used. Parameters examined were phosphate buffer concentration and counterion (Na versus K phosphate), added salts, cooling rate, IgG concentration, residual moisture level, and presence of a surfactant. No soluble aggregates were detected in any formulation after either freezing/thawing or freeze-drying. No insoluble aggregates were detected in any formulation after freezing, but insoluble aggregate levels were always detectable after freeze-drying. The data are consistent with a mechanism of aggregate formation involving denaturation of IgG at the ice/freeze-concentrate interface which is reversible upon freeze-thawing, but becomes irreversible after freeze-drying and reconstitution. Rapid cooling (by quenching in liquid nitrogen) results in more and larger aggregates than slow cooling on the shelf of the freeze-dryer. This observation is consistent with surface area measurements and environmental electron microscopic data showing a higher surface area of freeze-dried solids after fast cooling. Annealing of rapidly cooled solutions results in significantly less aggregation in reconstituted freeze-dried solids than in nonannealed controls, with a corresponding decrease in specific surface area of the freeze-dried, annealed system. Increasing the concentration of IgG significantly improves the stability of IgG against freeze-drying-induced aggregation, which may be explained by a smaller percentage of the protein residing at the ice/freeze-concentrate interface as IgG concentration is increased. A sodium phosphate buffer system consistently results in more turbid reconstituted solids than a potassium phosphate buffer system at the same concentration, but this effect is not attributable to a pH shift during freezing. Added salts such as NaCl or KCl contribute markedly to insoluble aggregate formation. Both sodium and potassium chloride contribute more to turbidity of the reconstituted solid than either sodium or potassium phosphate buffers at similar ionic strength, with sodium chloride resulting in a substantially higher level of aggregates than potassium chloride. At a given cooling rate, the specific surface area of dried solids is approximately a factor of 2 higher for the formulation containing sodium chloride than the formulation containing potassium chloride. Turbidity is also influenced by the extent of secondary drying, which underscores the importance of minimizing secondary drying of this system. Including a surfactant such as polysorbate 80, either in the formulation or in the water used for reconstitution, decreased, but did not eliminate, insoluble aggregates. There was no correlation between pharmaceutically acceptability of the freeze-dried cake and insoluble aggregate levels in the reconstituted product.

Impact of interleukin-21 in the pathogenesis of primary Sjogren's syndrome: increased serum levels of interleukin-21 and its expression in the labial salivary glands

PubMed Central

2011-01-01

Introduction Interleukin (IL)-21 is a cytokine that controls the functional activity of effector T helper cells and the differentiation of Th17 cells, and promotes B-cell differentiation. To test whether IL-21 participates in the pathogenesis of primary Sjögren's syndrome (SS), serum IL-21 level was measured and IL-21 expression in the labial salivary glands (LSG) was examined. Methods Serum IL-21 levels in 40 primary SS, 40 rheumatoid arthritis (RA), and 38 systemic lupus erythematosus (SLE) patients and 20 healthy controls were measured. Serum IL-21 levels of SS patients were assessed for correlations with laboratory data, including anti-nuclear antibody, anti-Ro/La antibodies, globulin, immunoglobulin (Ig) class, and IgG subclass. LSGs from 16 primary SS and 4 controls with sicca symptoms were evaluated for IL-21 and IL-21 receptor (IL-21R) expression by immunohistochemistry. Confocal microscopy was performed to further characterize the IL-21 positive cells. Results Primary SS patients had significantly higher serum IL-21 levels than controls, and these increments correlated positively with levels of IgG, IgG1. Serum IgG1 levels correlated with anti-Ro antibody titers. Immunohistochemical analyses showed that lymphocytic foci and the periductal area of the LSGs from SS patients expressed high levels of IL-21 and lower levels of IL-21R, whereas the control LSGs showed minimal expression of both antigens. The more the lymphocyte infiltrated, IL-21expression in LSGs showed a tendency to increase. Confocal microscopic analyses revealed that IL-21 expressing infiltrating lymphocytes in the LSGs of SS patients also expressed CXCR5. Conclusions Primary SS is associated with high serum IL-21 levels that correlate positively with serum IgG, especially IgG1, levels. The expression of IL-21 is increased as more lymphocytes infiltrated in LSGs. These observations suggest that IL-21 may play an important role in primary SS pathogenesis. PMID:22030011

Food antigen-induced immune responses in Crohn's disease patients and experimental colitis mice.

PubMed

Kawaguchi, Takaaki; Mori, Maiko; Saito, Keiko; Suga, Yasuyo; Hashimoto, Masaki; Sako, Minako; Yoshimura, Naoki; Uo, Michihide; Danjo, Keiko; Ikenoue, Yuka; Oomura, Kaori; Shinozaki, Junko; Mitsui, Akira; Kajiura, Takayuki; Suzuki, Manabu; Takazoe, Masakazu

2015-04-01

In Crohn's disease (CD), the involvement of food antigens in immune responses remains unclear. The objective of this study was to detect immune responses against food antigens in CD patients and examine the mechanism in a mouse model of colitis. We enrolled 98 CD patients, 50 ulcerative colitis patients, and 52 healthy controls (HCs) to compare the levels of serum immunoglobulin (Ig)Gs against 88 foods. The presence of serum IgGs against foods was also examined in interleukin (IL)-10 knockout (KO) mice in which CD4(+) T cell activation by antigenic food protein was assessed. Mice transferred with IL-10 KO cells received diets with or without food antigens, and the development of colitis was evaluated. The prevalence of IgGs against various foods, especially vegetables, grains, and nuts, was significantly higher in CD patients than in HCs. Similarly, the prevalence of IgGs against food proteins was higher in IL-10 KO mice than in BALB/c mice. Beta-conglycinin, identified as an antigenic food proteins in IL-10 KO mice, induced CD4(+) T cell production of interferon-γ and IL-17 through dendritic cell antigen presentation. Elimination of the food antigens ameliorated the development of colitis in mice without altering the composition of their intestinal microbiota. In CD colitis mice, intestinal inflammation via CD4(+) T cell hyperactivation was induced by food antigens associated with high serum IgG levels and was ameliorated by the elimination of food antigens. This disrupted immunological tolerance to food antigen, which might act as an exacerbating factor, remains to be elucidated in CD patients.

Delivery route determines the presence of immune complexes on umbilical cord erythrocytes.

PubMed

de Lima, Andrés; Franco, Luis C; Sarmiento, Andrés; González, John M

2017-11-01

Umbilical cord blood offers a unique opportunity to study the basal level of immunoglobulin complexes. This study aims to determine the presence of immune complexes and complement deposition on erythrocytes from umbilical cord blood from normal, full-term pregnancies. In vitro pre-formed IgA, IgG, and IgM complexes were used as positive control for flow cytometry detection, and for C3d deposition. Blood samples (34) of umbilical cord blood taken from vaginal and cesarean deliveries were tested for the presence of immunoglobulin complexes. Fourteen samples from vaginal deliveries and 20 samples from cesarean deliveries were assessed. IgG and IgM complexes were detected on erythrocytes, whereas no IgA complexes or complement deposition was observed. Interestingly, the percentage of IgG complexes was higher on erythrocytes from vaginal delivery samples compared to those from cesarean deliveries. No other associations between immune complexes and other maternal or newborn variables were found. IgG and IgM complexes seem to be normally present on umbilical cord erythrocytes. Erythrocytes from vaginal deliveries have a higher percentage of IgG complexes present compared to that from cesarean deliveries. Since no C3d activity was detected, these complexes are non-pathological and should be part of the newborn's initial innate immune response.

Generation of the Fluorescent HMGB1-GFP Fusion Protein in Insect Cells and Evaluation of its Immunogenicity in Two Mice Models.

PubMed

Anvar, Ali; Vahabpour, Rouhollah; Salahshourifar, Iman; Bolhassani, Azam

2017-01-01

High mobility group box 1 (HMGB1) is a highly conserved protein present in the nuclei and cytoplasm of cells which has an important role as a mediator of inflammation in the extracellular environment. HMGB1 was identified as an innate adjuvant that induces immune responses against soluble antigens in vivo. Our goal is the generation of recombinant HMGB1-GFP fusion protein in insect cells for evaluation of immune responses in mouse model. In the current study, we used a baculovirus expression system for insect cells that was based on expression of HMGB1 with target gene (GFP), and purified the recombinant HMGB1- GFP fusion protein. We then demonstrated whether immunogenicity of GFP changes in the presence or absence of recombinant HMGB1 acting as an adjuvant in C57BL/6 and BALB/c mice. Our data showed that HMGB1 had a major influence on antibody immune responses induced by GFP in both animal models. The groups receiving HMGB1-GFP fusion protein showed total IgG and IgG2a responses significantly higher than IgG1 in BALB/c mice. Indeed, a mixed IgG1/IgG2a response was observed with high intensity toward IgG2a. In contrast, C57BL/6 mice immunized by HMGB1-GFP protein elicited the same levels of IgG1 and IgG2a. However, the levels of IgG2a and total IgG against the recombinant GFP (rGFP) in C57BL/6 mice were lower than those in BALB/c mice. We concluded that fusion of HMGB1 with GFP was immunologically more effective than GFP alone. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Factor Xa Mediates Calcium Flux in Endothelial Cells and is Potentiated by Igg From Patients With Lupus and/or Antiphospholipid Syndrome.

PubMed

Artim-Esen, Bahar; Smoktunowicz, Natalia; McDonnell, Thomas; Ripoll, Vera M; Pericleous, Charis; Mackie, Ian; Robinson, Eifion; Isenberg, David; Rahman, Anisur; Ioannou, Yiannis; Chambers, Rachel C; Giles, Ian

2017-09-07

Factor (F) Xa reactive IgG isolated from patients with antiphospholipid syndrome (APS) display higher avidity binding to FXa with greater coagulant effects compared to systemic lupus erythematosus (SLE) non APS IgG. FXa signalling via activation of protease-activated receptors (PAR) leads to increased intracellular calcium (Ca 2+ ). Therefore, we measured alterations in Ca 2+ levels in human umbilical vein endothelial cells (HUVEC) following FXa-mediated PAR activation and investigated whether FXa reactive IgG from patients with APS or SLE/APS- alter these responses. We observed concentration-dependent induction of Ca 2+ release by FXa that was potentiated by APS-IgG and SLE/APS- IgG compared to healthy control subjects' IgG, and FXa alone. APS-IgG and SLE/APS- IgG increased FXa mediated NFκB signalling and this effect was fully-retained in the affinity purified anti-FXa IgG sub-fraction. Antagonism of PAR-1 and PAR-2 reduced FXa-induced Ca 2+ release. Treatment with a specific FXa inhibitor, hydroxychloroquine or fluvastatin significantly reduced FXa-induced and IgG-potentiated Ca 2+ release. In conclusion, PAR-1 and PAR-2 are involved in FXa-mediated intracellular Ca 2+ release in HUVEC and FXa reactive IgG from patients with APS and/or SLE potentiate this effect. Further work is required to explore the potential use of IgG FXa reactivity as a novel biomarker to stratify treatment with FXa inhibitors in these patients.

Diphtheria toxoid loaded poly-(epsilon-caprolactone) nanoparticles as mucosal vaccine delivery systems.

PubMed

Singh, Jasvinder; Pandit, Sreenivas; Bramwell, Vincent W; Alpar, H Oya

2006-02-01

Poly-(epsilon-caprolactone) (PCL), a poly(lactide-co-glycolide) (PLGA)-PCL blend and co-polymer nanoparticles encapsulating diphtheria toxoid (DT) were investigated for their potential as a mucosal vaccine delivery system. The nanoparticles, prepared using a water-in-oil-in-water (w/o/w) double emulsion solvent evaporation method, demonstrated release profiles which were dependent on the properties of the polymers. An in vitro experiment using Caco-2 cells showed significantly higher uptake of PCL nanoparticles in comparison to polymeric PLGA, the PLGA-PCL blend and co-polymer nanoparticles. The highest uptake mediated by the most hydrophobic nanoparticles using Caco-2 cells was mirrored in the in vivo studies following nasal administration. PCL nanoparticles induced DT serum specific IgG antibody responses significantly higher than PLGA. A significant positive correlation between hydrophobicity of the nanoparticles and the immune response was observed following intramuscular administration. The positive correlation between hydrophobicity of the nanoparticles and serum DT specific IgG antibody response was also observed after intranasal administration of the nanoparticles. The cytokine assays showed that the serum IgG antibody response induced is different according to the route of administration, indicated by the differential levels of IL-6 and IFN-gamma. The nanoparticles eliciting the highest IgG antibody response did not necessarily elicit the highest levels of the cytokines IL-6 and IFN-gamma.

A low redox potential affects monoclonal antibody assembly and glycosylation in cell culture.

PubMed

Dionne, Benjamin; Mishra, Neha; Butler, Michael

2017-03-20

Glycosylation and intracellular assembly of monoclonal antibodies (MAbs) is important for glycan profile consistency. To better understand how these factors may be influenced by a lower redox potential, an IgG1-producing NS0 cell line was grown in the presence of varying concentrations of dithiothreitol (DTT). Cultures were monitored for growth and culture redox potential (CRP) with glycan heterogeneity determined using a HILIC-HPLC method. Macroheterogeneity was unchanged in all conditions whereas the Galactosylation Index (GI) decreased by as much as 50% in cultures with lower CRP or higher dithiothreitol levels. This shift in GI is reflected in more agalactosylated and asialylated species being produced. The MAb assembly pathway was determined using radioactive isotope 35 S incorporated into nascent IgG1 molecules. The assembly pathway for this IgG1 was shown to progress via HC→HC 2 →HC 2 LC→HC 2 LC 2 in all conditions tested and autoradiographs highlighted that the ratio of heavy chain dimer to heavy chain monomer increased over time with increasing DTT concentrations. This increase and correspondingly lower GI values may be due to disruption of the disulfide bonds at higher levels of assembly. A change in the assembly pathway may alter the final IgG glycan pattern and lead to control mechanisms that influence glycan profiles of MAbs. Copyright © 2017. Published by Elsevier B.V.

Enhanced protection against Clonorchis sinensis induced by co-infection with Trichinella spiralis in rats.

PubMed

Chu, K-B; Kim, S-S; Lee, S-H; Lee, H-S; Joo, K-H; Lee, J-H; Lee, Y-S; Zheng, S; Quan, F-S

2014-10-01

Although co-infection with multiple parasites is a frequent occurrence, changes in the humoral immune response against a pre-existing parasite induced as a result of a subsequent parasitic infection remain undetermined. Here, we utilized enzyme-linked immunosorbent assay (ELISA) to investigate antibody responses, cytokine production and enhanced resistance in Clonorchis sinensis-infected rats (Sprague-Dawley) upon Trichinella spiralis infection. Higher levels of C. sinensis-specific IgG and IgA were elicited upon T. spiralis infection, and these levels remained higher than in rats infected with C. sinensis alone. Upon subsequent infection with T. spiralis, IgG antibodies against C. sinensis appeared to be rapidly boosted at day 3, and IgA antibodies were boosted at day 7. Challenge infection of C. sinensis-infected rats with T. spiralis induced substantial mucosal IgG and IgA responses in the liver and intestine and increases in antibody-secreting plasma cells in the spleen and bone marrow. Subsequent infection also appeared to confer effective control of liver C. sinensis loads, resulting in enhanced resistance. Memory B cells generated in response to C. sinensis infection were rapidly amplified into antibody-secreting cells upon T. spiralis infection. These results indicate that enhanced C. sinensis clearance induced by co-infection is associated with systemic and mucosal IgG and IgA responses. © 2014 John Wiley & Sons Ltd.

Toxoplasma gondii Infection and Headache: A Matched Case-Control Study in a Public Hospital in Durango City, Mexico

PubMed Central

Alvarado-Esquivel, Cosme; Rico-Almochantaf, Yazmin del Rosario; Sanchez-Anguiano, Luis Francisco; Quinones-Canales, Gerardo; Hernandez-Tinoco, Jesus; Torres-Gonzalez, Jorge; Gonzalez-Silva, Maria Felix; Ramirez-Valles, Eda Guadalupe

2018-01-01

Background Toxoplasma gondii (T. gondii) can disseminate to brain in infected hosts. Little is known about the magnitude of the association between this infection and headache. Therefore, we sought to determine the association of T. gondii seropositivity and headache in patients attending neurological consultations in a public hospital in Durango City, Mexico. Methods Through an age- and gender-matched case-control study, 105 patients suffering from headache and 105 subjects without headache were examined for anti-T. gondii IgG and IgM antibodies using commercially available enzyme-linked immunoassays. Seropositive cases were analyzed for detection of T. gondii DNA by polymerase chain reaction. Results Anti-T. gondii IgG antibodies were found in five (4.8%) of the 105 cases and in seven (6.7%) of the 105 controls (odds ratio (OR) = 0.70; 95% confidence interval (CI): 0.21 - 2.28; P = 0.76). The frequency of high (> 150 IU/mL) levels of anti-T. gondii IgG antibodies among anti-T. gondii IgG positive individuals was significantly (P = 0.01) higher in cases (5/5) than in controls (1/7). Anti-T. gondii IgM antibodies were found in one (20.0%) of the five IgG seropositive cases, and in three (42.9%) of the seven IgG seropositive controls (P = 0.60). T. gondii DNA was not detected in any of the five anti-T. gondii IgG positive cases. No association between T. gondii infection and specific headache types was found. Conclusions This is the first matched case-control study on the association between T. gondii infection and headache. Results suggest that high anti-T. gondii IgG antibody levels, but not T. gondii seropositivity, were associated with headache in the population studied. PMID:29238431

Toxoplasma gondii Infection and Headache: A Matched Case-Control Study in a Public Hospital in Durango City, Mexico.

PubMed

Alvarado-Esquivel, Cosme; Rico-Almochantaf, Yazmin Del Rosario; Sanchez-Anguiano, Luis Francisco; Quinones-Canales, Gerardo; Hernandez-Tinoco, Jesus; Torres-Gonzalez, Jorge; Gonzalez-Silva, Maria Felix; Ramirez-Valles, Eda Guadalupe

2018-01-01

Toxoplasma gondii ( T. gondii ) can disseminate to brain in infected hosts. Little is known about the magnitude of the association between this infection and headache. Therefore, we sought to determine the association of T. gondii seropositivity and headache in patients attending neurological consultations in a public hospital in Durango City, Mexico. Through an age- and gender-matched case-control study, 105 patients suffering from headache and 105 subjects without headache were examined for anti- T. gondii IgG and IgM antibodies using commercially available enzyme-linked immunoassays. Seropositive cases were analyzed for detection of T. gondii DNA by polymerase chain reaction. Anti- T. gondii IgG antibodies were found in five (4.8%) of the 105 cases and in seven (6.7%) of the 105 controls (odds ratio (OR) = 0.70; 95% confidence interval (CI): 0.21 - 2.28; P = 0.76). The frequency of high (> 150 IU/mL) levels of anti- T. gondii IgG antibodies among anti- T. gondii IgG positive individuals was significantly (P = 0.01) higher in cases (5/5) than in controls (1/7). Anti- T. gondii IgM antibodies were found in one (20.0%) of the five IgG seropositive cases, and in three (42.9%) of the seven IgG seropositive controls (P = 0.60). T. gondii DNA was not detected in any of the five anti- T. gondii IgG positive cases. No association between T. gondii infection and specific headache types was found. This is the first matched case-control study on the association between T. gondii infection and headache. Results suggest that high anti- T. gondii IgG antibody levels, but not T. gondii seropositivity, were associated with headache in the population studied.

[Serum levels of antibodies for IgG, IgA, and IgM against the fungi antigen in psoriasis vulgaris].

PubMed

Liang, Yun-sheng; Wen, Hai-quan; Xiao, Rong

2003-12-01

To detect the serum levels of antibodies against Malassezia further and Candida albicans in patients with psoriasis vulgaris (PV), and to investigate the relationship between Malassezia furfur or Candida albicans and pathogenesis of PV. The serum levels of antibodies for IgG, IgA, and IgM against the whole cell antigen Wag and soluble antigen (Sag) of Malassezia fufur and Candida albicans in 40 PV patients and 20 healthy controls were detected by indirect-ELISA, RESULTS: The serum levels of IgG against Wag of Malassezia furfur and Candida albicans were significantly higher in PV patients than those in the healthy controls (P < 0.01, P < 0.05, respectively), The serum levels of IgM against Sag of Malassezia furfur and Candida albican, IgA against Sag of Candida albicans were significantly lower in PV patients than those in the healthy controls (P < 0.05). There are some humoral immunity abnormalties in PV patients. Malassezia furfur and Candida albicans may be related to the pathogenesis of PV.

Anti-food and anti-microbial IgG subclass antibodies in inflammatory bowel disease.

PubMed

Jansen, Anke; Mandić, Ana D; Bennek, Eveline; Frehn, Lisa; Verdier, Julien; Tebrügge, Irene; Lutz, Holger; Streetz, Konrad; Trautwein, Christian; Sellge, Gernot

2016-12-01

Inflammatory bowel disease (IBD), particularly Crohn's disease (CD), is associated with increased microbial-specific IgG and IgA antibodies, whereas alterations of anti-food antibodies are still disputed. The knowledge about IgG subclass antibodies in IBD is limited. In this study we analysed IgG subclass antibodies specific for nutritional and commensal antigens in IBD patients and controls. Serum IgG1, IgG2, IgG3 and IgG4 specific for wheat and milk extracts, purified ovalbumin, Escherichia coli and Bacteroides fragilis lysates and mannan from Saccharomyces cerevisiae were analysed by ELISA in patients with CD (n = 56), ulcerative colitis (UC; n = 29), acute gastroenteritis/colitis (n = 12) as well as non-inflammatory controls (n = 62). Anti-Saccharomyces cerevisiae antibodies (ASCA) of all IgG subclasses and anti-B. fragilis IgG1 levels were increased in CD patients compared to UC patients and controls. The discriminant validity of ASCA IgG2 and IgG4 was comparable with that of ASCA pan-IgG and IgA, whereas it was inferior for ASCA IgG1/IgG3 and anti-B. fragilis IgG1. Complicated CD defined by the presence of perianal, stricturing or penetrating disease phenotypes was associated with increased ASCA IgG1/IgG3/IgG4, anti-B. fragilis IgG1 and anti-E. coli IgG1 levels. Anti-food IgG subclass levels were not different between IBD patients and controls and did not correlate with food intolerance. In contrast to anti-microbial Abs, food-specific IgG responses were predominately of the IgG4 isotype and all food-specific IgG subclass levels correlated negatively with age. Our study supports the notion that the adaptive immune recognition of food and commensal antigens are differentially regulated.

Coexistence of anti-β2-glycoprotein I domain I and anti-phosphatidylserine/prothrombin antibodies suggests strong thrombotic risk.

PubMed

Lee, Jee-Soo; Gu, JaYoon; Park, Hee Sue; Yoo, Hyun Ju; Kim, Hyun Kyung

2017-05-01

Highly specific assays for measuring antiphospholipid antibodies (aPLs) are required for accurate assessment of thrombotic risk. aPLs against β2-glycoprotein I domain I (anti-β2GPIdI) and against prothrombin complexed with phosphatidylserine (anti-PS/PT) have been recently identified as being associated with a hypercoagulable state. This study evaluated the synergism between anti-β2GPIdI and anti-PS/PT for predicting thrombotic events. A total of 180 patients with clinical suspicion of hypercoagulability were evaluated. The plasma levels of lupus anticoagulant (LA) and antibodies against anticardiolipin (anti-CL) (IgG and IgM), β2GPI (IgG and IgM), PS/PT (IgG and IgM), and β2GPI dI (IgG) were measured. IgG anti-β2GPIdI and LA were highly associated with thrombosis. Mean values and positivity rates of IgG anti-β2GPI dI and IgG anti-PS/PT were significantly higher in the triple-positive group (LA+, IgG anti-CL+, IgG anti-β2GPI+) than in the other groups. Interestingly, the thrombotic risk [odds ratio (OR) 24.400, 95% confidence interval (CI) 1.976-63.273, p<0.001] of the newly defined triple positive group (LA+, IgG anti-CL+, IgG anti-β2GPIdI+; OR 11.182, 95% CI 1.976-63.273, p=0.006) was more than twice that of the triple-positive group (LA+, IgG anti-CL+, IgG anti-β2GPI+). Double positivity for IgG anti-PS/PT and IgG anti-β2GPI also indicated significant thrombotic risk (OR 7.467, 95% CI 2.350-23.729, p=0.001). Furthermore, the thrombotic risk associated with double positivity for IgG anti-PS/PT and IgG anti-β2GPIdI was markedly elevated (OR 33.654, 95% CI 6.322-179.141, p<0.001). Our data suggest that simultaneous measurement of IgG anti-β2GPIdI and IgG anti-PS/PT may improve clinical decision-making for aPL-positive patients.

Monitoring of early humoral immunity to identify lung recipients at risk for development of serious infections: A multicenter prospective study.

PubMed

Sarmiento, Elizabeth; Cifrian, Jose; Calahorra, Leticia; Bravo, Carles; Lopez, Sonia; Laporta, Rosalia; Ussetti, Piedad; Sole, Amparo; Morales, Carmen; de Pablos, Alicia; Jaramillo, Maria; Ezzahouri, Ikram; García, Sandra; Navarro, Joaquin; Lopez-Hoyos, Marcos; Carbone, Javier

2018-04-06

Infection is still a leading cause of death during the first year after lung transplantation. We performed a multicenter study among teaching hospitals to assess monitoring of early humoral immunity as a means of identifying lung recipients at risk of serious infections. We prospectively analyzed 82 adult lung recipients at 5 centers in Spain. Data were collected before transplantation and at 7 and 30 days after transplantation. Biomarkers included IgG, IgM, IgA, complement factors C3 and C4, titers of antibodies to pneumococcal polysaccharide antigens (IgG, IgA, IgM) and antibodies to cytomegalovirus (IgG), and serum B-cell activating factor (BAFF) levels. The clinical follow-up period lasted 6 months. Clinical outcomes were bacterial infections requiring intravenous anti-microbial agents, cytomegalovirus (CMV) disease, and fungal infections requiring therapy. We found that 33 patients (40.2%) developed at least 1 serious bacterial infection, 8 patients (9.8%) had CMV disease, and 10 patients (12.2%) had fungal infections. Lower IgM antibody levels against pneumococcal polysaccharide antigens at Day 7 (defined as <5 mg/dl) were a risk factor for serious bacterial infection (adjusted odds ratio [OR] 3.96; 95% confidence interval [CI] 1.39 to 11.26; p = 0.0099). At Day 7 after transplantation, IgG hypogammaglobulinemia (defined as IgG <600 mg/dl) was associated with a higher risk of CMV disease (after adjustment for CMV mismatch: OR 8.15; 95% CI 1.27 to 52.55; p = 0.028) and fungal infection (adjusted OR 8.03, 95% CI 1.51 to 42.72; p = 0.015). Higher BAFF levels before transplantation were associated with a higher rate of development of serious bacterial infection and acute cellular rejection. Early monitoring of specific humoral immunity parameters proved useful for the identification of lung recipients who are at risk of serious infections. Copyright © 2018 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Immune mediators associated to male infertility in a mouse model of DNA immunization with the sperm protease proacrosin.

PubMed

Russi, Romina; García, María Inés; Vignatti, Paulina; Veiga, María Florencia; Vazquez-Levin, Mónica Hebe; Veaute, Carolina

2016-11-01

The immune response has relevant physiological functions both in the male and female reproductive system, and must be tightly controlled to achieve a successful pregnancy. Several immune factors have been related to infertility, among them humoral and cellular immune responses triggered by sperm antigens. The present study was aimed at evaluating the immune profile induced by DNA immunization against the sperm protease proacrosin in CF1 male mice and its effect upon fertility. Immunized animals exhibited higher anti-proacrosin antibodies levels than controls (indirect ELISA), both in serum (p<0.01) and in seminal vesicle fluid (SVF; p<0.05). IgG2a levels were higher than IgG1 in serum (p<0.01) and similar in SVF. IL-10 and TGF-β1 mRNA levels were lower in testis (p<0.05), whereas TNF-α and IFN-γ transcript levels were increased in SV tissue (p<0.05). Immunized mice showed a trend toward higher IFN-γ concentration in serum and SVF than controls. Male fertility rate was diminished in immunized mice (p<0.01) and inversely correlated with serum and SVF anti-proacrosin IgG levels (p<0.001). Immunized animals also had fewer pups born than controls (p<0.01). To our knowledge, this is the first report on DNA immunization done in CF1 mice. Injection of proacrosin DNA induces an immune response in the male reproductive tract characterized by high levels of specific antibodies and cytokine changes. These factors may alter the crucial balance of the genital tract microenvironment required for adequate fertilization and pregnancy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Multiplexing detection of IgG against Plasmodium falciparum pregnancy-specific antigens

PubMed Central

Fonseca, Ana Maria; Quinto, Llorenç; Jiménez, Alfons; González, Raquel; Bardají, Azucena; Maculuve, Sonia; Dobaño, Carlota; Rupérez, Maria; Vala, Anifa; Aponte, John J.; Sevene, Esperanza; Macete, Eusebio; Menéndez, Clara

2017-01-01

Background Pregnant women exposed to Plasmodium falciparum generate antibodies against VAR2CSA, the parasite protein that mediates adhesion of infected erythrocytes to the placenta. There is a need of high-throughput tools to determine the fine specificity of these antibodies that can be used to identify immune correlates of protection and exposure. Here we aimed at developing a multiplex-immunoassay to detect antibodies against VAR2CSA antigens. Methods and findings We constructed two multiplex-bead arrays, one composed of 3 VAR2CSA recombinant-domains (DBL3X, DBL5Ɛ and DBL6Ɛ) and another composed of 46 new peptides covering VAR2CSA conserved and semi-conserved regions. IgG reactivity was similar in multiplexed and singleplexed determinations (Pearson correlation, protein array: R2 = 0.99 and peptide array: R2 = 0.87). IgG recognition of 25 out of 46 peptides and all recombinant-domains was higher in pregnant Mozambican women (n = 106) than in Mozambican men (n = 102) and Spanish individuals (n = 101; p<0.05). Agreement of IgG levels detected in cryopreserved plasma and in elutions from dried blood spots was good after exclusion of inappropriate filter papers. Under heterogeneous levels of exposure to malaria, similar seropositivity cutoffs were obtained using finite mixture models applied to antibodies measured on pregnant Mozambican women and average of antibodies measured on pregnant Spanish women never exposed to malaria. The application of the multiplex-bead array developed here, allowed the assessment of higher IgG levels and seroprevalences against VAR2CSA-derived antigens in women pregnant during 2003–2005 than during 2010–2012, in accordance with the levels of malaria transmission reported for these years in Mozambique. Conclusions The multiplex bead-based immunoassay to detect antibodies against selected 25 VAR2CSA new-peptides and recombinant-domains was successfully implemented. Analysis of field samples showed that responses were specific among pregnant women and dependent on the level of exposure to malaria. This platform provides a high-throughput approach to investigating correlates of protection and identifying serological markers of exposure for malaria in pregnancy. PMID:28715465

Organochlorine and trace element contamination in wintering and migrating diving ducks in the southern Great Lakes, USA, since the zebra mussel invasion

USGS Publications Warehouse

Custer, Christine M.; Custer, T.W.

2000-01-01

Because of the potential for increased trophic transfer of contaminants by zebra mussels (Dreissena sp.) to higher trophic levels, we collected four species of waterfowl (n = 65 ducks) from four locations in Lake Erie, Lake St. Clair, and Lake Michigan, USA, between 1991 and 1993 for organochlorine contaminant and trace element analyses. Geometric mean concentrations of total polychlorinated biphenyls (PCBs) and p,pa??-dichlorodiphenyldichloroethylene (DDE) were 1.35 and 0.15 I?g/g wet weight in lesser scaup (Aythya affinis) carcasses and were below known effect levels. Total PCBs in 80% of carcasses, however, were above the U.S. Food and Drug Administration's threshold of 3.0 I?g/g lipid weight for consumption of poultry. With the exception of selenium, trace elements were also at background or no-effect levels. Selenium concentrations in livers of 95% of lesser scaup, 90% of bufflehead (Bucephala albeola), and 72% of common goldeneye (Bucephala clangula) were in the elevated (>10 I?g/g dry wt) or potentially harmful range (>33 I?g/g dry wt). The effects of these high selenium concentrations are unknown but should be investigated further based on reproductive effects observed in field and laboratory studies of dabbling ducks and because lesser scaup populations are declining. Concentrations of total PCBs in dreissenid mussels in western Lake Erie were 10 times higher than in the upper Mississippi River but were similar to concentrations in other industrialized rivers in Europe and the United States. Metal concentrations were similar to other industrialized sites where zebra mussels have been sampled.

IgG subclass alterations in adult asthma.

PubMed

Outschoorn, I M; Natta, C L

1992-01-01

Immunoglobulin levels were measured in serum samples of 12 black adult non-smoking asthmatic patients, 11 females and 1 male, and compared with 15 age-, sex-matched normal controls. Their total IgG, IgA and IgM levels were within the normal range. However, on quantitation of subclasses, IgG1 levels were significantly above normal, while IgG2 and IgG3 levels were significantly lower than those of controls. No significant differences were found between the two groups when IgG4 levels were compared. These studies as well as those of others suggest that immunoglobulin administration, particularly of individual subclasses, might prove to be a beneficial addition in the management of this condition.

Fibre Optic Sensors Using Adiabatically Tapered Single Mode Fibres

DTIC Science & Technology

1994-02-01

strum in 980 ~i! of buffer. Tne f’uorescent levels seen in this immunoassay are also higher, than what can be predicted using the p + S p estimates ...labelled IgG versus amount of IgG present in various dilutions (serial) of sera sample. .............. 107 Figure I-I Sensing arrangements used in the...case for sensor work in cations is the detection of pH change, sometimes for industrial applications. Further, since pH can be used to diagnose changes

IgG4-related Pleuritis with Elevated Adenosine Deaminase in Pleural Effusion: A Case Report.

PubMed

Nagayasu, Atsushi; Kubo, Satoshi; Nakano, Kazuhisa; Nakayamada, Shingo; Iwata, Shigeru; Miyagawa, Ippei; Fukuyo, Shunsuke; Saito, Kazuyoshi; Tanaka, Yoshiya

2018-03-09

An 81-year-old man was admitted with bilateral pleural effusion. A clinical examination showed lymphocytic pleura effusion and elevated serum IgG4 levels, so that IgG4-related disease was suggested, whereas tuberculous pleurisy was suspected because of high adenosine deaminase (ADA) levels in the pleural effusion. A surgical pleural biopsy revealed that there were large numbers of IgG4-positive cells and IgG4/IgG positive cell ratio exceeded 40% in several sites. Accordingly, we diagnosed IgG4-related pleuritis and treated with the patient with glucocorticoid therapy. The ADA levels in pleural effusion can increase in IgG4-related pleuritis, and it is therefore important to perform a pleural biopsy.

Immunoglobulin class switching to IgG4 in Warthin tumor and analysis of serum IgG4 levels and IgG4-positive plasma cells in the tumor.

PubMed

Aga, Mitsuharu; Kondo, Satoru; Yamada, Kazunori; Wakisaka, Naohiro; Yagi-Nakanishi, Sayaka; Tsuji, Akira; Endo, Kazuhira; Murono, Shigeyuki; Ito, Makoto; Muramatsu, Masamichi; Kawano, Mitsuhiro; Yoshizaki, Tomokazu

2014-04-01

We previously reported a case of immunoglobulin (Ig)G4-related immune inflammation in Warthin tumor. Increased serum IgG4 levels and tissue infiltration of IgG4-positive plasma cells are characteristics of IgG4-related disease (IgG4-RD), a newly emerging clinicopathological entity. However, the relationship between IgG4-RD and Warthin tumor remains to be elucidated. We aimed to investigate the involvement of systemic and local IgG4 production and class-switch recombination in Warthin tumor. We examined serum IgG4 levels and also analyzed the involvement of IgG4-positive plasma cells in Warthin tumors (18 cases) compared with those of pleomorphic adenomas (19 cases) as controls. Furthermore, in specimens of Warthin tumors (3 cases), pleomorphic adenomas (2 cases), and IgG4-RDs (2 cases), we examined messenger RNA expression of activation-induced cytidine deaminase, IgG4 germline transcripts and productive IgG4 by reverse transcription polymerase chain reaction. Serum IgG4 levels were increased in 5 of 18 Warthin tumors and not in any of the 19 pleomorphic adenomas. Infiltration of IgG4-positive plasma cells was detected in 4 Warthin tumors and none in the pleomorphic adenomas. Moreover, activation-induced cytidine deaminase, IgG4 germline transcripts, and productive IgG4 messenger RNA were found to be expressed in 2 of 3 Warthin tumors as well as IgG4-RDs by reverse transcription polymerase chain reaction, but not in pleomorphic adenomas. In conclusion, immunoglobulin class switching to IgG4 may be involved in the pathogenesis of Warthin tumor, and it is possible that certain inflammatory background with an immune reaction is involved in the pathogenesis of Warthin tumor. © 2013.

Measurement of the IgG2 response to Pneumococcal capsular polysaccharides may identify an antibody deficiency in individuals referred for immunological investigation.

PubMed

Parker, Antony; Irure Ventura, Juan; Sims, Dawn; Echeverría de Carlos, Ainara; Gómez de la Torre, Ricardo; Tricas Aizpún, Lourdes; Ocejo-Vinyals, J Gonzalo; López-Hoyos, Marcos; Wallis, Gregg; Harding, Stephen

2017-01-01

IgG2 is the most efficient subclass for providing protection against pneumococcal pathogens. We hypothesised that some individuals may be unable to mount an effective pneumococcal capsular polysaccharide (PCP) IgG2 response despite having a normal PCP IgG concentration (PCP IgG2 deficient). The median pre-vaccination PCP IgG2 concentration was significantly lower in individuals referred for immunological investigation compared to healthy controls (2.8 mg/L range, 95% CI 1.1-88 vs. 29.5mg/L, 95% CI 13.5-90, p = 0.0002). PCP IgG:IgG2 ratios were significantly higher for the referral population than for healthy controls suggesting the increased production of PCP specific subclasses other than IgG2. The percentage of individuals with PCP IgG2 deficiency was significantly higher in referral groups compared to controls (31% vs. 5%; p = 0.0009) and in an individual with PCP IgG2 deficiency, the balance of PCP specific IgG subclass antibodies post vaccination changed from IgG2>IgG1>IgG3>IgG4 to IgG1>IgG3>IgG2>IgG4. The median PCP IgG2 concentration in those with PCP IgG2 deficiency was significantly lower in the referral groups compared to controls (7.8 mg/L, 95% CI 1.1-12 vs. 12.7 mg/L, 95% CI 11.8-13.1; p = 0.006). The data suggests a defect in the production PCP IgG2 may be present in individuals with normal PCP IgG referred for immunological investigation.

Performance of LBSap Vaccine after Intradermal Challenge with L. infantum and Saliva of Lu. longipalpis: Immunogenicity and Parasitological Evaluation

PubMed Central

Roatt, Bruno Mendes; Aguiar-Soares, Rodrigo Dian de Oliveira; Vitoriano-Souza, Juliana; Coura-Vital, Wendel; Braga, Samuel Leôncio; Corrêa-Oliveira, Rodrigo; Martins-Filho, Olindo Assis; Teixeira-Carvalho, Andréa; de Lana, Marta; Gontijo, Nelder Figueiredo; Marques, Marcos José; Giunchetti, Rodolfo Cordeiro; Reis, Alexandre Barbosa

2012-01-01

In the last decade, the search for new vaccines against canine visceral leishmaniasis has intensified. However, the pattern related to immune protection during long periods after experimental infection in vaccine trials is still not fully understood. Herein, we investigated the immunogenicity and parasitological levels after intradermal challenge with Leishmania infantum plus salivary gland extract in dogs immunized with a vaccine composed of L. braziliensis antigens plus saponin as an adjuvant (LBSap vaccine). The LBSap vaccine elicited higher levels of total anti-Leishmania IgG as well as both IgG1 and IgG2. Furthermore, dogs vaccinated had increased levels of lymphocytes, particularly circulating B cells (CD21+) and both CD4+ and CD8+ T lymphocytes. LBSap also elicited an intense in vitro cell proliferation associated with higher levels of CD4+ T lymphocytes specific for vaccine soluble antigen and soluble lysate of L. infantum antigen even 885 days after experimental challenge. Furthermore, LBSap vaccinated dogs presented high IFN-γ and low IL-10 and TGF-β1 expression in spleen with significant reduction of parasite load in this tissue. Overall, our results validate the potential of LBSap vaccine to protect against L. infantum experimental infection and strongly support further evaluation of efficiency of LBSap against CVL in natural infection conditions. PMID:23189161

The isotype repertoire of antibodies against novel UH-RA peptides in rheumatoid arthritis.

PubMed

De Winter, Liesbeth M; Geusens, Piet; Lenaerts, Jan; Vanhoof, Johan; Stinissen, Piet; Somers, Veerle

2016-06-07

Recently, autoantibodies against novel UH-RA peptides (UH-RA.1 and UH-RA.21) were identified as candidate biomarkers for patients with rheumatoid arthritis (RA) who are seronegative for the current diagnostic markers rheumatoid factor and anticitrullinated protein antibodies. Previously, screening for anti-UH-RA autoantibodies was based on measuring the immunoglobulin (Ig) G response. We aimed to investigate whether measurement of other isotypes could improve the performance of diagnostic testing. In addition, assigning the isotype profile might provide valuable information on effector functions of the antibodies. The isotype profile of antibodies against UH-RA.1 and UH-RA.21 was studied. The IgG, IgM, and IgA classes, together with the 4 different IgG subclasses, were determined in 285 patients with RA, 88 rheumatic control subjects, and 90 healthy control subjects. Anti-UH-RA.1 antibodies were primarily of the IgM isotype and twice as prevalent as IgG (IgG3-dominated) and IgA. RA sensitivity when testing for anti-UH-RA.1 IgM was shown to be higher than when testing for the IgG isotype: 18 % versus 9 % sensitivity when RA specificity was set to 90 %. Within antibodies against UH-RA.21, IgG and IgA were more common than IgM. Different anti-UH-RA.21 IgG subclasses were found, with the highest prevalence found for IgG2. Combined testing for IgG and IgA slightly increased RA sensitivity of UH-RA.21-specific antibody testing to 27 % compared with solely testing for IgG (23 %). Notably, a higher number of anti-UH-RA.21 antibody isotypes was related to increased levels of erythrocyte sedimentation rate. Finally, for both antibody responses, the full antibody isotype use was demonstrated in early and seronegative disease. The isotype distribution of anti-UH-RA.1 and anti-UH-RA.21 antibodies was successfully outlined, and, for antibodies against UH-RA.1, we found that isotype-specific testing might have implications for diagnostic testing. The exact mechanisms by which the different antibody isotypes act still have to be unraveled.

Impact of age of first exposure to Plasmodium falciparum on antibody responses to malaria in children: a randomized, controlled trial in Mozambique

PubMed Central

2014-01-01

Background The impact of the age of first Plasmodium falciparum infection on the rate of acquisition of immunity to malaria and on the immune correlates of protection has proven difficult to elucidate. A randomized, double-blind, placebo-controlled trial using monthly chemoprophylaxis with sulphadoxine-pyrimethamine plus artesunate was conducted to modify the age of first P. falciparum erythrocytic exposure in infancy and assess antibodies and malaria risk over two years. Methods Participants (n = 349) were enrolled at birth to one of three groups: late exposure, early exposure and control group, and were followed up for malaria morbidity and immunological analyses at birth, 2.5, 5.5, 10.5, 15 and 24 months of age. Total IgG, IgG subclasses and IgM responses to MSP-119, AMA-1, and EBA-175 were measured by ELISA, and IgG against variant antigens on the surface of infected erythrocytes by flow cytometry. Factors affecting antibody responses in relation to chemoprophylaxis and malaria incidence were evaluated. Results Generally, antibody responses did not vary significantly between exposure groups except for levels of IgM to EBA-175, and seropositivity of IgG1 and IgG3 to MSP-119. Previous and current malaria infections were strongly associated with increased IgG against MSP-119, EBA-175 and AMA-1 (p < 0.0001). After adjusting for exposure, only higher levels of anti-EBA-175 IgG were significantly associated with reduced clinical malaria incidence (IRR 0.67, p = 0.0178). Conclusions Overall, the age of first P. falciparum infection did not influence the magnitude and breadth of IgG responses, but previous exposure was critical for antibody acquisition. IgG responses to EBA-175 were the strongest correlate of protection against clinical malaria. Trial registration ClinicalTrials.gov: NCT00231452. PMID:24674654

Hashimoto's thyroiditis with elevated serum IgG4 concentrations is not equivalent to IgG4 Hashimoto's thyroiditis.

PubMed

Yu, Yang; Yu, Nan; Lu, Guizhi; Li, Ting; Zhang, Yang; Zhang, Jing; Gao, Ying; Gao, Yanming; Guo, Xiaohui

2018-06-01

Hashimoto's thyroiditis (HT) with serum IgG4 concentrations greater than 135 mg/dL can be diagnosed as elevated serum IgG4 HT. HT can also be classified into IgG4 HT and non-IgG4 HT based on an immunohistochemistry analysis of IgG4. The aim of our study was to determine the relationship between elevated serum IgG4 HT and IgG4 HT. Both thyroid tissues and serum samples stored before pathological examination from 93 patients with HT were collected. The serum levels of IgG, IgG4, TgAb IgG, TgAb IgG4, TPOAb IgG and TPOAb IgG4 were measured by ELISAs. The expression levels of IgG4, IgG and TGF-β1 in thyroid tissues were detected by immunohistochemistry. Patients with HT were divided into two groups: elevated serum IgG4 HT (n = 12) and nonelevated serum IgG4 HT (n = 81). Hypothyroidism was found in 5 of 12 cases (41.7%) in the elevated serum IgG4 HT group and 10 of 81 cases (12.3%) in the nonelevated serum IgG4 HT group (P = .023). Serologically, there were no significant differences in the levels of TgAb IgG, TPOAb IgG, TgAb IgG4 and TPOAb IgG4 between the two groups, and the expression of TGF-β1 in thyroid tissues was not significantly different between the groups. Most importantly, the frequency of patients who satisfied the criteria for IgG4 HT diagnosis was comparable (25% vs 20.9%, P = .756). The measurement of serum IgG4 allows the identification of patients with HT closely associated with hypothyroidism. However, our study demonstrated that elevated serum IgG4 HT is not equivalent to IgG4 HT. © 2018 John Wiley & Sons Ltd.

A lentiviral vaccine expressing KMP11-HASPB fusion protein increases immune response to Leishmania major in BALB/C.

PubMed

Mortazavidehkordi, Nahid; Fallah, Ali; Abdollahi, Abbas; Kia, Vahid; Khanahmad, Hossein; Najafabadi, Zahra Ghayour; Hashemi, Nooshin; Estiri, Bahareh; Roudbari, Zahra; Najafi, Ali; Farjadfar, Akbar; Hejazi, Seyed Hossein

2018-05-29

Hydrophilic acylated surface protein B (HASPB) is an immunogenic Leishmania-specific protein that antibodies are produced against it in the sera of Leishmania-infected individuals. Kinetoplastid membrane protein 11 (KMP11) is another Leishmania antigen and considered as the suitable candidate for vaccine development Leishmaniasis. It is a highly conserved surface protein expressed in both promastigotes and amastigotes. In this study, KMP11 and HASPB coding sequences were cloned into a pCDH-cGFP lentiviral vector as a fusion protein to be used as a DNA vaccine against L. major. The KMP11-HASPB fusion protein was successfully expressed as evidenced by RT-PCR and Western blot assays. The effect of the vaccine was determined by evaluating the level of IFN-γ, IL-10, IgG1, and IgG2a performed using ELISA as well as determining the parasite load after challenge with L. major in vaccinated mice. The results revealed that IFN-γ, IL-10, IgG1, and IgG2a significantly increased after vaccination using KMP11-HASPB-expressing lentiviruses in BALB/c mice. It is noteworthy that the level of IFN-γ and IgG2a was higher than that of IL-10 and IgG1, respectively, which indicates the activation Th1 cells, macrophages, and cellular immunity. Moreover, the parasite load in the spleen and lymph node of vaccinated mice after challenge was significantly lower than that of controls.

Systemic and local gut-specific antibody responses in preruminant calves sensitive to soya.

PubMed

Lallès, J P; Dréau, D; Huet, A; Toullec, R

1995-07-01

The systemic and local (gut) patterns of antibodies against various proteins from soyabean were analysed in preruminant calves fed milk substitutes based on skim milk powder (SMP) or heated soyabean flour (HSF) as the main protein sources. The titres of IgM, IgA, IgG1 and IgG2 antibodies were determined against feed extracts and purified soyabean proteins by dot-blotting in plasma after three months and jejunal mucous secretions after six months of feeding the experimental diets. The calves fed HSF had higher levels of circulating IgA, IgG1 and IgG2 antibodies against raw or heated soya extracts and purified proteins including alpha-conglycinin, beta-conglycinin, Bowman-Birk protease inhibitors and lectins than the calves fed SMP. In contrast, the differences between the IgM titres of the groups were most often not significant. The patterns of specific antibodies present in the jejunum were broadly similar to those observed in the blood, although the differences between the groups of calves more often reached significance for IgG2 and IgM than for IgA and IgG1, when the purified soyabean proteins were considered.

Commercial rodent diets differentially regulate autoimmune glomerulonephritis, epigenetics and microbiota in MRL/lpr mice

PubMed Central

Edwards, Michael R; Dai, Rujuan; Heid, Bettina; Cecere, Thomas E; Khan, Deena; Mu, Qinghui; Cowan, Catharine; Luo, Xin M; Ahmed, S Ansar

2017-01-01

Abstract The course and severity of lupus in spontaneous murine lupus models varies among laboratories, which may be due to variations in diet, housing and/or local environmental conditions. In this study, we investigated the influence of common rodent diets while keeping other factors constant. Female lupus-prone MRL/lpr (MRL/MpJ-Faslpr/J) mice were subjected to the same housing conditions and given one of the three diets: Teklad 7013 containing isoflavone-rich soy and alfalfa, Harlan 2018 isoflavone-rich soy-based diet or Research Diets Inc. D11112226 (RD) purified-ingredients diet containing casein and no phytoestrogens. While the total caloric intake was similar among all three treatment groups, mice fed on the 2018 diet developed higher levels of proteinuria and mice fed on either 7013 or 2018 developed higher levels of glomerular immune complex deposition. Remarkably, mice fed the RD diet had markedly decreased proteinuria with diminished C3, total IgG, IgG1 and IgG3 immune complex deposition, along with reduced CD11b+ cellular infiltration into the glomeruli. The type of diet intake also influenced cytokine production, fecal microbiota (increased Lachnospiraceae in mice fed on 2018), altered microRNAs (miRNAs; higher levels of lupus-associated miR-148a and miR-183 in mice fed on 7013 and/or 2018) and altered DNA methylation. This is the first study to comprehensively compare the cellular, molecular and epigenetic effects of these commercial diets in murine lupus. PMID:28637300

Vaccine specific immune response to an inactivated oral cholera vaccine and EPI vaccines in a high and low arsenic area in Bangladeshi children.

PubMed

Saha, Amit; Chowdhury, Mohiul I; Nazim, Mohammad; Alam, Mohammad Murshid; Ahmed, Tanvir; Hossain, Mohammad Bakhtiar; Hore, Samar Kumar; Sultana, Gazi Nurun Nahar; Svennerholm, Ann-Mari; Qadri, Firdausi

2013-01-11

Immune responses to the inactivated oral whole cell cholera toxin B (CTB) subunit cholera vaccine, Dukoral(®), as well as three childhood vaccines in the national immunization system were compared in children living in high and low arsenic contaminated areas in Bangladesh. In addition, serum complement factors C3 and C4 levels were evaluated among children in the two areas. VACCINATIONS: Toddlers (2-5 years) were orally immunized with two doses of Dukoral 14 days apart. Study participants had also received diphtheria, tetanus and measles vaccines according to the Expanded Program on Immunization (EPI) in Bangladesh. The mean level of arsenic in the urine specimens in the children of the high arsenic area (HAA, Shahrasti, Chandpur) was 291.8μg/L while the level was 6.60μg/L in the low arsenic area (LAA, Mirpur, Dhaka). Cholera specific vibriocidal antibody responses were significantly increased in the HAA (87%, P<0.001) and the LAA (75%, P<0.001) children after vaccination with Dukoral, but no differences were found between the two groups. Levels of CTB specific IgA and IgG antibodies were comparable between the two groups, whereas LPS specific IgA and IgG were higher in the LAA group, although response rates were comparable. Diphtheria and tetanus vaccine specific IgG responses were significantly higher in the HAA compared to the LAA group (P<0.001, P=0.048 respectively), whereas there were no differences in the measles specific IgG responses between the groups. Complement C3 and C4 levels in sera were higher in participants from the HAA than the LAA groups (P<0.001, P=0.049 respectively). The study demonstrates that the oral cholera vaccine as well as the EPI vaccines studied are immunogenic in children in high and low arsenic areas in Bangladesh. The results are encouraging for the potential use of cholera vaccines as well as the EPI vaccines in arsenic endemic areas. Copyright © 2012 Elsevier Ltd. All rights reserved.

The relationship between Toxoplasma gondii IgG antibodies and generalized anxiety disorder and obsessive-compulsive disorder in children and adolescents: a new approach.

PubMed

Akaltun, İsmail; Kara, Soner Sertan; Kara, Tayfun

2018-01-01

Toxoplasma gondii may play a role in the development of psychiatric diseases by affecting the brain. The purpose of this study was to examine the relation between serum toxoplasma IgG positivity and obsessive-compulsive disorder (OCD) and generalized anxiety disorder (GAD) in children and adolescents. Sixty patients diagnosed with OCD and 60 patients with GAD presenting to the pediatric psychiatry clinic, together with 60 control group subjects with no psychiatric diagnosis, were included in the study. The patients were administered the State-Trait Anxiety Inventory for Children and the Children's Yale-Brown Obsessive Compulsive Scale. Serum toxoplasma IgG levels were determined from blood specimens collected from the study and control groups. The results were then compared using statistical methods. State and trait anxiety levels were significantly higher in the OCD and GAD patients than in the control group (p = .0001/.0001). Serum toxoplasma IgG levels were positive in 21 (35%) of the OCD patients, 19 (31.7%) of the GAD patients and 6 (10%) of the control group. A significant relation was determined between IgG positivity and GAD (p = .003). IgG-positive individuals were determined to have a 4.171-fold greater risk of GAD compared to those without positivity (4.171[1.529-11.378]) (p = .005). A significant relation was also determined between IgG positivity and OCD (p = .001). IgG-positive individuals were determined to have a 4.846-fold greater risk of OCD compared to those without positivity (4.846[1.789-13.126]) (p = .002). This study shows that serum toxoplasma IgG positivity indicating previous toxoplasma infection increased the risk of GAD 4.171-fold and the risk of OCD 4.846-fold in children and adolescents. Further studies are now needed to investigate the relation between T. gondii infection and GAD/OCD and to determine the pathophysiology involved.

The effect of parenteral immunisation on antibody production in the pig colon.

PubMed

Rees, A S; Lysons, R J; Stokes, C R; Bourne, F J

1989-11-30

Local and systemic antibody production was studied in pigs to compare responses to live and killed bacterial antigen and purified protein antigen, with and without prior mucosal stimulation. Recovery from challenge with live bacteria and intramuscular injection with killed bacteria gave rise to similar high levels of serum IgG antibody, but the ratio of specific IgA to IgG in the colon was significantly higher after infection than following vaccination with killed bacteria. Vaccination with a protein antigen gave rise to serum and local antibody production. Prior feeding of the antigen had a tolerising effect on the serum antibody response, but production of IgG and IgA antibody by the colon was not suppressed.

T-cell-independent and T-cell-dependent antibody responses in patients with chronic renal failure.

PubMed

Beaman, M; Michael, J; MacLennan, I C; Adu, D

1989-01-01

Antibody responses against pneumococcal capsular antigens and tetanus toxoid were measured in 14 patients with chronic renal failure who were managed by continuous ambulatory peritoneal dialysis (CAPD) or haemodialysis (HD) and in eight healthy controls. IgG antipneumococcal responses were predominantly of the IgG2 and to a lesser extent IgG1 subclasses, while the IgG response against tetanus toxoid was largely IgG1 with smaller amounts of IgG4 and IgG3. The post-immunisation serum levels of IgG1 and IgM antibody against both antigens were significantly reduced in the uraemic patients compared with controls (P less than 0.05). All the uraemic patients had normal levels of IgG, IgA and IgM in the serum, but elevated levels of IgG3 prior to immunisation. The mechanisms responsible for the asymmetric depression of antibody responses in uraemia are unclear and may account in part for the increased susceptibility to infection in these patients.

Oral immunogenicity of tomato-derived sDPT polypeptide containing Corynebacterium diphtheriae, Bordetella pertussis and Clostridium tetani exotoxin epitopes.

PubMed

Soria-Guerra, Ruth E; Rosales-Mendoza, Sergio; Moreno-Fierros, Leticia; López-Revilla, Rubén; Alpuche-Solís, Angel G

2011-03-01

DPT vaccine, designed to immunize against diphtheria, pertussis, and tetanus, has been shown to be effective in humans. Nevertheless, dissatisfaction with the whole-cell preparations is due to the reactogenicity, which has to lead to the development of new safer formulations. Previously, we described the expression in tomato of a plant-optimized synthetic gene encoding the recombinant polypeptide sDPT, containing mainly immunoprotective epitopes of the diphtheria, pertussis and tetanus exotoxins and two adjuvants. In this study, we examined whether the ingestion of tomato-derived sDPT protein induces specific antibodies in mice after three weekly doses scheme. A positive group immunized with DPT toxoids was included. Specific antibody levels were assessed in serum, gut and lung. Sera tested for IgG antibody response to pertussis, tetanus and diphtheria toxin showed responses to the foreign antigens; interestingly, the response to diphtheria epitope was similar to those observed in the positive group. We found higher IgG1 than IgG2a responses in serum. A modest IgG response was observed in the tracheopulmonary fluid. High response of IgA against tetanus toxin was evident in gut, which was statistically comparable to that obtained in the positive group. The levels of response in these groups were higher than those in mice that received wild-type tomato. These findings support the concept of using transgenic tomatoes expressing sDPT polypeptide as model for edible vaccine against diphtheria, pertussis, and tetanus.

HIV-Exposed Infants Vaccinated with an MF59/Recombinant gp120 Vaccine Have Higher-Magnitude Anti-V1V2 IgG Responses than Adults Immunized with the Same Vaccine.

PubMed

McGuire, Erin P; Fong, Youyi; Toote, Christopher; Cunningham, Coleen K; McFarland, Elizabeth J; Borkowsky, William; Barnett, Susan; Itell, Hannah L; Kumar, Amit; Gray, Glenda; McElrath, M Julianna; Tomaras, Georgia D; Permar, Sallie R; Fouda, Genevieve G

2018-01-01

In the RV144 vaccine trial, IgG responses against the HIV envelope variable loops 1 and 2 (V1V2) were associated with decreased HIV acquisition risk. We previously reported that infants immunized with an MF59-adjuvanted rgp120 vaccine developed higher-magnitude anti-V1V2 IgG responses than adult RV144 vaccinees. To determine whether the robust antibody response in infants is due to differences in vaccine regimens or to inherent differences between the adult and infant immune systems, we compared Env-specific IgG responses in adults and infants immunized with the same MF59- and alum-adjuvanted HIV envelope vaccines. At peak immunogenicity, the magnitudes of the gp120- and V1V2-specific IgG responses were comparable between adults and infants immunized with the alum/MNrgp120 vaccine (gp120 median fluorescence intensities [FIs] in infants = 7,118 and in adults = 11,510, P = 0.070; V1V2 median MFIs of 512 [infants] and 804 [adults], P = 0.50), whereas infants immunized with the MF59/SF-2 rgp120 vaccine had higher-magnitude antibody levels than adults (gp120 median FIs of 15,509 [infants] and 2,290 [adults], P < 0.001; V1V2 median FIs of 23,926 [infants] and 1,538 [adults]; P < 0.001). Six months after peak immunogenicity, infants maintained higher levels Env-specific IgG than adults. Anti-V1V2 IgG3 antibodies that were associated with decreased HIV-1 risk in RV144 vaccinees were present in 43% of MF59/rgp120-vaccinated infants but only in 12% of the vaccinated adults ( P = 0.0018). Finally, in contrast to the rare vaccine-elicited Env-specific IgA in infants, rgp120 vaccine-elicited Env-specific IgA was frequently detected in adults. Our results suggest that vaccine adjuvants differently modulate gp120-specific antibody responses in adults and infants and that infants can robustly respond to HIV Env immunization. IMPORTANCE More than 150,000 pediatric HIV infections occur yearly, despite the availability of antiretroviral prophylaxis. A pediatric HIV vaccine could reduce the number of these ongoing infant infections and also prime for long-term immunity prior to sexual debut. We previously reported that immunization of infants with an MF59-adjuvanted recombinant gp120 vaccine induced higher-magnitude, potentially protective anti-V1V2 IgG responses than in adult vaccinees receiving the moderately effective RV144 vaccine. In the present study, we demonstrate that the robust response observed in infants is not due to differences in vaccine regimen or vaccine dose between adults and infants. Our results suggest that HIV vaccine adjuvants may differentially modulate immune responses in adults and infants, highlighting the need to conduct vaccine trials in pediatric populations. Copyright © 2017 American Society for Microbiology.

Low serum immunglobulin G (IgG) during nephrosis is a predictor of urinary tract infection (UTI) in children with nephrotic syndrome.

PubMed

Afroz, S; Roy, D K; Khan, A H

2013-04-01

Low serum level of IgG, complement C3 and C4 in nephrotic syndrome children may cause increased susceptibility to infection. Serum level of IgG and complements in nephrotic children (NS) with UTI has been analyzed in this cross sectional study. It was carried out in the department of Pediatric nephrology, National Institute of Kidney Diseases & Urology (NIKDU), Dhaka, Bangladesh. The study subjects were followed up prospectively for one year to see and compare the frequency of relapse of NS and UTI. Patients were selected in a nonrandom purposive technique. Nephrotic syndrome children with initial attack between 1-12 year of age were included over a period of one year. The patients were grouped into Group I - UTI positive and Group II - UTI negative depending on urine culture positivity and colony count >10⁵ CFU/ml. Serum IgG and complements C3, C4 levels were done in both groups during nephrosis and were compared. A total of 101 children M: F 1.7:1, mean age 5.96±3.2 years were included in this study. Group I, n=45 vs. Group II, n=56. The mean serum level of IgG was low in Group I (549.91±210.71 vs. 728.64±235.81mg/dl, p<0.001). Serum IgG level less than 700mg/dl was found in 37 vs. 23 children {x² (¹) 17.52 p<0.001, OR=6.63}. Mean serum complement C3 level was also low in Group I (123.09±40.52 vs. 143.38±37.06mg/dl, p<0.05). But complement C3 and C4 level do not carry any risk of developing UTI in nephrotic children. Higher number of children in Group II were at remission (n=24) during follow up, while frequent relapsers were high in Group I (n=22). Increased frequency of UTI attack (88 episodes) was found in Group I children compared to none in Group II during follow up. So low serum level of IgG in children with NS during nephrosis can predict UTI with an odds ratio of 6.63 as well as relapse. Serum level of C3, C4 do not associated with any risk of development of UTI in NS children.

Increased serum level of prolactin is related to autoantibody production in systemic lupus erythematosus.

PubMed

Yang, J; Li, Q; Yang, X; Li, M

2016-04-01

Prolactin (PRL) is known to aid effector B cells and augment autoimmunity, but the role of PRL in systemic lupus erythematosus (SLE) is not fully elucidated. The aim of this study was to determine the correlation between the serum levels of PRL and autoantibody production in SLE. Blood levels of PRL, anti-double-stranded DNA (ds-DNA) antibody, immunoglobulin M (IgM) and immunoglobulin G (IgG) were determined in samples from 30 adult patients with SLE and 25 healthy controls. The relationships between the serum level of PRL and SLE disease activity, as well as the titres of the ds-DNA antibody, IgM and IgG were determined. The serum level of PRL was higher in the SLE patients than in the healthy controls. PRL concentration increased during SLE flares-ups and decreased following disease remission. There was a positive correlation between the PRL concentration and serum levels of IgM, IgG and ds-DNA antibody titre. These data suggest that the serum level of PRL was closely related to the antibody production and disease activity of SLE patients. PRL concentration was dramatically reduced upon the remission of disease activity, indicating that PRL levels might be a promising predictor of SLE disease severity. © The Author(s) 2015.

Evaluation of De-O-Acetylated Meningococcal C Polysaccharide-Tetanus Toxoid Conjugate Vaccine in Infancy: Reactogenicity, Immunogenicity, Immunologic Priming, and Bactericidal Activity against O-Acetylated and De-O-Acetylated Serogroup C Strains

PubMed Central

Richmond, Peter; Borrow, Ray; Findlow, Jamie; Martin, Sarah; Thornton, Carol; Cartwright, Keith; Miller, Elizabeth

2001-01-01

The polysaccharide capsule of serogroup C Neisseria meningitidis (MenC) has been integral to vaccine development. Licensed MenC vaccines contain the O-acetylated (OAc+) form of polysaccharide. Some MenC strains have de-O-acetylated (OAc−) polysaccharide, which may affect antibody specificity and functional activity when used in a vaccine. We evaluated an OAc-MenC conjugate-tetanus toxoid conjugate (MCC-TT) vaccine given concomitantly with whole-cell diphtheria-tetanus-pertussis, Haemophilus influenzae type b, and oral polio immunization in 83 infants at 2, 3, and 4 months of age. Serum bactericidal activities (SBA) against OAc+ and OAc− MenC strains and OAc+ and OAc− polysaccharide-specific immunoglobulin G (IgG) levels were evaluated. MCC-TT vaccine was well tolerated. All infants produced SBA titers of ≥8 after a single dose at 2 months of age. The SBA geometric mean titer for OAc+ strain C11 increased from 2.7 (95% confidence interval [CI] 2.2 to 3.2) to 320 (95% CI, 237 to 432), 773 (95% CI, 609 to 982), and 1,063 (95% CI, 856 to 1319) after one, two, and three doses of MCC-TT, respectively. OAc− IgG levels were twice as high as OAc+ IgG levels after the primary series of MCC-TT vaccine, and the SBA was significantly higher against the OAc− MenC strain. Antibody responses to booster vaccination with either OAc+ MenC polysaccharide vaccine (MACP) or a fourth dose of MCC-TT at 14 months of age provided evidence of immunologic memory. The acetylation status of the booster vaccine influenced the specificity of the response, with significantly higher OAc− IgG levels and SBA after MCC-TT vaccine compared to MACP vaccine but similar OAc+ antibody levels. MCC-TT vaccine is highly immunogenic and primes for immunologic memory against OAc+ and OAc− MenC strains in infancy. PMID:11254596

Placental Malaria Induces Variant-Specific Antibodies of the Cytophilic Subtypes Immunoglobulin G1 (IgG1) and IgG3 That Correlate with Adhesion Inhibitory Activity

PubMed Central

Elliott, Salenna R.; Brennan, Amy K.; Beeson, James G.; Tadesse, Eyob; Molyneux, Malcolm E.; Brown, Graham V.; Rogerson, Stephen J.

2005-01-01

Antibodies targeting variant antigens on the surfaces of chondroitin sulfate A (CSA)-binding malaria-infected erythrocytes have been linked to protection against the complications of malaria in pregnancy. We examined the isotype/subtype profiles of antibodies that bound to variant surface antigens expressed by CSA-adherent Plasmodium falciparum in pregnant Malawian women with and without histologically defined placental malaria. Women in their first pregnancy with placental malaria produced significantly greater amounts of immunoglobulin G1 (IgG1) and IgG3 reactive with surface antigens of malaria-infected erythrocytes than uninfected women of the same gravidity. IgG1 and IgG3 levels in infected and control women in later pregnancies were similar to those in infected women in their first pregnancy. Levels of IgG2 and IgG4 were similarly low in infected and uninfected women of all gravidities. IgM that bound to the surface of CSA-adherent P. falciparum occurred in all groups of women and malaria-naïve controls. There was a significant correlation between IgG1 and IgG3 levels, indicating that women usually produced both subtypes. Levels of IgG1 and IgG3 correlated with the ability of serum or plasma to inhibit parasite adhesion to CSA. Taken together, these data suggest that IgG1 and IgG3 dominate the IgG response to placental-type variant surface antigens. They may function by blocking parasite adhesion to placental CSA, but given their cytophilic nature, they might also opsonize malaria-infected erythrocytes for interaction with Fc receptors on phagocytic cells. PMID:16113309

Differential Decline in Leishmania Membrane Antigen-Specific Immunoglobulin G (IgG), IgM, IgE, and IgG Subclass Antibodies in Indian Kala-Azar Patients after Chemotherapy

PubMed Central

Anam, Khairul; Afrin, Farhat; Banerjee, Dwijadas; Pramanik, Netai; Guha, Subhasis K.; Goswami, Rama P.; Saha, Shiben K.; Ali, Nahid

1999-01-01

Pathogenesis in kala-azar is associated with depressed cellular immunity and significant elevation of antileishmanial antibodies. Since these antibodies are present even after cure, analysis of the parasite-specific isotypes and immunoglobulin G (IgG) subclasses in kala-azar patients may shed new light on the immune responses during progression and resolution of infection. Using leishmanial membrane antigenic extracts, we investigated the relative levels of specific IgG, IgM, IgA, IgE, and IgG subclasses in Indian kala-azar patient sera during disease, drug resistance, and cure. Acute-phase sera showed strong stimulation of IgG, followed by IgE and IgM and lastly by IgA antibodies. IgG subclass analysis revealed expression of all of the subclasses, with a predominance of IgG1 during disease. Following sodium stibogluconate (SAG) resistance, the levels of IgG, IgM, IgE, and IgG4 remained constant, while there was a decrease in the titers of IgG2 and IgG3. In contrast, a significant (2.2-fold) increase in IgG1 was observed in these individuals. Cure, in both SAG-responsive and unresponsive patients, correlated with a decline in the levels of IgG, IgM, IgE, and all of the IgG subclasses. The stimulation of IgG1 and the persistence, most importantly, of IgE and IgG4 following drug resistance, along with a decline in IgE, IgG4, and IgG1 with cure, demonstrate the potential of these isotypes as possible markers for monitoring effective treatment in kala-azar. PMID:10569788

Monoclonal IgG in MGUS and multiple myeloma targets infectious pathogens

PubMed Central

Bosseboeuf, Adrien; Feron, Delphine; Tallet, Anne; Rossi, Cédric; Charlier, Cathy; Garderet, Laurent; Caillot, Denis; Moreau, Philippe; Cardó-Vila, Marina; Pasqualini, Renata; Nelson, Alfreda Destea; Wilson, Bridget S.; Perreault, Hélène; Piver, Eric; Weigel, Pierre; Harb, Jean; Bigot-Corbel, Edith; Hermouet, Sylvie

2017-01-01

Subsets of mature B cell neoplasms are linked to infection with intracellular pathogens such as Epstein-Barr virus (EBV), hepatitis C virus (HCV), or Helicobacter pylori. However, the association between infection and the immunoglobulin-secreting (Ig-secreting) B proliferative disorders remains largely unresolved. We investigated whether the monoclonal IgG (mc IgG) produced by patients diagnosed with monoclonal gammopathy of undetermined significance (MGUS) or multiple myeloma (MM) targets infectious pathogens. Antigen specificity of purified mc IgG from a large patient cohort (n = 244) was determined using a multiplex infectious-antigen array (MIAA), which screens for reactivity to purified antigens or lysates from 9 pathogens. Purified mc IgG from 23.4% of patients (57 of 244) specifically recognized 1 pathogen in the MIAA. EBV was the most frequent target (15.6%), with 36 of 38 mc IgGs recognizing EBV nuclear antigen-1 (EBNA-1). MM patients with EBNA-1–specific mc IgG (14.0%) showed substantially greater bone marrow plasma cell infiltration and higher β2-microglobulin and inflammation/infection–linked cytokine levels compared with other smoldering myeloma/MM patients. Five other pathogens were the targets of mc IgG: herpes virus simplex-1 (2.9%), varicella zoster virus (1.6%), cytomegalovirus (0.8%), hepatitis C virus (1.2%), and H. pylori (1.2%). We conclude that a dysregulated immune response to infection may underlie disease onset and/or progression of MGUS and MM for subsets of patients. PMID:28978808

Indices of anti-dengue immunoglobulin G subclasses in adult Mexican patients with febrile and hemorrhagic dengue in the acute phase.

PubMed

Posadas-Mondragón, Araceli; Aguilar-Faisal, José Leopoldo; Chávez-Negrete, Adolfo; Guillén-Salomón, Edith; Alcántara-Farfán, Verónica; Luna-Rojas, Lucero; Ávila-Trejo, Amanda Marineth; Del Carmen Pacheco-Yépez, Judith

2017-10-01

Heterologous secondary infections are at increased risk of developing dengue hemorrhagic fever (DHF) because of antibody-dependent enhancement (ADE). IgG subclasses can fix and activate complement and bind to Fcɣ receptors. These factors may also play an important role in the development of ADE and thus in the pathogenesis of DHF. The aim of this study was to analyze the indices of anti-dengue IgG subclasses in adult patients with febrile and hemorrhagic dengue in the acute phase. In 2013, 129 patients with dengue fever (DF) and 57 with DHF in Veracruz, Mexico were recruited for this study and anti-dengue IgM and IgG determined by capture ELISA. Anti-dengue IgG subclasses were detected by indirect ELISA. Anti-dengue IgG2 and IgG3 subclasses were detected in patients with dengue. IgG1 increased significantly in the sera of patients with both primary and secondary infections and DHF, but was higher in patients with secondary infections. The IgG4 subclass index was significantly higher in the sera of patients with DHF than in that of those with DF, who were in the early and late acute phase of both primary and secondary infection. In conclusion, indices of subclasses IgG1 and IgG4 were higher in patients with DHF. © 2017 The Societies and John Wiley & Sons Australia, Ltd.

Autoantibody against matrix metalloproteinase-3 in patients with systemic sclerosis.

PubMed

Nishijima, C; Hayakawa, I; Matsushita, T; Komura, K; Hasegawa, M; Takehara, K; Sato, S

2004-11-01

Systemic sclerosis (SSc) is characterized by multi-organ fibrosis with an autoimmune background. Although autoantibodies are detected frequently in SSc patients, the role of autoantibody in the development of fibrosis remains unknown. Connective tissue homeostasis is a balance between the synthesis and degradation of the extracellular matrix (ECM); ECM degradation is regulated mainly by matrix metalloproteinases (MMPs). Anti-MMP-1 antibody is suggested to inhibit MMP-1 and be involved in the development of the fibrosis in SSc. However, the accumulation of various ECM components in the tissue of SSc cannot be explained by the anti-MMP-1 antibody alone. In this study, we examined the presence or levels of antibody to MMP-3, a protein which degrades various ECM components relevant to SSc fibrosis. Enzyme-linked immunosorbent assay (ELISA) using human recombinant MMP-3 revealed that IgG anti-MMP-3 autoantibody levels were elevated significantly in the sera from SSc patients, but not in patients with active systemic lupus erythematosus or dermatomyositis. IgG and IgM anti-MMP-3 antibody levels were significantly higher in diffuse cutaneous SSc, a severe form, than those in limited cutaneous SSc. Consistently, IgG anti-MMP-3 antibody levels correlated significantly with fibrosis of the skin, lung and renal blood vessels. The presence of IgG anti-MMP-3 autoantibody in sera from SSc patients was confirmed by immunoblotting analysis. Remarkably, MMP-3 activity was inhibited by IgG anti-MMP-3 antibody. These results suggest that anti-MMP-3 antibody is a serological marker that reflects the severity of SSc and also suggest that it may contribute to the development of fibrosis by inhibiting MMP-3 activity and reducing the ECM turnover.

Increased insulin-like growth factor-1 levels in cerebrospinal fluid of advanced subacute sclerosing panencephalitis patients.

PubMed

Yılmaz, Deniz; Yüksel, Deniz; Gökkurt, Didem; Oguz, Hava; Anlar, Banu

2016-07-01

Subacute sclerosing panencephalitis (SSPE) is a progressive, lethal disease. Brain histopathology in certain SSPE patients shows, neurofibrillary tangles composed of abnormally phosphorylated, microtubule-associated protein tau (PHF-tau). Because the, phosphorylation of tau is inhibited by insulin and insulin-like growth factor-1 (IGF-1), we investigated cerebrospinal fluid (CSF) insulin and IGF-1 levels in SSPE patients. In this study CSF IGF-1 and insulin levels of 45 SSPE and 25 age-matched control patients were investigated. CSF IGF-1 levels were significantly higher in SSPE patients at stage 4, compared to other stages (p 0.05). CSF insulin and IGF-1 levels were both positively correlated with serum measles IgG. The correlation between CSF insulin and IGF-1 levels and serum measles virus IgG titer may be the result of, insulin activating IGF-1 receptors, and consequently, IGF-1 stimulating, plasma cells and enhancing IgG production. Increased IGF-1 may also, inhibit the phosphorylation of tau. Further studies examining the, correlation between IGF-1, insulin, tau, and PHF-tau levels in the same, patients may clarify any possible pathogenetic relation between these, pathways. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Immune Status 'in Children with Beta Thalassemia' in Correlation 'with Iron Overload': Single Center Egyptian Study.

PubMed

Hagag, Adel A; Elgamsy, Mohamed A; El-Asy, Hassan M; Gamal, Rasha M; Elshahaby, Walid N; Abd Elbar, Enaam S

2016-01-01

'Beta thalassemia is inherited hemoglobin disorder resulting in chronic hemolytic anemia that requires lifelong transfusion therapy'. 'Repeated blood transfusions and RBCs hemolysis are the main causes of iron overload', which in addition to immune abnormalities, are common predisposing factors to infections in patients with thalassemia. The Aim of this Work: The aim of this work was to study immune status including T lymphocyte subsets and serum immunoglobulin levels 'in children with beta- thalassemia in correlation with iron overload'. The present 'study was conducted on 40 children with beta thalassemia major under follow up at Hematology Unit, Pediatric Department, Tanta University' 'including 24 males and 16 females with mean' age value of 9. 22 ± 3.9 years and 20 'healthy children of matched age and sex as a control group'. All children included in the study were subjected to; 'complete blood count, Hb electrophoresis, serum iron status', T cell subsets including CD3, CD4 and CD8 and serum immunoglobulin levels including IgM, IgA and IgG. 'Pallor and jaundice were the most common presenting' clinical manifestations. Infective episodes 'were significantly higher in patients' compared with controls. There were significantly lower Hb, MCV and MCH levels and significantly higher WBCs and platelets counts, reticulocytes and lymphocytes percentage in patients than controls and no significant differences in MCHC between patients and controls. Serum ferritin and iron were 'significantly higher but TIBC was significantly lower in' patients than controls. CD3, CD4 and IgM were significantly lower but CD8, IgG, and IgA 'were significantly higher in patients than controls' with negative correlation between CD3, CD4, IgM and ferritin and positive correlation between CD8, IgG, IgA and ferritin. Iron overload can affect humeral and cell mediated immunity in patients with beta thalassemia with reduction of IgM, CD3 and CD4 and elevation of CD8, IgG, and IgA. Regular follow up of patients with beta thalassemia for detection of iron overload as it affects humeral and cell mediated immunity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

IgG subclass antibodies to human and bacterial HSP60 are not associated with disease activity and progression over time in axial spondyloarthritis

PubMed Central

2013-01-01

Introduction Spondyloarthritis (SpA), an interrelated group of rheumatic diseases, has been suggested to be triggered by bacterial infections prior to the development of an autoimmune response that causes inflammation of the spinal and peripheral joints. Because human heat shock protein 60 (HSP60), recently renamed HSPD1, and bacterial HSP60 are highly homologous, immunological cross-reactivity has been proposed as a mechanism of disease initiation. However, previous investigations of the humoral immune response to HSP60 in SpA patients have lacked determination of immunoglobulin G (IgG) subclasses and patient follow-up. In this study, we have focused on these parameters in a cohort of axial SpA patients with a well-established set of clinical characteristics, including MRI changes and human leukocyte antigen B27. Methods IgG subclass antibodies (IgG1, IgG2, IgG3 and IgG4) against recombinant HSP60 of three reactive arthritis-related bacteria; human HSP60; and the microorganisms Chlamydia trachomatis and C. pneumoniae were determined by ELISA. Serum samples collected from 2004 to 2006 and in 2010 and 2011 from 39 axial SpA patients were analyzed and compared with samples from 39 healthy controls. The Mann-Whitney U test and Wilcoxon matched pairs test were used to compare the antibody levels in different and paired groups, respectively. P < 0.01 was considered significant. The Spearman nonparametric correlation was used to determine correlation between antibody levels and between antibody levels and the disease parameters. Results Elevated levels of IgG1 and IgG3 to human HSP60 and IgG1 to HSP60 of Salmonella enterica Enteritidis were observed in SpA patients compared with healthy controls at both time points. The antibody levels were almost constant over time for IgG1, whereas high levels of IgG3 to human HSP60 tended to decrease over time. The antibody response to human HSP60 was predominantly of the IgG3 subclass, and patients with high levels of IgG3 to this antigen had low levels of IgG1, indicating an inverse association. Different IgG subclasses were produced against bacterial and human HSP60 in the same serum sample, IgG1 and IgG3, respectively, indicating that there was no cross-reaction. Conclusions A significant association was observed between axial SpA and the presence of IgG1/IgG3 antibodies to human HSP60 and of IgG1 to S. enterica Enteritidis and C. trachomatis. Generation of antibodies to human HSP60 was independent of the presence of antibodies to bacterial HSP60. No association was observed between clinical and MRI changes with antibodies over time. Altogether, such antibodies do not reflect the disease activity in these patients. This study has been approved by the Regional Research Ethics Committee of Central Jutland, Denmark. Trial registration numbers: 20050046 and 20100083 PMID:23705835

Effect of dietary manipulation and vaccination of turkey breeder hens on immunoglobulin levels of yolk, yolk sac and neonate poults.

PubMed

Bhattacharyya, A; Majumdar, S; Bhanja, S K; Mandal, A B; Dash, B B

2018-04-01

Two hundred turkey breeder hens and 24 viable toms of 30-35 weeks age of small white variety were distributed into two treatment groups having four replicates of 25 hens and three toms in each treatment. First four replicates were offered a turkey breeder diet (Diet A) (Nutrient requirements of poultry, 1994, National Academic Press, Washington, DC) and the rest four replicates were maintained on a higher plane of nutrition (Diet B) for 8-week duration. After 6 weeks of experimental feeding, two replicates from each treatment groups were vaccinated with ND (R 2 B) vaccine. Yolk sac of embryo from birds fed Diet B had a significantly higher (p < .05) IgG, IgM level and HI titre (log 2) than those fed Diet A. HI titre values of embryonic yolk sac from the vaccinated birds fed Diet B were significantly higher (p < .05) than that of the control groups. In addition, HI titre values were significantly higher (p < .05) in the day-old poults of the birds fed Diet B than that of those fed Diet A. There was significantly (p < .01) positive correlation between serum IgG and IgM of the breeder birds and day-old chicks. Similarly, there was significantly (p < .05) positive correlation between yolk IgG and IgM after 1-month experimental feeding and yolk sac IgG and IgM. Positive correlation (p < .05) also existed between yolk sac IgM and day-old chick serum IgM. Furthermore, the HI titres of breeder birds' serum at 14 days post-vaccination were positively correlated with their egg yolk after 10 and 15 days post-vaccination, yolk sac and day-old chicks. Thus, the study envisaged that a higher immunity in neonate poults from turkey breeders maintained on a higher plane of nutrition may be elicited as there was maternal transfer of antibodies from the serum of breeder birds to their offsprings through their yolk sac. © 2018 Blackwell Verlag GmbH.

Effect of Chronic Social Stress on Prenatal Transfer of Antitetanus Immunity in Captive Breeding Rhesus Macaques (Macaca mulatta).

PubMed

Stammen, Rachelle L; Cohen, Joyce K; Meeker, Tracy L; Crane, Maria M; Amara, Rama R; Hicks, Sakeenah L; Meyer, Jerrold S; Ethun, Kelly F

2018-05-15

Because tetanus can cause significant morbidity and mortality in NHP, colonywide vaccination with tetanus toxoid is recommendedfor outdoor breeding colonies of rhesus macaques, with primary immunizations commonly given to infants at 6 mo of age followed by booster vaccines every 10 y. Maternal antibodies are thought to offer protective immunity to infants younger than 6 mo. However, historical colony data from the Yerkes National Primate Research Center show a higher incidence of tetanus among infants (≤ 6 mo old) born to subordinate dams. Whether this higher incidence of infantile tetanus is due to a higher incidence of trauma among subordinate animals or is a stress-induced impairment of maternal antibody protection is unknown. Studies in other NHP species suggest that chronic exposure to social stressors interferes with the receptor-mediated transplacental transfer of IgG. Therefore, the primary aim of this study was to determine whether chronic stress associated with social subordination impairs prenatal transfer of antitetanus immunity in breeding female rhesus macaques. Subjects included 26 high- and 26 low-ranking adult female rhesus macaques that were nearly 5 or 10 y after their initial immunization and their nonimmunized infants. We hypothesized that infants born to subordinate dams that were nearly 10 y after immunization would have the lowest infant-to-dam antibody ratios and thus would be at greatest risk for infection. Results revealed no significant intergroup differences in infant antitetanus IgG levels. However, infant-to-dam IgG ratios against tetanus were significantly lower among subordinate animals compared with dominant macaques, after accounting for the number of years since the dam's initial vaccination. In addition, higher maternal hair cortisol levels predicted lower infant-to-dam tetanus toxoid IgG ratios. Together, these findings suggest that chronic social stress in female rhesus macaques may hamper the prenatal transfer of antitetanus immunity to offspring.

Effects of type I/type II interferons and transforming growth factor-beta on B-cell differentiation and proliferation. Definition of costimulation and cytokine requirements for immunoglobulin synthesis and expression.

PubMed

Estes, D M; Tuo, W; Brown, W C; Goin, J

1998-12-01

In this report, we sought to determine the role of selected type I interferons [interferon-alpha (IFN-alpha) and interferon-tau (IFN-tau)], IFN-gamma and transforming growth factor-beta (TGF-beta) in the regulation of bovine antibody responses. B cells were stimulated via CD40 in the presence or absence of B-cell receptor (BCR) cross-linking. IFN-alpha enhanced IgM, IgG2 and IgA responses but did not enhance IgG1 responses. BCR signalling alone was more effective at inducing IgG2 responses with IFN-alpha than dual cross-linking with CD40. Recombinant ovine IFN-tau was less effective at inducing IgG2 responses when compared with IFN-alpha, though IgA responses were similar in magnitude following BCR cross-linking. At higher concentrations, IFN-tau enhanced IgA responses greater than twofold over the levels observed with IFN-alpha. Previous studies have shown that addition of IFN-gamma to BCR or pokeweed mitogen-activated bovine B cells stimulates IgG2 production. However, following CD40 stimulation alone, IFN-gamma was relatively ineffective at stimulating high-rate synthesis of any non-IgM isotype. Dual cross-linking via CD40 and the BCR resulted in decreased synthesis of IgM with a concomitant increase in IgA and similar levels of IgG2 production to those obtained via the BCR alone. We also assessed the effects of endogenous and exogenous TGF-beta on immunoglobulin synthesis by bovine B cells. Exogenous TGF-beta stimulates both IgG2 and IgA production following CD40 and BCR cross-linking in the presence of IL-2. Blocking endogenous TGF-beta did not inhibit the up-regulation of IgG2 or IgA by interferons.

[Determination of cytomegalovirus IgG synthesis by the albumin correction in the aqueous humor of posner-schlossmann syndrome].

PubMed

Wang, X L; Wang, Z J; Tang, L; Cao, W W; Sun, X H

2017-02-11

Objective: To evaluate the usefulness of albumin correction in determination of cytomegalovirus IgG in the aqueous humor of Posner-Schlossman syndrome (PSS) patients. Methods: Cases series studies. Forty-two patients (26 men and 16 women) who were diagnosed as PSS were enrolled from Oct. 2009 to Oct. 2015 at the Eye and ENT Hospital. During the same period, 20 patients with primary open-angle glaucoma (POAG) and 30 patients with bacterial endophthalmitis or retinal necrosis were enrolled as negative control group and inflammatory disease control group, respectively. Aqueous humor and serum samples were assayed to detect CMV IgG by enzyme-linked immunosorbent assay (ELISA), and albumin by scattering immunonephelometry. CMV DNA in aqueous humor was assayed by polymerase chain reaction (PCR). The ratio which was calculated as the (aqueous humor CMV IgG/serum CMV IgG)/(aqueous humor concentration of albumin/serum albumin concentration) over 0.6 was considered as intraocular antibody formation. Performance of differentiating control eyes from eyes with CMV-positive PSS was evaluated by the receiver operating characteristic curve. The ANOVA test, Mann-Whitney test and Chi-square test were performed to compare the differences among groups. Results: The detectable rate of CMV IgG antibody in the aqueous humor was 76.2%, 100.0% and 10.0% in PSS, inflammatory disease control and POAG groups, respectively. The levels of CMV IgG antibody in the PSS groups were significantly higher than that of POAG groups ( Z= 4.23, P< 0.001).The positive rate corrected by the albumin was 71.4%, 3.3% and 0.0%.The corrected positive rate in PSS groups was significantly higher than that of the inflammatory disease control and POAG groups (χ(2)=30.38, P< 0.01; χ(2)= 24.89, P< 0.01), with a sensitivity of 75.0% and a specificity of 98.0%. The area under the curve for calibrated ratio was 0.942 (95% CI : 0.859 to 0.984) which was higher than that of CMV IgG ( Z= 6.19, P< 0.001).The corrected positive rate of CMV IgG antibody (71.4%) was higher than that of CMV DNA (47.6%, χ(2)=4.003, P= 0.045). Conclusions: CMV IgG antibody ratio which was corrected by aqueous humor and serum albumin could effectively improve aqueous antibody specificity in PSS patients. Furthermore, CMV IgG antibody ratio combined with PCR could improve the sensitivity of CMV detection. All of which help clarify the CMV infection in PSS in CMV DNA negative eyes. (Chin J Ophthalmol, 2017, 53: 104-108) .

Antibody response to the Haemophilus influenzae type b-tetanus toxoid conjugate vaccine in healthy and infection-prone individuals with IgG3 subclass deficiency.

PubMed

Hahn-Zoric, M; Ulanova, M; Friman, V; Björkander, J; Oxelius, V A; Lucas, A; Hanson, L A

2004-09-01

Searching for a possible explanation for the phenotypic heterogeneity in IgG3 deficiency, we studied the antibody response to a polysaccharide and a protein antigen in IgG3-deficient (IgG3d) adults after vaccination with Haemophilus influenzae type b capsular polysaccharide (Hib CP) conjugated to tetanus toxoid. Distribution of isotypes, idiotypes, clonotypes, and Gm allotypes were compared. All the vaccinated individuals, irrespective of the level of IgG3 and proneness to infections, developed protective levels of anti-Hib CP. Significantly lower prevaccination levels of IgG2 (p < 0.05) and IgG4 anti-Hib CP (p < 0.04 and p < 0.03) were noted among the infection-prone compared to the healthy IgG3d individuals and/or controls. Seventy percent of the IgG3d patients and none of the controls had the low responding Gm(ga-n/ga-n) genotype, while the majority of the controls had the alternative Gm(bfn/bfn) genotype. The conjugate ACT-HIB vaccine efficiently overcomes the IgG3 subclass deficiency state and the genetic predisposition for lower responsiveness, providing protection against Hib and tetanus infections. The proneness to infection in some IgG3d individuals may relate to their low prevaccination antibody levels.

Mucosal and systemic immune responses elicited by recombinant Lactococcus lactis expressing a fusion protein composed of pertussis toxin and filamentous hemagglutinin from Bordetella pertussis.

PubMed

Torkashvand, Ali; Bahrami, Fariborz; Adib, Minoo; Ajdary, Soheila

2018-05-05

We constructed a food-grade expression system harboring a F1S1 fusion protein of Bordetella pertussis to be produced in Lactococcus lactis NZ3900 as a new oral vaccine model against whooping cough, caused by B. pertussis. F1S1 was composed of N-terminally truncated S1 subunit of pertussis toxin and type I immunodominant domain of filamentous hemagglutinin which are both known as protective immunogens against pertussis. The recombinant L. lactis was administered via oral or intranasal routes to BALB/c mice and the related specific systemic and mucosal immune responses were then evaluated. The results indicated significantly higher levels of specific IgA in the lung extracts and IgG in sera of mucosally-immunized mice, compared to their controls. It was revealed that higher levels of IgG2a, compared to IgG1, were produced in all mucosally-immunized mice. Moreover, immunized mice developed Th1 responses with high levels of IFN-γ production by the spleen cells. These findings provide evidence for L. lactis to be used as a suitable vehicle for expression and delivery of F1S1 fusion protein to mucosa and induction of appropriate systemic and mucosal immune responses against pertussis. Copyright © 2018 Elsevier Ltd. All rights reserved.

Thyrotropin Receptor Antibody (TRAb)-IgM Levels Are Markedly Higher Than TRAb-IgG Levels in Graves' Disease Patients and Controls, and TRAb-IgM Production Is Related to Epstein-Barr Virus Reactivation.

PubMed

Kumata, Keisuke; Nagata, Keiko; Matsushita, Michiko; Kuwamoto, Satoshi; Kato, Masako; Murakami, Ichiro; Fukata, Shuji; Hayashi, Kazuhiko

2016-10-01

Graves' disease is an autoimmune thyroid disorder that mainly presents as hyperthyroidism and is caused by thyrotropin receptor antibodies (TRAbs) that stimulate thyroid-stimulating hormone receptors. We previously reported that Graves' disease patients and healthy controls both had Epstein-Barr virus (EBV)-infected TRAb-positive B cells and the EBV-reactivated induction of these B cells in cultures may induce the production of TRAbs. In the present study, we quantified serum TRAb-IgG and TRAb-IgM levels in 34 Graves' disease patients and 15 controls using ELISA to elucidate the mechanisms underlying EBV-related antibody production. As expected, TRAb-IgG and TRAb-IgM levels were higher in Graves' disease patients than in controls; however, TRAb-IgM levels were significantly higher than those of TRAb-IgG levels, whereas total IgM levels were lower than total IgG levels. On the other hand, the enhanced production of TRAb-IgM was frequently observed in patients with EBV reactivation. These results are consistent with the fact that the percentage of autoreactive IgM B cells are higher than that of autoreactive IgG B cells, and support the EBV-related polyclonal B cell activation. It is necessary to clarify the biological characteristics of TRAb-IgM and the relationship between TRAb isotypes and the biology of Graves' disease.

Predominate HIV1-specific IgG activity in various mucosal compartments of HIV1-infected individuals.

PubMed

Lü, F X

2000-10-01

Evaluating mucosal humoral immunity is important for understanding local immunity induced by HIV infection or vaccination and designing prophylactic strategies. To characterize the mucosal humoral immunity following HIV infection, the levels of immunoglobulins (Igs), antibodies (Abs), and HIV1-specific Ab activity were evaluated in cervicovaginal secretions (CVS), saliva, breast milk, and sera of HIV-infected individuals. HIV1-specific IgG activity was significantly higher than that of IgA in CVS, saliva, and breast milk. The highest HIV1-specific IgG activity was found in breast milk. The data suggest that anti-HIV1 Abs in CVS were most likely serum derived. However, HIV1-specific Abs in saliva and breast milk were mainly locally produced. The prevalence of HIV1-specific Abs in seropositive subjects was 97% for IgG and 95% for IgA in CVS, 100% for IgG and 80% for IgA in saliva, and 59% for IgG and 94% for IgA in breast milk. These data provide evidence for both a better understanding of the nature of humoral mucosal responses after HIV1 infection and the development of strategies to induce desirable functional mucosal immunity for preventing HIV transmission. Copyright 2000 Academic Press.

Subclass distribution of IgG antibodies to the rat oesophagus stratum corneum (so-called anti-keratin antibodies) in rheumatoid arthritis.

PubMed Central

Vincent, C; Serre, G; Basile, J P; Lestra, H C; Girbal, E; Sebbag, M; Soleilhavoup, J P

1990-01-01

Serum IgG, labelling the stratum corneum of the rat oesophagus epithelium, so-called anti-keratin antibodies (AKA) constitute the most specific marker for the diagnosis of rheumatoid arthritis. In this study, we investigated 31 IgG AKA-positive rheumatoid sera and 21 control sera from patients with non-rheumatoid inflammatory rheumatic diseases. The serum level of IgG1,2,3 and 4 was determined by radial immunodiffusion and the subclass distribution of IgG AKA by a three-step semi-quantitative immunofluorescence assay using standard monoclonal antibodies specific for each of the four human IgG subclasses. In the rheumatoid sera, the serum level of IgG1 was found to be significantly increased and the level of IgG2 significantly decreased with regard to the control sera, while the levels of IgG3 and 4 as well as total IgG were in the normal range. IgG1,2,3, and 4 AKA were detected in 27 (87%), 6 (19%), 4 (13%) and 11 (35%) of the 31 rheumatoid sera, respectively, and were found to be independent of the clinical and biological indices of the disease. In spite of inter-individual heterogeneity, two predominant profiles were distinguished: IgG1 (alone) and IgG(1 + 4), which together represented 18 sera (58%). The large predominance of IgG1 AKA and the quasi-absence of IgG2 AKA suggest that the recognized antigen may be partly comprised of protein. Moreover, the high frequency of occurrence of IgG4 AKA might result from chronic exposure to the eliciting antigen, which could be a genuine autoantigen since we demonstrated that it is also present in the stratum corneum of human epidermis. Images Fig. 1 PMID:1696185

Total and Toxocara canis larval excretory/secretory antigen- and allergen-specific IgE in atopic and non-atopic dogs.

PubMed

Zwickl, Lena L M N; Joekel, Deborah E; Fischer, Nina M; Rostaher, Ana; Thamsborg, Kristian; Deplazes, Peter; Favrot, Claude

2018-06-01

Total IgE concentrations are higher in dogs than in humans. Persistent Toxocara canis larval infection is prevalent in dogs and is associated with substantial specific antibody reactions. A correlation, however, between total IgE and T. canis-specific antibody levels in dogs has not been evaluated. To determine the relationship between total IgE, T. canis-specific IgG and IgE, and allergen-specific IgE levels in atopic and non-atopic dogs, and to evaluate possible confounding factors. Sera of 30 atopic and 30 non-atopic client-owned dogs. Total IgE, T. canis-specific antibody and allergen-specific IgE levels were evaluated by ELISA. Total IgE, T. canis-specific antibody and allergen-specific IgE levels were significantly higher in non-atopic compared to atopic dogs. A positive correlation was demonstrated between T. canis-specific IgG and T. canis-specific IgE; T. canis-specific IgG and total IgE; T. canis-specific IgE and total IgE; and allergen-specific IgE and total IgE. No differences were detected on the basis of age, gender, vaccination status; deworming or season between atopic and non-atopic dogs. Previous immunomodulatory treatment and cause of atopy did not influence antibody levels of atopic dogs. Toxocara canis-specific IgE appears to be a major component of total IgE in dogs. Total and T. canis-specific IgE levels are higher in non-atopic compared to atopic dogs. It is speculated that T. canis infection may have a protective effect against the development of canine atopic dermatitis and/or that elevations in total serum IgE level are often not associated with atopic dermatitis. © 2018 ESVD and ACVD.

IgG and IgE antibodies to Chironomidae in asthmatic patients.

PubMed Central

Yamashita, N; Ito, K; Nakagawa, T; Haida, M; Okudaira, H; Nakada, S; Miyamoto, T; Shibuya, T; Kamei, K; Sasa, M

1987-01-01

IgG antibodies to Chironomidae and its correlations to radioallergosorbent and skin reactions were examined with the aim of clarifying the relationship between asthma and Chironomidae. The level of specific IgG antibody in asthmatic patients (0.698 +/- 0.034, n = 104) was significantly greater than that in normal subjects (0.367 +/- 0.032, n = 52) (P less than 0.01). The specific IgG level was not correlated to skin reaction, nor to IgE RAST scores. Specific IgG1 and IgG4 levels in asthmatic patients were significantly greater than in control subjects (n = 14) (P less than 0.01). Images Fig. 5 PMID:3652516

IgG4 plasma cell myeloma: new insights into the pathogenesis of IgG4-related disease.

PubMed

Geyer, Julia T; Niesvizky, Ruben; Jayabalan, David S; Mathew, Susan; Subramaniyam, Shivakumar; Geyer, Alexander I; Orazi, Attilio; Ely, Scott A

2014-03-01

IgG4-related disease is a newly described systemic fibroinflammatory process, characterized by increase in IgG4-positive plasma cells. Its pathogenesis, including the role of IgG4, remains poorly understood. Plasma cell myeloma is typically associated with a large monoclonal serum spike, which is frequently of IgG isotype. We sought to identify and characterize a subset of IgG4-secreting myeloma, as it may provide a biological model of disease with high serum levels of IgG4. Six out of 158 bone marrow biopsies (4%) from patients with IgG myeloma expressed IgG4. Four patients were men and two were women, with a mean age of 64 (range 53-87) years. Imaging showed fullness of pancreatic head (1), small non-metabolic lymphadenopathy (1), and bone lytic lesions (6). Two patients developed necrotizing fasciitis. All had elevated serum M-protein (mean 2.4, range 0.5-4.2 g/dl), and none had definite signs or symptoms of IgG4-related disease. Four myelomas had plasmablastic morphology. Four had kappa and two had lambda light chain expression. Three cases expressed CD56. Two patients had a complex karyotype. In conclusion, the frequency of IgG4 myeloma correlates with the normal distribution of IgG4 isoform. The patients with IgG4 myeloma appear to have a high rate of plasmablastic morphology and could be predisposed to necrotizing fasciitis. Despite high serum levels of IgG4, none had evidence of IgG4-related disease. These findings suggest that the increased number of IgG4-positive plasma cells is not the primary etiologic agent in IgG4-related disease. Elevated serum levels of IgG4 is not sufficient to produce the typical disease presentation and should not be considered diagnostic of IgG4-related disease.

Efficacy of thiolated eudragit microspheres as an oral vaccine delivery system to induce mucosal immunity against enterotoxigenic Escherichia coli in mice.

PubMed

Lee, Won-Jung; Cha, Seungbin; Shin, Minkyoung; Jung, Myunghwan; Islam, Mohammad Ariful; Cho, Chong-su; Yoo, Han Sang

2012-05-01

A vaccine delivery system based on thiolated eudragit microsphere (TEMS) was studied in vivo for its ability to elicit mucosal immunity against enterotoxigenic Escherichia coli (ETEC). Groups of mice were orally immunized with F4 or F18 fimbriae of ETEC and F4 or F18 loaded in TEMS. Mice that were orally administered with F4 or F18 loaded TEMS showed higher antigen-specific IgG antibody responses in serum and antigen-specific IgA in saliva and feces than mice that were immunized with antigens only. In addition, oral vaccination of F4 or F18 loaded TEMS resulted in higher numbers of IgG and IgA antigen-specific antibody secreting cells in the spleen, lamina propria, and Peyer's patches of immunized mice than other groups. Moreover, TEMS administration loaded with F4 or F18 induced mixed Th1 and Th2 type responses based on similarly increased levels of IgG1 and IgG2a. These results suggest that F4 or F18 loaded TEMS may be a promising candidate for an oral vaccine delivery system to elicit systemic and mucosal immunity against ETEC. Copyright © 2012 Elsevier B.V. All rights reserved.

Diphtheria toxin IgG levels in military and civilian blood donors in Rio de Janeiro, Brazil.

PubMed

Speranza, F A B; Ishii, S K; Hirata, R; Mattos-Guaraldi, A L; Milagres, L G

2010-01-01

Serologic data on diseases that are preventable by vaccines are necessary to evaluate the success of immunization programs and to identify susceptible subgroups. In the present study, we determined serum IgG levels against diphtheria toxin of military and civilian blood donors (N = 75; 69.3% males and 30.7% females) aged 18-64 years, from the Brazilian Army Biology Institute, Rio de Janeiro, using a commercial diphtheria kit (Diphtheria IgG ELISA; IBL, Germany). Most (63%) unprotected military donors were from the older age group of 41 to 64 years. In contrast, the majority (71%) of young military donors (18 to 30 years) were fully protected. About half of the military donors aged 31 to 40 years were protected against diphtheria. Among the civilians, about 50% of persons aged 18 to 30 years and 31 to 40 years had protective antibody levels against diphtheria as also did 64% of individuals aged 41 to 64 years. All civilians had a similar antibody response (geometric mean = 0.55 IU/mL) independent of age group. Military donors aged 18-30 years had higher IgG levels (geometric mean = 0.82 IU/mL) than military donors of 41-64 years (geometric mean = 0.51 IU/mL; P > 0.05). In conclusion, the existence of a considerable proportion of susceptible adults supports the position that reliable data on the immune status of the population should be maintained routinely and emphasizes the importance of adequate immunization during adulthood.

In utero exposure to Onchocerca volvulus: relationship to subsequent infection intensity and cellular immune responsiveness.

PubMed Central

Elson, L H; Days, A; Calvopiña, M; Paredes, W; Araujo, E; Guderian, R H; Bradley, J E; Nutman, T B

1996-01-01

Afro-Ecuadorian individuals from an area where Onchocerca volvulus is hyperendemic have been monitored for infection over the past 16 years. To determine whether in utero exposure to O. volvulus biases a child's subsequent immune responses, children (9 to 16 years old) for whom the mother's infection status was known were chosen for study. Children of infected mothers (n = 19) had significantly higher levels of skin microfilariae than children of uninfected mothers (n = 13; P = 0.021). While the serum levels of O. volvulus-specific immunoglobulin G (IgG), IgG subclasses, and IgE showed no significant differences between the two groups of children, peripheral blood mononuclear cells of children of infected mothers produced higher levels of Th2-type cytokines to several parasite antigens and lower levels of Th1-type cytokines to nonparasite antigens than those of children of uninfected mothers. Thus, in utero exposure to O. volvulus has a long-term effect on the child's subsequent cellular immune response that may render the child more susceptible to O. volvulus infection postnatally. PMID:8945547

Nasal IgA Provides Protection against Human Influenza Challenge in Volunteers with Low Serum Influenza Antibody Titre.

PubMed

Gould, Victoria M W; Francis, James N; Anderson, Katie J; Georges, Bertrand; Cope, Alethea V; Tregoning, John S

2017-01-01

In spite of there being a number of vaccines, influenza remains a significant global cause of morbidity and mortality. Understanding more about natural and vaccine induced immune protection against influenza infection would help to develop better vaccines. Virus specific IgG is a known correlate of protection, but other factors may help to reduce viral load or disease severity, for example IgA. In the current study we measured influenza specific responses in a controlled human infection model using influenza A/California/2009 (H1N1) as the challenge agent. Volunteers were pre-selected with low haemagglutination inhibition (HAI) titres in order to ensure a higher proportion of infection; this allowed us to explore the role of other immune correlates. In spite of HAI being uniformly low, there were variable levels of H1N1 specific IgG and IgA prior to infection. There was also a range of disease severity in volunteers allowing us to compare whether differences in systemic and local H1N1 specific IgG and IgA prior to infection affected disease outcome. H1N1 specific IgG level before challenge did not correlate with protection, probably due to the pre-screening for individuals with low HAI. However, the length of time infectious virus was recovered from the nose was reduced in patients with higher pre-existing H1N1 influenza specific nasal IgA or serum IgA. Therefore, IgA contributes to protection against influenza and should be targeted in vaccines.

Evaluation of automated assays for immunoglobulin G, M, and A measurements in dog and cat serum.

PubMed

Tvarijonaviciute, Asta; Martínez-Subiela, Silvia; Caldin, Marco; Tecles, Fernando; Ceron, Jose J

2013-09-01

Measurements of immunoglobulins (Igs) in companion animals can be useful to detect deficiencies of the humoral immune system, that can be associated with opportunistic or chronic infections, or other immune-mediated disorders including B-cell neoplasms. The purpose of this study was to evaluate commercially available automated immunoturbidimetric assays designed for human IgG, M, and A measurements in canine and feline serum using species-specific calibrators. Canine and feline serum samples with different IgG, M, and A concentrations were used for the analytical validation of the assays. Intra- and inter-assay precision, linearity under dilution, spiking recovery, and limit of detection were determined. In addition, effects of lipemia, hemolysis, and bilirubinemia were evaluated. Finally, Ig concentrations were determined in small groups of diseased dogs and cats, and compared with healthy groups. Spiking recovery and linearity under dilution tests showed that the assays measured Igs in canine and feline serum samples precisely and accurately. Intra- and inter-assay imprecisions were lower than 15% in all cases. Significantly higher IgG, IgM, and IgA levels were observed in dogs with leishmaniasis, while dogs with pyometra showed a statistically significant increase in IgM and IgA concentrations in comparison with healthy dogs. Significantly higher IgG and IgM levels were observed in FIV-infected cats compared with healthy ones. The automated human Ig assays showed adequate precision and accuracy with serum samples from dogs and cats. Also, they were able to discriminate different concentrations of Igs in healthy and diseased animals. © 2013 American Society for Veterinary Clinical Pathology.

Seroepidemiology of Helicobacter pylori infection in a Mennonite community in Durango State, Mexico.

PubMed

Alvarado-Esquivel, Cosme

2013-06-01

The epidemiology of Helicobacter pylori infection among Mennonites (an ethnic group of German descent living in rural communities in Mexico) has not been previously studied. The prevalence of anti-H. pylori IgG antibodies was examined in 152 Mennonite individuals in Durango State, Mexico, using enzyme-linked immunoassays. Seroprevalence association with sociodemographic, clinical, and behavioral characteristics of the Mennonite community was also investigated. In total, 77 (50.7%) of the 152 Mennonite participants (mean age, 38.4 ± 15.5 years) had H. pylori IgG antibodies, 35 (45.4%) of whom had H. pylori IgG antibody levels higher than 100 U/mL. Males and females had comparable seroprevalence rates of H. pylori and H. pylori IgG antibody levels. On the other hand, seroprevalence of H. pylori increased significantly with age and was significantly higher among women with history of deliveries and abortions than among those with no such obstetric characteristics. Logistic regression analysis of behavioral characteristics showed that H. pylori infection was associated with a low frequency of eating at restaurants and at fast food outlets (up to 10 times/year) (OR = 2.77; 95% CI: 1.28-5.98; p = .009), and eating meat (up to 3 days/week) (OR = 2.84; 95% CI: 1.36-5.91; p = .005). This is the first report on the seroprevalence of H. pylori among Mennonites, factors contributing to such infection, and the association of H. pylori infection with abortions and low frequencies of eating out of home and meat. Further research should be conducted on this topic. © 2013 John Wiley & Sons Ltd.

Comparison of mouse, guinea pig and rabbit models for evaluation of plague subunit vaccine F1+rV270.

PubMed

Qi, Zhizhen; Zhou, Lei; Zhang, Qingwen; Ren, Lingling; Dai, Ruixia; Wu, Benchuan; Wang, Tang; Zhu, Ziwen; Yang, Yonghai; Cui, Baizhong; Wang, Zuyun; Wang, Hu; Qiu, Yefeng; Guo, Zhaobiao; Yang, Ruifu; Wang, Xiaoyi

2010-02-10

In this study, a new subunit vaccine that comprised native F1 and recombinant rV270 was evaluated for protective efficacy using mouse, guinea pig and rabbit models in comparison with the live attenuated vaccine EV76. Complete protection against challenging with 10(6) colony-forming units (CFU) of virulent Yersinia pestis strain 141 was observed for mice immunized with the subunit vaccines and EV76 vaccine. In contrast, the subunit vaccine recipes VII (F1-20 microg+rV270-10 microg) and IX (F1-40 microg+rV270-20 microg) and EV76 vaccine provided 86%, 79% and 93% protection against the same level of challenge in guinea pigs and 100%, 83% and 100% protection in rabbits, respectively. The immunized mice with the vaccines had significantly higher IgG titres than the guinea pigs and rabbits, and the immunized guinea pigs developed significantly higher IgG titres than the rabbits, but the anti-F1 response in guinea pigs was more variable than in the mice and rabbits, indicating that guinea pig is not an ideal model for evaluating protective efficacy of plague subunit vaccine, instead the rabbits could be used as an alternative model. All the immunized animals with EV76 developed a negligible IgG titre to rV270 antigen. Furthermore, analysis of IgG subclasses in the immunized animals showed a strong response for IgG1, whereas those receiving EV76 immunization demonstrated predominant production of IgG1 and IgG2a isotypes. The subunit vaccine and EV76 vaccine are able to provide protection for animals against Y. pestis challenge, but the subunit vaccines have obvious advantages over EV76 in terms of safety of use. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Correlation between antitumor activity of protein A and in vivo formation of defined high molecular weight complexes with immunoglobulin G in BALB/c mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Das, C.; Langone, J.J.

1987-04-15

The purpose of this study was to test the hypothesis that antitumor activity of staphylococcal protein A (SpA) is related to the composition of complexes formed in vivo with IgG. BALB/c mice were inoculated intradermally with 10(6) Meth A fibrosarcoma cells on day 0 and treated i.v. on days 3 and 7 with between 1 and 405 micrograms of SpA. The 45- and 15-micrograms doses significantly inhibited tumor growth and enhanced survival time compared to saline controls in four of four and two of four experiments, respectively. Sucrose gradient ultracentrifugation was used to show that serum from tumor-bearing or normalmore » mice given 45 or 15 micrograms of /sup 125/I-labeled SpA contained only high molecular weight ((IgG)2SpA)2 complexes for up to 24 h after injection, whereas serum from mice given higher ineffective doses (135 and 405 micrograms) contained low molecular weight (IgG)(SpA) complexes over the first 1-4 h. Serum from mice undergoing successful therapy with 45 micrograms of unlabeled SpA also contained only ((IgG)2SpA)2 complexes. In contrast, when mice with large tumors (120-150 mm2) were treated on days 16 and 20, only the 135- and 405-micrograms doses significantly inhibited further tumor growth. Serum from mice with 16-day tumors contained only ((IgG)2SpA)2 complexes even after 5 min and when 135 or 405 micrograms of 125I-SpA was given. This result is consistent with significantly higher levels of total and SpA-reactive IgG in serum from these mice compared to normal mice or mice with 3-day tumors. Our results demonstrate a correlation between antitumor activity of SpA and in vivo formation of ((IgG)2SpA)2 complexes in an established animal model, and help to define the mechanism of SpA action at the molecular level.« less

[Serum immunoglobulin IgG subclass distribution of antibody responses to pertussis toxin and filamentous hemagglutinin of Bordetella pertussis in patients with whooping cough].

PubMed

Rastawicki, Waldemar; Smietańska, Karolina; Rokosz-Chudziak, Natalia; Jagielski, Marek

2013-01-01

The present study was aimed at determining the IgG subclass distribution against pertussis toxin (PT) and filamentous hemagglutinin (FHA) of Bordetella pertussis in patients with whooping cough. The total number of 222 serum samples obtained from patients suspected in clinical investigation for pertussis were tested separately by in-house ELISA for the presence of IgG antibodies to pertussis toxin and filamentous hemagglutinin. The percentage distribution of specific anti-PT and anti-FHA IgG subclass response was calculated only on the basis of group of sera confirmed in the present study as positive for total IgG antibodies (183 sera to PT antigen and 129 to FHA antigen). Paired serum specimens were obtained from 36 patients. Based on the results of determining the level of antibodies in the sera of 40 blood donors, the cut-off limit of serum antibodies for each subclass was set at arithmetic mean plus two standard deviations. Antibodies of IgG1 to pertussis toxin and filamentous hemagglutinin were diagnosed in 151 (82.5%) and 99 (76.7%), IgG2 in 72 (39.0%) and 50 (38.8%), IgG3 in 17 (9.3%) and 43 (33.3%), IgG4 in 55 (30.1%) and 53 (41.1%) serum samples, respectively. There were no significant differences in percentage of sera with IgG1, IgG2 and IgG3 in relation to age of the patients. However, the frequency of occurrence of IgG4 antibodies was highest in the group of the youngest children to the age of 6 years old (61.8% for PT and 68.0% for FHA), and decrease with age, reaching the minimum in the group of patients above 40 years old (13.2% and 4.2% for PT and FHA, respectively). We also found significantly higher frequency of IgG4 to PT and FHA antigens in men than in women. Statistically significant, essential changes in the pattern of IgG subclass during the course of infection were not found. In conclusion, this study showed that all four subclasses of IgG antibodies to pertussis toxin and filamentous hemagglutinin are produced during whooping cough.

A novel antibody engineering strategy for making monovalent bispecific heterodimeric IgG antibodies by electrostatic steering mechanism.

PubMed

Liu, Zhi; Leng, Esther C; Gunasekaran, Kannan; Pentony, Martin; Shen, Min; Howard, Monique; Stoops, Janelle; Manchulenko, Kathy; Razinkov, Vladimir; Liu, Hua; Fanslow, William; Hu, Zhonghua; Sun, Nancy; Hasegawa, Haruki; Clark, Rutilio; Foltz, Ian N; Yan, Wei

2015-03-20

Producing pure and well behaved bispecific antibodies (bsAbs) on a large scale for preclinical and clinical testing is a challenging task. Here, we describe a new strategy for making monovalent bispecific heterodimeric IgG antibodies in mammalian cells. We applied an electrostatic steering mechanism to engineer antibody light chain-heavy chain (LC-HC) interface residues in such a way that each LC strongly favors its cognate HC when two different HCs and two different LCs are co-expressed in the same cell to assemble a functional bispecific antibody. We produced heterodimeric IgGs from transiently and stably transfected mammalian cells. The engineered heterodimeric IgG molecules maintain the overall IgG structure with correct LC-HC pairings, bind to two different antigens with comparable affinity when compared with their parental antibodies, and retain the functionality of parental antibodies in biological assays. In addition, the bispecific heterodimeric IgG derived from anti-HER2 and anti-EGF receptor (EGFR) antibody was shown to induce a higher level of receptor internalization than the combination of two parental antibodies. Mouse xenograft BxPC-3, Panc-1, and Calu-3 human tumor models showed that the heterodimeric IgGs strongly inhibited tumor growth. The described approach can be used to generate tools from two pre-existent antibodies and explore the potential of bispecific antibodies. The asymmetrically engineered Fc variants for antibody-dependent cellular cytotoxicity enhancement could be embedded in monovalent bispecific heterodimeric IgG to make best-in-class therapeutic antibodies. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Herpes virus antibodies seroprevalence in children with autoimmune thyroid disease.

PubMed

Thomas, Dimitrios; Karachaliou, Feneli; Kallergi, Konstantina; Vlachopapadopoulou, Elpis; Antonaki, Georgia; Chatzimarkou, Fotini; Fotinou, Aspasia; Kaldrymides, Philippos; Michalacos, Stefanos

2008-04-01

Elevated titers of antibodies against different herpes virus antigens have been reported in some immunodeficient and systemic autoimmune disorders. To examine if Herpes Simplex Virus (HSV), Epstein-Barr virus (EBV), and cytomegalovirus (CMV) IgG and IgM antibodies are detected more frequently in children with autoimmune thyroid disease (AITD) compared to controls. Thirty-four children with AITD, aged 9.62 +/- 2.35 years, and 31 matched controls, aged 9.24 +/- 2.98 years, were studied. The percentage of EBV IgG+ children with AITD was statistically higher than the percentage of EBV IgG+ controls (82.35% versus 51.61%, P = 0.008). The percentage of EBV IgG+ children with AITD and hypothyroidism was statistically higher than the percentage of EBV IgG+ children with AITD, without hypothyroidism (100% versus 70%, P = 0.024). No other statistically significant differences were observed in HSV-1+2, and CMV IgG or IgM antibodies between the subgroups of children studied. EBV seroprevalence is higher in children with AITD compared to controls and the underlying pathology remains to be elucidated.

Association of immunoglobulin G4 and free light chain with idiopathic pleural effusion.

PubMed

Murata, Y; Aoe, K; Mimura-Kimura, Y; Murakami, T; Oishi, K; Matsumoto, T; Ueoka, H; Matsunaga, K; Yano, M; Mimura, Y

2017-10-01

The cause of pleural effusion remains uncertain in approximately 15% of patients despite exhaustive evaluation. As recently described immunoglobulin (Ig)G4-related disease is a fibroinflammatory disorder that can affect various organs, including the lungs, we investigate whether idiopathic pleural effusion includes IgG4-associated etiology. Between 2000 and 2012, we collected 830 pleural fluid samples and reviewed 35 patients with pleural effusions undiagnosed after pleural biopsy at Yamaguchi-Ube Medical Center. Importantly, IgG4 immunostaining revealed infiltration of IgG4-positive plasma cells in the pleura of 12 patients (34%, IgG4 + group). The median effusion IgG4 level was 41 mg/dl in the IgG4 + group and 27 mg/dl in the IgG4 - group (P < 0·01). The light and heavy chains of effusion IgG4 antibodies of patients in the IgG4 + group were heterogeneous by two-dimensional electrophoresis, indicating the absence of clonality of the IgG4 antibodies. Interestingly, the κ light chains were more heterogeneous than the λ light chains. The measurement of the κ and λ free light chain (FLC) levels in the pleural fluids showed significantly different κ FLC levels (median: 28·0 versus 9·1 mg/dl, P < 0·01) and κ/λ ratios (median: 2·0 versus 1·2, P < 0·001) between the IgG4 + and IgG4 - groups. Furthermore, the κ/λ ratios were correlated with the IgG4 + /IgG + plasma cell ratios in the pleura of the IgG4 + group. Taken together, these results demonstrate the involvement of IgG4 in certain idiopathic pleural effusions and provide insights into the diagnosis, pathogenesis and therapeutic opportunities of IgG4-associated pleural effusion. © 2017 British Society for Immunology.

Differential recognition of P. falciparum VAR2CSA domains by naturally acquired antibodies in pregnant women from a malaria endemic area.

PubMed

Brolin, Kim J M; Persson, Kristina E M; Wahlgren, Mats; Rogerson, Stephen J; Chen, Qijun

2010-02-16

Plasmodium falciparum infected red blood cells (iRBC) express variant surface antigens (VSA) of which VAR2CSA is involved in placental sequestration and causes pregnancy-associated malaria (PAM). Primigravidae are most susceptible to PAM whereas antibodies associated with protection are often present at higher levels in multigravid women. However, HIV co-infection with malaria has been shown to alter this parity-dependent acquisition of immunity, with more severe symptoms as well as more malaria episodes in HIV positive women versus HIV negative women of a similar parity. Using VAR2CSA DBL-domains expressed on the surface of CHO-745 cells we quantified levels of DBL-domain specific IgG in sera from pregnant Malawian women by flow cytometry. Dissociations constants of DBL5epsilon specific antibodies were determined using a surface plasmon resonance technique, as an indication of antibody affinities. VAR2CSA DBL5epsilon was recognized in a gender and parity-dependent manner with anti-DBL5epsilon IgG correlating significantly with IgG levels to VSA-PAM on the iRBC surface. HIV positive women had lower levels of anti-DBL5epsilon IgG than HIV negative women of similar parity. In primigravidae, antibodies in HIV positive women also showed significantly lower affinity to VAR2CSA DBL5epsilon. Pregnant women from a malaria-endemic area had increased levels of anti-DBL5epsilon IgG by parity, indicating this domain of VAR2CSA to be a promising vaccine candidate against PAM. However, it is important to consider co-infection with HIV, as this seems to change the properties of antibody response against malaria. Understanding the characteristics of antibody response against VAR2CSA is undoubtedly imperative in order to design a functional and efficient vaccine against PAM.

Association of serum Clara cell protein CC16 with respiratory infections and immune response to respiratory pathogens in elite athletes.

PubMed

Kurowski, Marcin; Jurczyk, Janusz; Jarzębska, Marzanna; Moskwa, Sylwia; Makowska, Joanna S; Krysztofiak, Hubert; Kowalski, Marek L

2014-04-15

Respiratory epithelium integrity impairment caused by intensive exercise may lead to exercise-induced bronchoconstriction. Clara cell protein (CC16) has anti-inflammatory properties and its serum level reflects changes in epithelium integrity and airway inflammation. This study aimed to investigate serum CC16 in elite athletes and to seek associations of CC16 with asthma or allergy, respiratory tract infections (RTIs) and immune response to respiratory pathogens. The study was performed in 203 Olympic athletes. Control groups comprised 53 healthy subjects and 49 mild allergic asthmatics. Serum levels of CC16 and IgG against respiratory viruses and Mycoplasma pneumoniae were assessed. Allergy questionnaire for athletes was used to determine symptoms and exercise pattern. Current versions of ARIA and GINA guidelines were used when diagnosing allergic rhinitis and asthma, respectively. Asthma was diagnosed in 13.3% athletes, of whom 55.6% had concomitant allergic rhinitis. Allergic rhinitis without asthma was diagnosed in 14.8% of athletes. Mean CC16 concentration was significantly lower in athletes versus healthy controls and mild asthmatics. Athletes reporting frequent RTIs had significantly lower serum CC16 and the risk of frequent RTIs was more than 2-fold higher in athletes with low serum CC16 (defined as equal to or less than 4.99 ng/ml). Athletes had significantly higher anti-adenovirus IgG than healthy controls while only non-atopic athletes had anti-parainfluenza virus IgG significantly lower than controls. In all athletes weak correlation of serum CC16 and anti-parainfluenza virus IgG was present (R = 0.20, p < 0.01). In atopic athletes a weak positive correlations of CC16 with IgG specific for respiratory syncytial virus (R = 0.29, p = 0.009), parainfluenza virus (R = 0.31, p = 0.01) and adenovirus (R = 0.27, p = 0.02) were seen as well. Regular high-load exercise is associated with decrease in serum CC16 levels. Athletes with decreased CC16 are more susceptible to respiratory infections. Atopy may be an additional factor modifying susceptibility to infections in subjects performing regular high-load exercise.

ALTERED IMMUNOGLOBULIN PROFILES IN CHILDREN WITH TOURETTE SYNDROME

PubMed Central

Bos-Veneman, Netty G.P.; Olieman, Renske; Tobiasova, Zuzana; Hoekstra, Pieter J.; Katsovitch, Lily; Bothwell, Alfred L. M.; Leckman, James F.; Kawikova, Ivana

2011-01-01

BACKGROUND Post-infectious autoimmunity and immune deficiency have been implicated in the pathogenesis of Tourette syndrome (TS). We asked here whether B cell immunity of patients with TS differs from healthy subjects. METHODS In two independent cross-sectional samples, we compared serum levels of IgG1, IgG2, IgG3, IgG4, IgM, IgA, and IgE in 21 patients with TS from Yale University (17 males, 4 females, 8–16 years) versus 21 healthy controls (13 males, 8 females, 7–17 years); and in 53 patients with TS from Groningen University (45 males, 8 females, 6–18 years) versus 53 healthy controls (22 males, 31 females, 6–18 years), respectively. We also investigated correlations between Ig concentrations and symptom severity. In 13 additional patients (9 males, 4 females, age range 9–14), we established Ig profiles at time points before, during, and after symptom exacerbations. RESULTS IgG3 levels were significantly lower in Yale patients compared to healthy children (medians 0.28 versus 0.49 mg/ml, p = .04), while levels of IgG2, IgG4, and IgM in patients were lower at trend-level significance (p ≤ .10). Decreased IgG3 (medians 0.45 versus 0.52 mg/ml; p = .05) and IgM (medians 0.30 versus 0.38 mg/ml; p = .04) levels were replicated in the Groningen patients. Ig levels did not correlate with symptom severity. There was a trend-level elevation of IgG1 during symptom exacerbations (p = .09). CONCLUSION These pilot data indicate that at least some patients with TS have decreased serum IgG3, and possibly also IgM levels, though only few subjects had fully expressed Ig immunodeficiency. Whether these changes are related to TS pathogenesis needs to be investigated. PMID:21156204

TLR7 imidazoquinoline ligand 3M-019 is a potent adjuvant for pure protein prototype vaccines.

PubMed

Johnston, Dean; Zaidi, Bushra; Bystryn, Jean-Claude

2007-08-01

Cancer vaccines, while theoretically attractive, present difficult challenges that must be overcome to be effective. Cancer vaccines are often poorly immunogenic and may require augmentation of immunogenicity through the use of adjuvants and/or immune response modifiers. Toll-like receptor (TLR) ligands are a relatively new class of immune response modifiers that may have great potential in inducing and augmenting both cellular and humoral immunity to vaccines. TLR7 ligands produce strong cellular responses and specific IgG2a and IgG2b antibody responses to protein immunogens. This study shows that a new TLR7 ligand, 3M-019, in combination with liposomes produces very strong immune responses to a pure protein prototype vaccine in mice. Female C57BL/6 mice were immunized subcutaneously with ovalbumin (OVA, 0.1 mg/dose) weekly 4x. Some groups were immunized to OVA plus 3M-019 or to OVA plus 3M-019 encapsulated in liposomes. Both antibody and cellular immune responses against OVA were measured after either two or four immunizations. Anti-OVA IgG antibody responses were significantly increased after two immunizations and were substantially higher after four immunizations in mice immunized with OVA combined with 3M-019. Encapsulation in liposomes further augmented antibody responses. IgM responses, on the other hand, were lowered by 3M-019. OVA-specific IgG2a levels were increased 625-fold by 3M-019 in liposomes compared to OVA alone, while anti-OVA IgG2b levels were over 3,000 times higher. In both cases encapsulation of 3M-019 in liposomes was stronger than either liposomes alone or 3M-019 without liposomes. Cellular immune responses were likewise increased by 3M-019 but further enhanced when it was encapsulated in liposomes. The lack of toxicity also indicates that this combination may by safe, effective method to boost immune response to cancer vaccines.

Humans with chronic granulomatous disease maintain humoral immunologic memory despite low frequencies of circulating memory B cells

PubMed Central

Santich, Brian H.; Kim, Jin Young; Posada, Jacqueline G.; Ho, Jason; Buckner, Clarisa M.; Wang, Wei; Kardava, Lela; Garofalo, Mary; Marciano, Beatriz E.; Manischewitz, Jody; King, Lisa R.; Khurana, Surender; Chun, Tae-Wook; Golding, Hana; Fauci, Anthony S.; Malech, Harry L.

2012-01-01

CD27+ memory B cells are reduced in the blood of patients with chronic granulomatous disease (CGD) for reasons and consequences that remain unclear. Here we confirm not only decreased CD27+ but also IgG+ B cells in the blood of CGD patients compared with healthy donors (HDs). However, among IgG+ B cells, the ratio of CD27− to CD27+ was significantly higher in CGD patients compared with HDs. Similar to conventional memory B cells, CD27−IgG+ B cells of CGD patients expressed activation markers and had undergone somatic hypermutation, albeit at levels lower than their CD27+ counterparts. Functional analyses revealed slight reductions in frequencies of total IgG but not influenza-specific memory B-cell responses, as measured by Elispot in CGD patients compared with HDs. Serum IgG levels and influenza-specific antibodies were also normal in these CGD patients. Finally, we provide evidence that influenza-specific memory B cells can be present within the CD27−IgG+ B-cell compartment. Together, these findings show that, despite reduced circulating CD27+ memory B cells, CGD patients maintain an intact humoral immunologic memory, with potential contribution from CD27− B cells. PMID:23074274

[Effects on serum myelin proteins of n-hexane exposure].

PubMed

Yi, Juan; Zhou, Wei; He, Jia-xi; Liu, Qing-jun; Huang, Xian-qing

2011-02-01

Exploring the effects of n-hexane on expression of serum myelin proteins in occupational exposure workers, and finding the early biomarker of n-hexane exposure. In the study, 373 subjects were recruited, 269 exposure workers (work experience of more than1 year) and 104 non-exposure workers were selected. Firstly examined the level of urinary 2,5-hexanedione in the two groups, based on urinary 2,5-hexanedione biological limit value (4 mg/L), the exposed group was divided into high-exposed group and low-exposed group. And then collected blood samples and extracted serum. Human peripheral myelin protein zero (P0) antibody (IgG, IgM) and human peripheral myelin protein two (P2) antibody (IgG, IgM) analysis was performed according to ELISA kit. The concentration of urinary 2,5-hexanedione in the exposed group was (3.10 ± 1.35) mg/L. The level of P0 antibody (IgG, IgM) and P2 antibody (IgG, IgM) in the high-exposed group and low-exposed group were both higher than that in the controls (P < 0.01). P0 antibody and P2 antibody could be used as the early biomarkers of n-hexane exposure, which not only evaluate the occupational hazards in the early, but also provide the policy maker with scientific evidence.

Impact of antibody subclass and disulfide isoform differences on the biological activity of CD200R and βklotho agonist antibodies.

PubMed

Grujic, Ognjen; Stevens, Jennitte; Chou, Robert Y-T; Weiszmann, Jennifer V; Sekirov, Laura; Thomson, Christy; Badh, Anita; Grauer, Stephanie; Chan, Brian; Graham, Kevin; Manchulenko, Kathy; Dillon, Thomas M; Li, Yang; Foltz, Ian N

2017-05-13

Agonism of cell surface receptors by monoclonal antibodies is dependent not only on its ability to bind the target, but also to deliver a biological signal through receptors to the cell. Immunoglobulin G2 antibodies (IgG2s) are made up of a mixture of distinct isoforms (IgG2-A, -B and A/B), which differ by the disulfide connectivity at the hinge region. When evaluating panels of agonistic antibodies against CD200 receptor (CD200R) or βklotho receptor (βklotho), we noticed striking activity differences of IgG1 or IgG2 antibodies with the same variable domains. For the CD200R antibody, the IgG2 antibody demonstrated higher activity than the IgG1 or IgG4 antibody. More significantly, for βklotho, agonist antibodies with higher biological activity as either IgG2 or IgG1 were identified. In both cases, ion exchange chromatography was able to isolate the bioactivity to the IgG2-B isoform from the IgG2 parental mixture. The subclass-related increase in agonist activity was not correlated with antibody aggregation or binding affinity, but was driven by enhanced avidity for the CD200R antibody. These results add to the growing body of evidence that show that conformational differences in the antibody hinge region can have a dramatic impact on the antibody activity and must be considered when screening and engineering therapeutic antibody candidates. The results also demonstrate that the IgG1 (IgG2-A like) or the IgG2-B form may provide the most active form of agonist antibodies for different antibodies and targets. Copyright © 2017 Elsevier Inc. All rights reserved.

Sex-related effects of nutritional supplementation of Escherichia coli: relevance to eating disorders.

PubMed

Tennoune, Naouel; Legrand, Romain; Ouelaa, Wassila; Breton, Jonathan; Lucas, Nicolas; Bole-Feysot, Christine; do Rego, Jean-Claude; Déchelotte, Pierre; Fetissov, Sergueï O

2015-03-01

The biological background of sex-related differences in the development of eating disorders (EDs) is unknown. Recent data showed that gut bacteria Escherichia coli induce autoantibodies against anorexigenic α-melanocyte-stimulating hormone (α-MSH) associated with psychopathology in ED. The aim of this study was to compare the effects of E. coli on feeding and autoantibodies against α-MSH and adrenocorticotropic hormone (ACTH), between female and male rats. Commensal E. coli K12 were given in a culture medium daily to adult Wistar rats by intragastric gavage over a 3-wk period; control rats received culture medium only. Before gavage, E. coli K12 DNA was detected in feces of female but not male rats. E. coli provision was accompanied by an increase in body weight gain in females, but a decrease in body weight gain and food intake in males. Independent of E. coli treatment, plasma levels of anti-α-MSH and ACTH immunoglobulin (Ig)G were higher in female than male rats. Females responded to E. coli by increasing α-MSH IgG levels and affinity, but males by increasing α-MSH IgM levels. Affinity of IgG for ACTH was increased in both E. coli-treated females and males, although with different kinetics. IgG from females stimulated more efficiently α-MSH-induced cyclic adenosine monophosphate production by melanocortin 4 receptor-expressing cells compared with IgG from males. Sex-related response to how E. coli affects feeding and anti-melanocortin hormone antibody production may depend on the presence of these bacteria in the gut before E. coli supplementation. These data suggest that sex-related presence of certain gut bacteria may represent a risk factor for ED development. Copyright © 2015 Elsevier Inc. All rights reserved.

Modulation of the humoral and cellular immune response in Abeta immunotherapy by the adjuvants monophosphoryl lipid A (MPL), cholera toxin B subunit (CTB) and E. coli enterotoxin LT(R192G).

PubMed

Maier, Marcel; Seabrook, Timothy J; Lemere, Cynthia A

2005-10-25

Abeta vaccination or passive transfer of human-specific anti-Abeta antibodies are approaches under investigation to prevent and/or treat Alzheimer's disease (AD). Successful active Abeta vaccination requires a strong and safe adjuvant to induce anti-Abeta antibody formation. We compared the adjuvants monophosphoryl lipid A (MPL)/trehalose dicorynomycolate (TDM), cholera toxin B subunit (CTB) and Escherichia coli heat-labile enterotoxin LT(R192G) for their ability to induce a humoral and cellular immune reaction, using fibrillar Abeta1-40/42 as a common immunogen in wildtype B6D2F1 mice. Subcutaneous (s.c.) administration with MPL/TDM resulted in anti-Abeta antibodies levels up to four times higher compared to s.c. LT(R192G). Using MPL/TDM, the anti-Abeta antibodies induced were mainly IgG2b, IgG1 and lower levels of IgG2a and IgM, with a moderate splenocyte proliferation and IFN-gamma production in vitro upon stimulation with Abeta1-40/42. LT(R192G), previously shown by us to induce robust titers of anti-Abeta antibodies, generated predominantly IgG2b and IgG1 anti-Abeta antibodies with very low splenocyte proliferation and IFN-gamma production. Weekly intranasal (i.n.) administration over 11 weeks of Abeta40/42 with CTB induced only moderate levels of antibodies. All immunogens generated antibodies that recognized mainly the Abeta1-7 epitope and specifically detected amyloid plaques on AD brain sections. In conclusion, MPL/TDM, in addition to LT(R192G), is an effective adjuvant when combined with Abeta40/42 and may aid in the design of Abeta immunotherapy.

Detection of IgE, IgG, IgA and IgM antibodies against raw and processed food antigens

PubMed Central

Vojdani, Aristo

2009-01-01

Background Despite the first documented case of food allergy to cooked food in 1921 by Prausnitz and Kustner, all commercial food antigens are prepared from raw food. Furthermore, all IgE and IgG antibodies against dietary proteins offered by many clinical laboratories are measured against raw food antigens. Methods We developed an enzyme-linked immunosorbent assay for the measurement of IgE, IgG, IgA and IgM antibodies against raw and processed food antigens. Sera with low or high reactivity to modified food antigens were subjected to myelin basic protein, oxidized low density lipoprotein, and advanced glycation end products (AGE) such as AGE-human serum albumin and AGE-hemoglobin. Results Compared to raw food antigens, IgE antibodies showed a 3–8-fold increase against processed food antigens in 31% of the patients. Similarly, IgG, IgA and IgM antibodies against modified food antigens overall were found at much higher levels than antibody reactions against raw food antigens. Almost every tested serum with high levels of antibodies against modified food antigens showed very high levels of antibodies against myelin basic protein, oxidized low density lipoprotein, AGE-human serum albumin and AGE-hemoglobin. Conclusion We conclude that the determination of food allergy, intolerance and sensitivity would be improved by testing IgE, IgG, IgA and IgM antibodies against both raw and processed food antigens. Antibodies against modified food antigens, by reacting with AGEs and tissue proteins, may cause perturbation in degenerative and autoimmune diseases such as diabetes, atherosclerosis, inflammation, autoimmunity, neurodegeneration and neuroautoimmunity. PMID:19435515

Functionalized hollow fiber membrane cartridge for adsorption of Anticofactor/Antiphospholipid antibodies: a potential tool for treatment.

PubMed

Darnige, L; Legallais, C; Arvieux, J; Pitiot, O; Vijayalakshmi, M A

1999-09-01

It is of considerable interest to ascertain whether a hollow fiber cartridge containing histidine immobilized on polyethylenevinyl alcohol membrane (His-PEVA) is able to retain specific autoantibodies involved in antiphospholipid syndrome. To this end diluted patient pathogenic plasma containing high levels of anti-beta2-glycoprotein I (anti-beta2GPI) and antiprothrombin antibodies was processed through the functionalized cartridge. The adsorbed material was then eluted under mild conditions and analyzed; an enrichment of the eluted fractions in total IgG and more specifically in IgG2 subclass was observed, compared with the injected sample. Enzyme-linked immunosorbent assay tests showed a higher specific binding of antiprothrombin and anti-beta2GPI in these fractions. This was in accordance with the concomitant higher anticoagulant activity measured on the same fractions. All in vitro results clearly demonstrated the ability of the His-PEVA cartridge to preferentially adsorb these autoantibodies. Hence the functionalized cartridge represents a potential tool for the treatment of antiphospholipid syndrome by selective extracorporeal removal of IgG.

TIM-1 signaling in B cells regulates antibody production

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma, Juan; Usui, Yoshihiko; Department of Ophthalmology, Tokyo Medical University, 6-7-1 Nishi-shinjuku-ku, Tokyo 160-0023

Highlights: {yields} TIM-1 is highly expressed on anti-IgM + anti-CD40-stimulated B cells. {yields} Anti-TIM-1 mAb enhanced proliferation and Ig production on activated B cell in vitro. {yields} TIM-1 signaling regulates Ab production by response to TI-2 and TD antigens in vivo. -- Abstract: Members of the T cell Ig and mucin (TIM) family have recently been implicated in the control of T cell-mediated immune responses. In this study, we found TIM-1 expression on anti-IgM- or anti-CD40-stimulated splenic B cells, which was further up-regulated by the combination of anti-IgM and anti-CD40 Abs. On the other hand, TIM-1 ligand was constitutively expressedmore » on B cells and inducible on anti-CD3{sup +} anti-CD28-stimulated CD4{sup +} T cells. In vitro stimulation of activated B cells by anti-TIM-1 mAb enhanced proliferation and expression of a plasma cell marker syndecan-1 (CD138). We further examined the effect of TIM-1 signaling on antibody production in vitro and in vivo. Higher levels of IgG2b and IgG3 secretion were detected in the culture supernatants of the anti-TIM-1-stimulated B cells as compared with the control IgG-stimulated B cells. When immunized with T-independent antigen TNP-Ficoll, TNP-specific IgG1, IgG2b, and IgG3 Abs were slightly increased in the anti-TIM-1-treated mice. When immunized with T-dependent antigen OVA, serum levels of OVA-specific IgG2b, IgG3, and IgE Abs were significantly increased in the anti-TIM-1-treated mice as compared with the control IgG-treated mice. These results suggest that TIM-1 signaling in B cells augments antibody production by enhancing B cell proliferation and differentiation.« less

Treatment response in Kawasaki disease is associated with sialylation levels of endogenous but not therapeutic intravenous immunoglobulin G.

PubMed

Ogata, Shohei; Shimizu, Chisato; Franco, Alessandra; Touma, Ranim; Kanegaye, John T; Choudhury, Biswa P; Naidu, Natasha N; Kanda, Yutaka; Hoang, Long T; Hibberd, Martin L; Tremoulet, Adriana H; Varki, Ajit; Burns, Jane C

2013-01-01

Although intravenous immunoglobulin (IVIG) is highly effective in Kawasaki disease (KD), mechanisms are not understood and 10-20% of patients are treatment-resistant, manifesting a higher rate of coronary artery aneurysms. Murine models suggest that α2-6-linked sialic acid (α2-6Sia) content of IVIG is critical for suppressing inflammation. However, pro-inflammatory states also up-regulate endogenous levels of β-galactoside:α2-6 sialyltransferase-I (ST6Gal-I), the enzyme that catalyzes addition of α2-6Sias to N-glycans. We asked whether IVIG failures correlated with levels of α2-6Sia on infused IVIG or on the patient's own endogenous IgG. We quantified levels of α2-6Sia in infused IVIG and endogenous IgG from 10 IVIG-responsive and 10 resistant KD subjects using multiple approaches. Transcript levels of ST6GAL1, in patient whole blood and B cell lines were evaluated by RT-PCR. Plasma soluble (s)ST6Gal-I levels were measured by ELISA. There was no consistent difference in median sialylation levels of infused IVIG between groups. However, α2-6Sia levels in endogenous IgG, ST6GAL1 transcript levels, and ST6Gal-I protein in serum from IVIG-resistant KD subjects were lower than in responsive subjects at both pre-treatment and one-year time points (p <0.001, respectively). Our data indicate sialylation levels of therapeutic IVIG are unrelated to treatment response in KD. Rather, lower sialylation of endogenous IgG and lower blood levels of ST6GALI mRNA and ST6Gal-I enzyme predict therapy resistance. These differences were stable over time, suggesting a genetic basis. Because IVIG-resistance increases risk of coronary artery aneurysms, our findings have important implications for the identification and treatment of such individuals.

Treatment Response in Kawasaki Disease Is Associated with Sialylation Levels of Endogenous but Not Therapeutic Intravenous Immunoglobulin G

PubMed Central

Ogata, Shohei; Shimizu, Chisato; Franco, Alessandra; Touma, Ranim; Kanegaye, John T.; Choudhury, Biswa P.; Naidu, Natasha N.; Kanda, Yutaka; Hoang, Long T.; Hibberd, Martin L.; Tremoulet, Adriana H.; Varki, Ajit; Burns, Jane C.

2013-01-01

Objectives Although intravenous immunoglobulin (IVIG) is highly effective in Kawasaki disease (KD), mechanisms are not understood and 10-20% of patients are treatment-resistant, manifesting a higher rate of coronary artery aneurysms. Murine models suggest that α2-6-linked sialic acid (α2-6Sia) content of IVIG is critical for suppressing inflammation. However, pro-inflammatory states also up-regulate endogenous levels of β-galactoside:α2-6 sialyltransferase-I (ST6Gal-I), the enzyme that catalyzes addition of α2-6Sias to N-glycans. We asked whether IVIG failures correlated with levels of α2-6Sia on infused IVIG or on the patient’s own endogenous IgG. Methods We quantified levels of α2-6Sia in infused IVIG and endogenous IgG from 10 IVIG-responsive and 10 resistant KD subjects using multiple approaches. Transcript levels of ST6GAL1, in patient whole blood and B cell lines were evaluated by RT-PCR. Plasma soluble (s)ST6Gal-I levels were measured by ELISA. Results There was no consistent difference in median sialylation levels of infused IVIG between groups. However, α2-6Sia levels in endogenous IgG, ST6GAL1 transcript levels, and ST6Gal-I protein in serum from IVIG-resistant KD subjects were lower than in responsive subjects at both pre-treatment and one-year time points (p <0.001, respectively). Conclusions Our data indicate sialylation levels of therapeutic IVIG are unrelated to treatment response in KD. Rather, lower sialylation of endogenous IgG and lower blood levels of ST6GALI mRNA and ST6Gal-I enzyme predict therapy resistance. These differences were stable over time, suggesting a genetic basis. Because IVIG-resistance increases risk of coronary artery aneurysms, our findings have important implications for the identification and treatment of such individuals. PMID:24324693

High seroprevalence of Toxoplasma gondii infection in a subset of Mexican patients with work accidents and low socioeconomic status.

PubMed

Alvarado-Esquivel, Cosme; Torres-Castorena, Alejandro; Liesenfeld, Oliver; Estrada-Martínez, Sergio; Urbina-Álvarez, Jesús D

2012-01-11

Toxoplasma gondii has been associated with reflex impairment and traffic accidents. It is unknown whether Toxoplasma infection might be associated with work accidents. Therefore, using a case-control seroprevalence study design, 133 patients with a recent work accident and 266 control subjects of the general population from the same region were examined with enzyme-linked immunoassays for the presence and levels of anti-Toxoplasma IgG antibodies and anti-Toxoplasma IgM antibodies. Socio-demographic, work, clinical and behavioral characteristics from each worker were obtained. Eleven (8.3%) of 133 patients, and 14 (5.3%) of 266 controls had anti-T. gondii IgG antibodies. Anti-T. gondii IgG levels were higher than 150 IU/ml in 8 (6%) patients and 10 (3.8%) controls. Anti-T. gondii IgM antibodies were found in one (0.8%) of the workers, and in 6 (2.3%) of the controls. No statistically significant differences in the IgG seroprevalences, frequencies of high IgG levels, and IgM seroprevalences among patients and controls were found. In contrast, a low socio-economic level in patients with work accidents was associated with Toxoplasma seropositivity (P = 0.01). Patients with work accidents and low socioeconomic status showed a significantly (OR = 3.38; 95% CI: 0.84-16.06; P = 0.04) higher seroprevalence of T. gondii infection than controls of the same socioeconomic status (15.1% vs. 5%, respectively). Multivariate analysis showed a positive association of T. gondii infection with boar meat consumption (OR = 3.04; 95% CI: 1.03-8.94; P = 0.04). In contrast, a negative association between T. gondii infection and national trips (OR = 0.40; 95% CI: 0.17-0.96; P = 0.04), sausage consumption (OR = 0.20; 95% CI: 0.05-0.68; P = 0.01), and ham consumption (OR = 0.16; 95% CI: 0.05-0.51; P = 0.002) was found. In the study described here seropositivity to T. gondii was associated to work accidents in a subset of patients with low socioeconomic status. This is the first report of an association of T. gondii infection and work accidents. Further studies to confirm our results are needed. Results may help in designing optimal prevention strategies to avoid T. gondii infection.

MuSK induced experimental autoimmune myasthenia gravis does not require IgG1 antibody to MuSK.

PubMed

Küçükerden, Melike; Huda, Ruksana; Tüzün, Erdem; Yılmaz, Abdullah; Skriapa, Lamprini; Trakas, Nikos; Strait, Richard T; Finkelman, Fred D; Kabadayı, Sevil; Zisimopoulou, Paraskevi; Tzartos, Socrates; Christadoss, Premkumar

2016-06-15

Sera of myasthenia gravis (MG) patients with muscle-specific receptor kinase-antibody (MuSK-Ab) predominantly display the non-complement fixing IgG4 isotype. Similarly, mouse IgG1, which is the analog of human IgG4, is the predominant isotype in mice with experimental autoimmune myasthenia gravis (EAMG) induced by MuSK immunization. The present study was performed to determine whether IgG1 anti-MuSK antibody is required for immunized mice to develop EAMG. Results demonstrated a significant correlation between clinical severity of EAMG and levels of MuSK-binding IgG1+, IgG2+ and IgG3+ peripheral blood B cells in MuSK-immunized wild-type (WT) mice. Moreover, MuSK-immunized IgG1 knockout (KO) and WT mice showed similar EAMG severity, serum MuSK-Ab levels, muscle acetylcholine receptor concentrations, neuromuscular junction immunoglobulin and complement deposit ratios. IgG1 and IgG3 were the predominant anti-MuSK isotypes in WT and IgG1 KO mice, respectively. These observations demonstrate that non-IgG1 isotypes can mediate MuSK-EAMG pathogenesis. Copyright © 2016 Elsevier B.V. All rights reserved.

The relationship of the p–k titre to the serum ige level in patients with leprosy

PubMed Central

Hamburger, R. N.; Fernandez-Cruz, E.; Arnaiz, A.; Perez, B.; Bootello, A.

1974-01-01

Fifty patients with leprosy were found to have P–K titres inversely related to their serum IgE levels. Patients with leprosy react in a manner similar to normal individuals and to patients with other diseases. Serum IgG, IgM, IgA and complement were measured in twenty-five of the leprosy patients in addition to the serum IgE and only the IgG significantly positively correlated with the serum IgE. All of these leprosy patients were shown to react to exogenous histamine and they released endogenous histamine when chemically stimulated. Two patients had absent flare responses with normal weals, the remaining forty-eight had complete weal and flare responses. Higher serum IgE levels were noted in those patients with recent institution of chemotherapy. PMID:4143279

Levels of salivary immunoglobulins and periodontal evaluation in smoking patients.

PubMed

Giuca, Maria Rita; Pasini, Marco; Tecco, Simona; Giuca, Giacomo; Marzo, Giuseppe

2014-02-06

The aim of this study was to assess the level of salivary immunoglobulins and periodontal status in smokers and non-smokers. Unstimulated saliva of 30 subjects (mean age 24.2 ± 3.5 years) who were smokers (test group) and of 30 subjects (mean age 25.3 ± 3.8 years) who were non-smokers (control group) was collected and centrifugated; IgA, IgG, and IgM were measured with the colorimetric immunoenzymatic method. Moreover, the following periodontal clinical parameters were recorded for each subject: plaque index (PI), gingival index (GI), probing depth (PD), and clinical attachment level (CAL). A significantly (p< 0.05) lower Ig level was observed in smoking patients (IgA: 20.0 ± 1.2 mg/dl; IgM: 19.5 ± 1.6 mg/dl; IgG: 8.1 ± 1.4 mg/dl) compared to levels in the non-smoking control group (IgA: 234.1 ± 65.2 mg/dl; IgM: 121.0 ± 31.7 mg/dl; IgG: 1049.4 ± 102 mg/dl). In the test group, PI (2.2 ± 0.3), GI (2.4 ± 0.5), PD (49.3 ± 9.2%), and CAL (49.3 ± 4.6%) were higher (p< 0.05) than those observed in the control group (PI: 0.8 ± 0.4; GI: 0.7 ± 0.3; PD: 10.6 ± 2.4%; CAL: 3.1 ± 0.8%). Smoking subjects showed lower levels of salivary IgA, IgG, and IgM and a worse periodontal condition than non-smoking subjects. On the base of our study, as smoking subjects also had lower levels of IgA, IgG, and IgM in their saliva than non-smoking subjects, despite the fact that there is little evidence that the salivary Igs have a protective action against periodontitis and that the whole saliva does not result in whole from the salivary glands, it can be concluded that the deteriorated periodontal health conditions of these patients can be attributed in part to a lowering of the host's defense due to a decrease in the quantity of Igs in salivary fluid.

OVA-bound nanoparticles induce OVA-specific IgG1, IgG2a, and IgG2b responses with low IgE synthesis.

PubMed

Yanase, Noriko; Toyota, Hiroko; Hata, Kikumi; Yagyu, Seina; Seki, Takahiro; Harada, Mitsunori; Kato, Yasuki; Mizuguchi, Junichiro

2014-10-14

There is an urgent requirement for a novel vaccine that can stimulate immune responses without unwanted toxicity, including IgE elevation. We examined whether antigen ovalbumin (OVA) conjugated to the surface of nanoparticles (NPs) (OVA-NPs) with average diameter of 110nm would serve as an immune adjuvant. When BALB/c mice were immunized with OVA-NPs, they developed sufficient levels of OVA-specific IgG1 antibody responses with low levels of IgE synthesis, representing helper T (Th)2-mediated humoral immunity. OVA-specific IgG2a and IgG2b responses (i.e., Th1-mediated immunity) were also induced by secondary immunization with OVA-NPs. As expected, immunization with OVA in alum (OVA-alum) stimulated humoral immune responses, including IgG1 and IgE antibodies, with only low levels of IgG2a/IgG2b antibodies. CD4-positive T cells from mice primed with OVA-NPs produced substantial levels of IL-21 and IL-4, comparable to those from OVA-alum group. The irradiated mice receiving OVA-NPs-primed B cells together with OVA-alum-primed T cells exhibited enhanced anti-OVA IgG2b responses relative to OVA-alum-primed B cells and T cells following stimulation with OVA-NPs. Moreover, when OVA-NPs-primed, but not OVA-alum-primed, B cells were cultured in the presence of anti-CD40 monoclonal antibody, IL-4, and IL-21, or LPS plus TGF-β in vitro, OVA-specific IgG1 or IgG2b antibody responses were elicited, suggesting that immunization with OVA-NPs modulates B cells to generate IgG1 and IgG2b responses. Thus, OVA-NPs might exert their adjuvant action on B cells, and they represent a promising potential vaccine for generating both IgG1 and IgG2a/IgG2b antibody responses with low IgE synthesis. Copyright © 2014 Elsevier Ltd. All rights reserved.

Anti-Plasmodium falciparum invasion ligand antibodies in a low malaria transmission region, Loreto, Peru

PubMed Central

2012-01-01

Background Erythrocyte invasion by Plasmodium falciparum is a complex process that involves two families; Erythrocyte Binding-Like (EBL) and the Reticulocyte Binding-Like (PfRh) proteins. Antibodies that inhibit merozoite attachment and invasion are believed to be important in mediating naturally acquired immunity and immunity generated by parasite blood stage vaccine candidates. The hypotheses tested in this study were 1) that antibody responses against specific P. falciparum invasion ligands (EBL and PfRh) differ between symptomatic and asymptomatic individuals living in the low-transmission region of the Peruvian Amazon and 2), such antibody responses might have an association, either direct or indirect, with clinical immunity observed in asymptomatically parasitaemic individuals. Methods ELISA was used to assess antibody responses (IgG, IgG1 and IgG3) against recombinant P. falciparum invasion ligands of the EBL (EBA-175, EBA-181, EBA-140) and PfRh families (PfRh1, PfRh2a, PfRh2b, PfRh4 and PfRh5) in 45 individuals infected with P. falciparum from Peruvian Amazon. Individuals were classified as having symptomatic malaria (N=37) or asymptomatic infection (N=8). Results Antibody responses against both EBL and PfRh family proteins were significantly higher in asymptomatic compared to symptomatic individuals, demonstrating an association with clinical immunity. Significant differences in the total IgG responses were observed with EBA-175, EBA-181, PfRh2b, and MSP119 (as a control). IgG1 responses against EBA-181, PfRh2a and PfRh2b were significantly higher in the asymptomatic individuals. Total IgG antibody responses against PfRh1, PfRh2a, PfRh2b, PfRh5, EBA-175, EBA-181 and MSP119 proteins were negatively correlated with level of parasitaemia. IgG1 responses against EBA-181, PfRh2a and PfRh2b and IgG3 response for PfRh2a were also negatively correlated with parasitaemia. Conclusions These data suggest that falciparum malaria patients who develop clinical immunity (asymptomatic parasitaemia) in a low transmission setting such as the Peruvian Amazon have antibody responses to defined P. falciparum invasion ligand proteins higher than those found in symptomatic (non-immune) patients. While these findings will have to be confirmed by larger studies, these results are consistent with a potential role for one or more of these invasion ligands as a component of an anti-P. falciparum vaccine in low-transmission malaria-endemic regions. PMID:23110555

Levels of sVCAM-1 and sICAM-1 in patients with lyme disease.

PubMed

Biesiada, Grazyna; Czepiel, Jacek; Sobczyk-Krupiarz, Iwona; Salamon, Dominika; Garlicki, Aleksander; Mach, Tomasz

2009-04-01

Lyme disease is a multi-organ animal-borne disease caused by the spirochete Borrelia burgdorferi (Bb). As the pathogenesis of Lyme borreliosis is not fully understood, the study has been designed to examine levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1) in serum and the cerebrospinal fluid (CSF) of patients with Lyme borreliosis and their associations with clinical signs and symptoms and anti-Borrelia burgdorferi (anti-Bb) antibody titers. Sixty-four patients were enrolled in the study, including 39 patients treated for Lyme borreliosis and 25 without the disease (control group). In both groups sVCAM-1 and sICAM-1 levels were determined in serum and the CSF. Mean serum sICAM-1 and sVCAM-1 levels were higher in patients with Lyme borreliosis than in the control group. Serum sICAM-1 levels were significantly lower among patients with results positive for immunoglobulin M seroreactivity with Bb than among those with negative antibody responses. In patients with Bb-specific serum immunoglobulin G (IgG) antibodies, significantly higher serum sICAM-1 levels were found. Higher sVCAM-1 and sICAM-1 levels in the CSF were observed in patients positive for anti-Bb IgG antibody titers in the CSF. In patients with Lyme borreliosis, endothelial cell activation results in elevated levels of sICAM-1 and sVCAM-1 in serum and the CSF.

Hyperreactive malarial splenomegaly is associated with low levels of antibodies against red blood cell and Plasmodium falciparum derived glycolipids in Yanomami Amerindians from Venezuela.

PubMed

Vivas, Livia; O'Dea, Kieran P; Noya, Oscar; Pabon, Rosalba; Magris, Magda; Botto, Carlos; Holder, Anthony A; Brown, K Neil

2008-03-01

The immunological basis of the aberrant immune response in hyperreactive malarial splenomegaly (HMS) is poorly understood, but believed to be associated with polyclonal B cell activation by an unidentified malaria mitogen, leading to unregulated immunoglobulin and autoantibody production. HMS has been previously reported in Yanomami communities in the Upper Orinoco region of the Venezuelan Amazon. To investigate a possible association between antibody responses against Plasmodium falciparum and uninfected red blood cell (URBC) glycolipids and splenomegaly, a direct comparison of the parasite versus host anti-glycolipid antibody responses was made in an isolated community of this area. The anti-P. falciparum glycolipid (Pfglp) response was IgG3 dominated, whereas the uninfected red blood cell glycolipid (URBCglp) response showed a predominance of IgG1. The levels of IgG1 against Pfglp, and of IgG4 and IgM against URBCglp were significantly higher in women, while the anti-Pfglp or URBCglp IgM levels were inversely correlated with the degree of splenomegaly. Overall, these results suggest differential regulation of anti-parasite and autoreactive responses and that these responses may be linked to the development and evolution of HMS in this population exposed to endemic malaria. The high mortality rates associated with HMS point out that its early diagnosis together with the implementation of malaria control measures in these isolated Amerindian communities are a priority.

Cytomegalovirus neutralization by hyperimmune and standard intravenous immunoglobulin preparations.

PubMed

Planitzer, Christina B; Saemann, Marcus D; Gajek, Hartwig; Farcet, Maria R; Kreil, Thomas R

2011-08-15

Cytomegalovirus (CMV) remains one of the most important pathogens after transplantation, potentially leading to CMV disease, allograft dysfunction, acute, and chronic rejection and opportunistic infections. Immunoglobulin G (IgG) preparations with high antibody titers against CMV are a valuable adjunctive prevention and treatment option for clinicians and apart from standard intravenous immunoglobulin (IVIG), CMV hyperimmune preparations are available. The CMV antibody titer of these preparations is typically determined by Enzyme-linked immunosorbent assay (ELISA), also used for the selection of high titer plasma donors for the production of the CMV Hyperimmune product. However, CMV ELISA titers do not necessarily correlate with CMV antibody function which is determined by virus neutralization tests. CMV antibody titers were determined by both ELISA and virus neutralization assay and the IgG subclass distribution was compared between a CMV hyperimmune licensed in Europe and standard IVIG preparations. Although the expected high CMV IgG ELISA antibody titers were confirmed for three lots of a CMV hyperimmune preparation, the functionally more relevant CMV neutralizing antibody titers were significantly higher for 31 lots of standard IVIG preparations. Moreover, considerably lower IgG3 levels were found for the CMV hyperimmune preparation compared with standard IVIG preparations. The higher functional CMV neutralization titers of standard IVIG preparations and the better availability of these preparations, suggest that these products could be a valuable alternative to the CMV hyperimmune preparation.

[Severe asthmatic crisis during general anesthesia in a patient with IgG4 related disease].

PubMed

Moriya, Machika; Oda, Shinya; Nakane, Masaki; Kawamae, Kaneyuki

2014-04-01

We experienced severe asthmatic crisis during general anesthesia in a 45-year-old man with IgG4-related disease, COPD and athma undergoing removal of submandibular gland. The ventilatiory failure was caused by the stimulation of the operation, sputum, and neostigmine. His serum IgG4 level was extremely high. IgG4 related disease is a recently emerging entity characterized by a diffuse or mass forming inflammatory reaction rich in IgG4-positive plasma cells associated with fibrosclerosis and obliterative phlebitis. It is associated with an elevated serum level of IgG4 and an allergic disease. We must be careful in perioperative management of the patients with IgG4-related disease because general anesthesia can induce asthmatic crisis.

[Immunological status of the pediatric patient who has undergone heart surgery].

PubMed

Valenzuela Flores, A; Wakida, G; Limón Rojas, A; Obregón, C; Orihuela, O; Romero, C

1995-01-01

Communication of results a study the effect of open and closed-heart surgery in the immune system of infants and children. Data collected 24 hrs before anesthesia and surgery and five days after surgery. Operating room and pediatric intensive care of Hospital Central de Petróleos Mexicanos (PEMEX) in the South, Mexico City. Children undergoing surgery for correction of congenital heart disease (age 16 months to 14 years). A total of 16 patients. increased neutrophil counts with luymphopenia in both groups (p < 0.05), serum levels of the complement components C3 and C4 were higher after surgery, serum immunoglobulin IgG, IgA and IgM were higher after surgery, serum immunoglobulin IgG, IgA and IgM were decreased form preoperative levels (p < 0.01). Two patients had infection in the surgical wound. The effect of open and closed-heart surgery produced transitory immunodeficiency with recuperation of his immune systems and 5th day after surgery.

Development of chitosan-pullulan composite nanoparticles for nasal delivery of vaccines: in vivo studies.

PubMed

Cevher, Erdal; Salomon, Stefan K; Somavarapu, Satyanarayana; Brocchini, Steve; Alpar, H Oya

2015-01-01

Here, we aimed at developing chitosan/pullulan composite nanoparticles and testing their potential as novel systems for the nasal delivery of diphtheria toxoid (DT). All the chitosan derivatives [N-trimethyl (TMC), chloride and glutamate] and carboxymethyl pullulan (CMP) were synthesised and antigen-loaded composites were prepared by polyion complexation of chitosan and pullulan derivatives (particle size: 239-405 nm; surface charge: +18 and +27 mV). Their immunological effects after intranasal administration to mice were compared to intramuscular route. Composite nanoparticles induced higher levels of IgG responses than particles formed with chitosan derivative and antigen. Nasally administered TMC-pullulan composites showed higher DT serum IgG titre when compared with the other composites. Co-encapsulation of CpG ODN within TMC-CMP-DT nanoparticles resulted in a balanced Th1/Th2 response. TMC/pullulan composite nanoparticles also induced highest cytokine levels compared to those of chitosan salts. These findings demonstrated that TMC-CMP-DT composite nanoparticles are promising delivery system for nasal vaccination.

[Blood serum levels of immunoglobulins among African children: Seasonal variations and ethnic factors (a study done in Lourenco-Marques among a group of 11-year olds) (author's transl)].

PubMed

Martins, D; Levy, F M; Cabau, N

1975-06-20

The blood titers of IgG, IgA and IgM and total proteins were determined in October 1971 (dry season) and again in April 1972 (wet season) among girls and boys belonging to 4 ethnic groups: White, Bantu, Indian, Mixed. Parasitic studies were also done. These studies indicate a rise of IgM among the girls and of IgA in both sexes from October 1971 to April 1972. The average IgM titer among the four groups is higher than the one found in the Occident. This is especially notable for the Bantu and the Mixed. The Indian levels exceeded, on the average, the White group's. The average IgG figures are only slightly higher than those found in the literature for Western populations. Genetic influences do not appear to explain the differences found between the ethnic groups. The role of environment is stressed, and parasitic influences are discussed.

Gastrointestinal sensitivity to soy and milk proteins in patients with IgA nephropathy.

PubMed

Kloster Smerud, H; Fellström, B; Hällgren, R; Osagie, S; Venge, P; Kristjánsson, G

2010-11-01

sensitivity to food antigens has been postulated as a contributing factor to the pathogenesis of IgA nephropathy (IgAN). in this study we used a recently developed mucosal patch technique to evaluate rectal mucosal sensitivity to soy and cow's milk (CM) proteins in IgAN patients (n = 28) compared to healthy subjects (n = 18). The rectal mucosal production of nitric oxide (NO) and release of myeloperoxidase (MPO) and eosinophil cationic protein (ECP) were measured. Serum samples were analyzed for IgA and IgG antibodies to alpha-lactalbumin, beta-lactoglobulin, casein and soy. 14 of 28 (14/28) patients experienced a rectal mucosal reaction, measured by increased NO and/or MPO levels, upon rectal challenge with soy and/or cow's milk proteins. The levels of IgG antibodies to alpha-lactalbumin, beta-lactoglobulin and casein were significantly higher in CM sensitive as compared with non-sensitive IgAN patients, whereas the mean serum levels of IgA antibodies were similar. No differences were seen in serum levels of IgA or IgG antibodies to soy. it is concluded that approximately half of our IgAN patients have a rectal mucosal sensitivity to soy or CM, and that an immune reactivity against antigens may be involved in the pathogenesis of IgAN in this subgroup of patients.

Immune response in the hamster: definition of a novel IgG not expressed in all hamster strains.

PubMed Central

Coe, J E; Schell, R F; Ross, M J

1995-01-01

A new IgG isotype is described in serum from Syrian hamsters. This 7S-IgG is called IgG3 and was isolated from IgG1 and IgG2 because of its great affinity for protein A. The unique antigenic determinants of IgG3 were identified with a specific rabbit antisera. IgG3 is the least expressed IgG subclass in Syrian hamsters, but serum levels increase more than 10-fold after immunization or infection. Although found in all tested outbred strains, IgG3 is expressed in only some of the commercially available inbred strains of Syrian hamsters. Five inbred hamster strains were examined, and in three strains (CB, LHC and MHA) IgG3 was not detected in normal serum or in immune serum, indicating serum levels at least 100-fold less than other normal inbred/outbred hamsters. The results of breeding experiments suggests a single gene defect is responsible for this non-expression of IgG3. Immunodeficiency was not associated with this IgG3 deficiency. Selective deficiencies of immunoglobulin classes/subclasses in experimental animals are rare. The evolution of a similar IgG3 deficiency in these three hamster strains during inbreeding suggests a novel and efficient mechanism for regulation of IgG3 synthesis in the Syrian hamster. Images Figure 2 Figure 3 Figure 5 PMID:7590875

A toddler PCV booster dose following 3 infancy priming doses increases circulating serotype-specific IGG levels but does not increase protection against carriage.

PubMed

Dagan, Ron; Ben-Shimol, Shalom; Simell, Birgit; Greenberg, David; Porat, Nurith; Käyhty, Helena; Givon-Lavi, Noga

2018-05-11

We compared PCV7 serological response and protection against carriage in infants receiving 3 doses (2, 4, 6 months; 3+0 schedule) to those receiving a booster (12 months; 3+1). A prospective, randomized controlled study, conducted between 2005 and 2008, before PCVs were implemented in Israel. Healthy infants were randomized 1:1:1 to receive 3+1, 3+0 and 0+2 (control group; 12, 18 months doses). Nasopharyngeal/oropharyngeal swabs were obtained at all visits. Serum serotype-specific IgG concentrations and opsonic activities (OPA) were measured at 2, 7, 13 and 19 months. This study was registered with Current Controlled Trials, Ltd. ISRCTN28445844. Overall, 544 infants were enrolled: 3+1 (n = 178), 3+0 (n = 178) and 0+2 (n = 188). Post-priming (7 months), antibody concentrations were similar in both groups, except for serotype 18C (higher in 3+0). Post-booster (13, 19 months), ELISA and OPA levels were significantly higher in 3+1 than in 3+0 group. Nasopharyngeal/oropharyngeal cultures were positive for Streptococcus pneumoniae in 2673 (54.3%) visits. Acquisition rates (vaccine and non-vaccine serotypes) were similar for 3+1 and 3+0 groups at 7-30 months and for 0+2 group at 19-30 months. PCV7 booster after 3 priming doses increased substantially IgG concentrations but did not further reduced vaccine-serotype nasopharyngeal acquisition, suggesting that protection from pneumococcal carriage does not depend primarily on serum IgG. Copyright © 2018 Elsevier Ltd. All rights reserved.

Immunoglobulin G (IgG) Fab glycosylation analysis using a new mass spectrometric high-throughput profiling method reveals pregnancy-associated changes.

PubMed

Bondt, Albert; Rombouts, Yoann; Selman, Maurice H J; Hensbergen, Paul J; Reiding, Karli R; Hazes, Johanna M W; Dolhain, Radboud J E M; Wuhrer, Manfred

2014-11-01

The N-linked glycosylation of the constant fragment (Fc) of immunoglobulin G has been shown to change during pathological and physiological events and to strongly influence antibody inflammatory properties. In contrast, little is known about Fab-linked N-glycosylation, carried by ∼ 20% of IgG. Here we present a high-throughput workflow to analyze Fab and Fc glycosylation of polyclonal IgG purified from 5 μl of serum. We were able to detect and quantify 37 different N-glycans by means of MALDI-TOF-MS analysis in reflectron positive mode using a novel linkage-specific derivatization of sialic acid. This method was applied to 174 samples of a pregnancy cohort to reveal Fab glycosylation features and their change with pregnancy. Data analysis revealed marked differences between Fab and Fc glycosylation, especially in the levels of galactosylation and sialylation, incidence of bisecting GlcNAc, and presence of high mannose structures, which were all higher in the Fab portion than the Fc, whereas Fc showed higher levels of fucosylation. Additionally, we observed several changes during pregnancy and after delivery. Fab N-glycan sialylation was increased and bisection was decreased relative to postpartum time points, and nearly complete galactosylation of Fab glycans was observed throughout. Fc glycosylation changes were similar to results described before, with increased galactosylation and sialylation and decreased bisection during pregnancy. We expect that the parallel analysis of IgG Fab and Fc, as set up in this paper, will be important for unraveling roles of these glycans in (auto)immunity, which may be mediated via recognition by human lectins or modulation of antigen binding. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Immunoglobulin G (IgG) Fab Glycosylation Analysis Using a New Mass Spectrometric High-throughput Profiling Method Reveals Pregnancy-associated Changes*

PubMed Central

Bondt, Albert; Rombouts, Yoann; Selman, Maurice H. J.; Hensbergen, Paul J.; Reiding, Karli R.; Hazes, Johanna M. W.; Dolhain, Radboud J. E. M.; Wuhrer, Manfred

2014-01-01

The N-linked glycosylation of the constant fragment (Fc) of immunoglobulin G has been shown to change during pathological and physiological events and to strongly influence antibody inflammatory properties. In contrast, little is known about Fab-linked N-glycosylation, carried by ∼20% of IgG. Here we present a high-throughput workflow to analyze Fab and Fc glycosylation of polyclonal IgG purified from 5 μl of serum. We were able to detect and quantify 37 different N-glycans by means of MALDI-TOF-MS analysis in reflectron positive mode using a novel linkage-specific derivatization of sialic acid. This method was applied to 174 samples of a pregnancy cohort to reveal Fab glycosylation features and their change with pregnancy. Data analysis revealed marked differences between Fab and Fc glycosylation, especially in the levels of galactosylation and sialylation, incidence of bisecting GlcNAc, and presence of high mannose structures, which were all higher in the Fab portion than the Fc, whereas Fc showed higher levels of fucosylation. Additionally, we observed several changes during pregnancy and after delivery. Fab N-glycan sialylation was increased and bisection was decreased relative to postpartum time points, and nearly complete galactosylation of Fab glycans was observed throughout. Fc glycosylation changes were similar to results described before, with increased galactosylation and sialylation and decreased bisection during pregnancy. We expect that the parallel analysis of IgG Fab and Fc, as set up in this paper, will be important for unraveling roles of these glycans in (auto)immunity, which may be mediated via recognition by human lectins or modulation of antigen binding. PMID:25004930

Laparoscopic surgery contributes more to nutritional and immunologic recovery than fast-track care in colorectal cancer.

PubMed

Xu, Dong; Li, Jun; Song, Yongmao; Zhou, Jiaojiao; Sun, Fangfang; Wang, Jianwei; Duan, Yin; Hu, Yeting; Liu, Yue; Wang, Xiaochen; Sun, Lifeng; Wu, Linshan; Ding, Kefeng

2015-02-04

Many clinical trials had repeatedly shown that fast-track perioperative care and laparoscopic surgery are both preferred in the treatment of colorectal cancer. But few studies were designed to explore the diverse biochemical impacts of the two counterparts on human immunologic and nutritional status. Ninety-two cases of colorectal cancer patients meeting the inclusion criteria were randomized to four groups: laparoscopy with fast-track treatment (LAFT); open surgery with fast-track treatment (OSFT); laparoscopy with conventional treatment (LAC); open surgery with conventional treatment (OSC). Peripheral blood tests including nutritional factors (albumin, prealbumin, and transferrin), humoral immunologic factors (IgG, IgM, and IgA), and cellular immunologic factors (T and NK cells) were evaluated. Blood samples were collected preoperatively (baseline) and 12 and 96 h after surgery (indicated as POH12 and POH96, respectively). Albumin, transferrin, prealbumin, and IgG levels were the highest in the LAFT group for both POH12 and POH96 time intervals. Repeated measures (two-way ANOVA) indicated that the difference of albumin, transferrin, and IgG level were attributed to surgery type (P < 0.05) and not perioperative treatment (P > 0.05). Only in the laparoscopy-included groups, the relative albumin and IgG levels of POH96 were obviously higher than that of POH12. Laparoscopic surgery accelerated postoperative nutrition and immune levels rising again while fast-track treatment retarded the drop of postoperative nutrition and immune levels. Laparoscopic surgery might play a more important role than fast-track treatment in the earlier postoperative recovery of nutritional and immunologic status. Combined laparoscopic surgery with fast-track treatment provided best postoperative recovery of nutrition and immune status. These results should be further compared with the clinical outcomes of our FTMDT trial (clinicaltrials.gov: NCT01080547).

Combined roles of human IgG subclass, alternative complement pathway activation, and epitope density in the bactericidal activity of antibodies to meningococcal factor h binding protein.

PubMed

Giuntini, Serena; Reason, Donald C; Granoff, Dan M

2012-01-01

Meningococcal vaccines containing factor H binding protein (fHbp) are in clinical development. fHbp binds human fH, which enables the meningococcus to resist complement-mediated bacteriolysis. Previously, we found that chimeric human IgG1 mouse anti-fHbp monoclonal antibodies (MAbs) had human complement-mediated bactericidal activity only if the MAb inhibited fH binding. Since IgG subclasses differ in their ability to activate complement, we investigated the role of human IgG subclasses on antibody functional activity. We constructed chimeric MAbs in which three different murine fHbp-specific binding domains were each paired with human IgG1, IgG2, or IgG3. Against a wild-type group B isolate, all three IgG3 MAbs, irrespective of their ability to inhibit fH binding, had bactericidal activity that was >5-fold higher than the respective IgG1 MAbs, while the IgG2 MAbs had the least activity. Against a mutant with increased fHbp expression, the anti-fHbp MAbs elicited greater C4b deposition (classical pathway) and greater bactericidal activity than against the wild-type strain, and the IgG1 MAbs had similar or greater activity than the respective IgG3 MAbs. The bactericidal activity against both wild-type and mutant strains also was dependent, in part, on activation of the alternative complement pathway. Thus, at lower epitope density in the wild-type strain, the IgG3 anti-fHbp MAbs had the greatest bactericidal activity. At a higher epitope density in the mutant, the IgG1 MAbs had similar or greater bactericidal activity than the IgG3 MAbs, and the activity was less dependent on the inhibition of fH binding than at a lower epitope density.

IgG Antibody Responses to Recombinant gp120 Proteins, gp70V1/V2 Scaffolds, and a CyclicV2 Peptide in Thai Phase I/II Vaccine Trials Using Different Vaccine Regimens.

PubMed

Karasavvas, Nicos; Karnasuta, Chitraporn; Savadsuk, Hathairat; Madnote, Sirinan; Inthawong, Dutsadee; Chantakulkij, Somsak; Rittiroongrad, Surawach; Nitayaphan, Sorachai; Pitisuttithum, Punnee; Thongcharoen, Prasert; Siriyanon, Vinai; Andrews, Charla A; Barnett, Susan W; Tartaglia, James; Sinangil, Faruk; Francis, Donald P; Robb, Merlin L; Michael, Nelson L; Ngauy, Viseth; de Souza, Mark S; Paris, Robert M; Excler, Jean-Louis; Kim, Jerome H; O'Connell, Robert J

2015-11-01

RV144 correlates of risk analysis showed that IgG antibodies to gp70V1V2 scaffolds inversely correlated with risk of HIV acquisition. We investigated IgG antibody responses in RV135 and RV132, two ALVAC-HIV prime-boost vaccine trials conducted in Thailand prior to RV144. Both trials used ALVAC-HIV (vCP1521) at 0, 1, 3, and 6 months and HIV-1 gp120MNgD and gp120A244gD in alum (RV135) or gp120SF2 and gp120CM235 in MF59 (RV132) at 3 and 6 months. We assessed ELISA binding antibodies to the envelope proteins (Env) 92TH023, A244gD and MNgD, cyclicV2, and gp70V1V2 CaseA2 (subtype B) and 92TH023 (subtype CRF01_AE), and Env-specific IgG1 and IgG3. Antibody responses to gp120 A244gD, MNgD, and gp70V1V2 92TH023 scaffold were significantly higher in RV135 than in RV132. Antibodies to gp70V1V2 CaseA2 were detected only in RV135 vaccine recipients and IgG1 and IgG3 antibody responses to A244gD were significantly higher in RV135. IgG binding to gp70V1V2 CaseA2 and CRF01_AE scaffolds was higher with the AIDSVAX(®)B/E boost but both trials showed similar rates of antibody decline post-vaccination. MF59 did not result in higher IgG antibody responses compared to alum with the antigens tested. However, notable differences in the structure of the recombinant proteins and dosage used for immunizations may have contributed to the magnitude and specificity of IgG induced by the two trials.

Trace elements, organochlorines, polycyclic aromatic hydrocarbons, dioxins, and furans in lesser scaup wintering on the Indiana Harbor Canal

USGS Publications Warehouse

Custer, T.W.; Custer, Christine M.; Hines, R.K.; Sparks, D.W.

2000-01-01

During the winter of 1993a??94, male lesser scaup (Aythya affinis) were collected on the heavily polluted Indiana Harbor Canal (IHC), East Chicago, IN, USA, and examined for tissue contaminant levels. Lesser scaup collected on the IHC had higher concentrations of cadmium (Cd), mercury (Hg), selenium (Se), polychlorinated biphenyls (PCBs), selected organchlorine pesticides, polychlorinated dibenzodioxins, polychlorinated dibenzofurans, polycyclic aromatic hydrocarbons, and aliphatic hydrocarbons than reference birds. Of the scaup collected on the IHC, 44% had Cd concentrations in the liver considered above background for freshwater waterfowl (>3 I?g/g dry wt.), 50% had Se concentrations in the liver above a level possibly harmful to the health of young and adult birds (>33 I?g/g dry wt.), and 88% of the scaup carcasses exceeded the PCB human consumption guidelines for edible poultry in the USA (>3.0 I?g/g lipid wt.). The ratio of pristane:n-heptadecane concentrations in 47% of lesser scaup collected on IHC was elevated above 1.0, which is indicative of chronic exposure to petroleum hydrocarbons. Copyright A? 2009 Elsevier B.V.

A new type of natural bispecific antibody with potential protective effect in Hashimoto thyroiditis.

PubMed

Li, Wenli; Fan, Gaowei; Chen, Lida; Zhang, Rui; Zhang, Kuo; Sun, Yu; Lin, Guigao; Xie, Jiehong; Wang, Lunan; Li, Jinming

2014-09-01

As a new antibody concept, natural bispecific antibodies (nBsAbs) have been detected in long-term passive immunization and some diseases, but their potential immunomodulatory role remains unclear. Hashimoto thyroiditis (HT) appears to fulfill the condition for nBsAb production but has not yet been characterized. The objective of the study was to identify a new nBsAb against thyroid peroxidase (TPO) and thyroglobulin (Tg) in HT patients and to preliminarily explore its immunomodulatory role. Serum samples were obtained from 136 HT patients, 92 diseased controls, and 99 healthy controls for anti-TPO/Tg nBsAb detection. The relationship between anti-TPO/Tg nBsAb and other clinical parameters was also analyzed. The anti-TPO/Tg nBsAb was detected using a double-antigen sandwich ELISA. Higher nBsAb levels were found to be associated with decreased inflammation in HT patients. The prevalence of anti-TPO/Tg nBsAb in HT was 44.9% (61 of 136), significantly higher than that of diseased controls (2.2%, 2 of 92) (P < .0001) and healthy controls (0%, 0 of 99) (P < .0001). HT patients who were nBsAb positive were prone to have significantly lower levels of serum C-reactive protein and TNF-α compared with the nBsAb-negative individuals (P < .05). The serum amyloid A and interferon-γ levels also showed a similar trend in the two groups. The IgG subclass of anti-TPO/Tg nBsAb was IgG4. Further analysis showed a negative correlation between anti-TPO/Tg nBsAb and serum total IgG4 (r = -0.697, P = .025) in IgG4 thyroiditis patients. A new type of nBsAb against TPO and Tg in HT patients is identified. Our data also indicate a protective effect of anti-TPO/Tg nBsAb in the pathogenesis of HT and extend prior knowledge about nBsAb in diseases.

Variation in the immune responses against Plasmodium falciparum merozoite surface protein-1 and apical membrane antigen-1 in children residing in the different epidemiological strata of malaria in Cameroon.

PubMed

Kwenti, Tebit Emmanuel; Moye, Adzemye Linus; Wiylanyuy, Adzemye Basil; Njunda, Longdoh Anna; Nkuo-Akenji, Theresa

2017-11-09

Studies to assess the immune responses against malaria in Cameroonian children are limited. The purpose of this study was to assess the immune responses against Plasmodium falciparum merozoite surface protein-1 (MSP-1 19 ) and apical membrane antigen-1 (AMA-1) in children residing in the different epidemiological strata of malaria in Cameroon. In a cross-sectional survey performed between April and July 2015, 602 children between 2 and 15 years (mean ± SD = 5.7 ± 3.7), comprising 319 (53%) males were enrolled from five epidemiological strata of malaria in Cameroon including: the sudano-sahelian (SS) strata, the high inland plateau (HIP) strata, the south Cameroonian equatorial forest (SCEF) strata, the high western plateau (HWP) strata, and the coastal (C) strata. The children were screened for clinical malaria (defined by malaria parasitaemia ≥ 5000 parasites/µl plus axillary temperature ≥ 37.5 °C). Their antibody responses were measured against P. falciparum MSP-1 19 and AMA-1 vaccine candidate antigens using standard ELISA technique. A majority of the participants were IgG responders 72.1% (95% CI 68.3-75.6). The proportion of responders was higher in females (p = 0.002) and in children aged 10 years and above (p = 0.005). The proportion of responders was highest in Limbe (C strata) and lowest in Ngaoundere (HIP strata) (p < 0.0001). Similarly, the mean IgG antibody levels were higher in children aged 10 years and above (p < 0.0001) and in Limbe (p = 0.001). The IgG antibody levels against AMA-1 were higher in females (p = 0.028), meanwhile no gender disparity was observed with MSP-1. Furthermore the risk of clinical malaria (p < 0.0001) and the mean parasite density (p = 0.035) were higher in IgG non-responders. A high proportion of IgG responders was observed in this study, suggesting a high degree exposure of the target population to malaria parasites. The immune responses varied considerably across the different strata: the highest levels observed in the C strata and the lowest in the HIP strata. Furthermore, malaria transmission in Cameroon could be categorized into two major groups based on the serological reaction of the children: the southern (comprising C and SCEF strata) and northern (comprising HWP, HIP and SS strata) groups. These findings may have significant implications in the design of future trials for evaluating malaria vaccine candidates in Cameroon.

Aliskiren Regulates Neonatal Fc Receptor and IgG Metabolism with Attenuation of Anti-GBM Glomerulonephritis in Mice.

PubMed

Kang, Ju Hyung; Baik, Haing Woon; Yoo, Seung-Min; Kim, Joo Heon; Cheong, Hae Il; Park, Chung-Gyu; Kang, Hee Gyung; Ha, Il-Soo

2016-01-01

Renin, in addition to its activation of the renin-angiotensin system, binds to the (pro)renin receptor (PRR) and triggers inflammatory and fibrogenic signaling in tissue. In addition, aliskiren, a direct renin inhibitor, has been shown to affect IgG metabolism by altering PRR and neonatal Fc receptors (FcRns). We investigated the effect of aliskiren on proteinuria, glomerular extracellular matrix, expressions of fibronectin, transforming growth factor β1 (TGF-β1), PRR, FcRn and renal metabolism of IgG in a mice model of anti-glomerular basement membrane glomerulonephritis (anti-GBM GN). IgG deposition and expressions of FcRn and PRR were enhanced at glomeruli and urinary IgG levels increased in anti-GBM GN. Aliskiren attenuated anti-GBM GN with reduction of proteinuria and cortical expressions of fibronectin and TGF-β1. In addition, aliskiren suppressed the renal cortical expressions of FcRn and PRR. Aliskiren also reduced the glomerular IgG depositions and the urinary IgG levels albeit with increased circulating serum IgG levels. These results suggest that suppression of FcRn and PRR and regulation of IgG metabolism may be related to the attenuation of anti-GBM GN by aliskiren. © 2016 S. Karger AG, Basel.

IgG4-related prostatitis progressed from localized IgG4-related lymphadenopathy.

PubMed

Li, Dujuan; Kan, Yunzhen; Fu, Fangfang; Wang, Shuhuan; Shi, Ligang; Liu, Jie; Kong, Lingfei

2015-01-01

Immunoglobulin G4-related disease (IgG4-RD) is a recently described inflammatory disease involving multiple organs. Prostate involvement with IgG4-RD is very rare. In this report, we describe a case of IgG4-related prostatitis progressed from localized IgG4-related lymphadenopathy. This patient was present with urine retention symptoms. MRI and CT examination revealed the prostatic enlargement and the multiple lymphadenopathy. Serum IgG4 levels were elevated. Prostatic tissue samples resected both this time and less than 1 year earlier showed the same histological type of prostatitis with histopathologic and immunohistochemical findings characteristic of IgG4-RD. The right submandibular lymph nodes excised 2 years earlier were eventually proven to be follicular hyperplasia-type IgG4-related lymphadenopathy. This is the first case of IgG4-RD that began as localized IgG4-related lymphadenopathy and progressed into a systemic disease involving prostate and multiple lymph nodes. This patient showed a good response to steroid therapy. This leads us to advocate a novel pathogenesis of prostatitis, and a novel therapeutic approach against prostatitis. Pathologists and urologists should consider this disease entity in the patients with elevated serum IgG4 levels and the symptoms of prostatic hyperplasia to avoid ineffective medical or unnecessary surgical treatment.

Humans have antibodies against a plant virus: evidence from tobacco mosaic virus.

PubMed

Liu, Ruolan; Vaishnav, Radhika A; Roberts, Andrew M; Friedland, Robert P

2013-01-01

Tobacco mosaic virus (TMV), a widespread plant pathogen, is found in tobacco (including cigarettes and smokeless tobacco) as well as in many other plants. Plant viruses do not replicate or cause infection in humans or other mammals. This study was done to determine whether exposure to tobacco products induces an immune response to TMV in humans. Using a sandwich ELISA assay, we detected serum anti-TMV antibodies (IgG, IgG1, IgG3, IgG4, IgA, and IgM) in all subjects enrolled in the study (20 healthy smokers, 20 smokeless-tobacco users, and 20 non-smokers). Smokers had a higher level of serum anti-TMV IgG antibodies than non-smokers, while the serum level of anti-TMV IgA from smokeless tobacco users was lower than smokers and non-smokers. Using bioinformatics, we also found that the human protein TOMM40L (an outer mitochondrial membrane 40 homolog--like translocase) contains a strong homology of six contiguous amino acids to the TMV coat protein, and TOMM40L peptide exhibited cross-reactivity with anti-TMV antibodies. People who smoke cigarettes or other tobacco products experience a lower risk of developing Parkinson's disease, but the mechanism by which this occurs is unclear. Our results showing molecular mimicry between TMV and human TOMM40L raise the question as to whether TMV has a potential role in smokers against Parkinson's disease development. The potential mechanisms of molecular mimicry between plant viruses and human disease should be further explored.

Raised serum IgG and IgA antibodies to mycobacterial antigens in rheumatoid arthritis.

PubMed Central

Tsoulfa, G; Rook, G A; Van-Embden, J D; Young, D B; Mehlert, A; Isenberg, D A; Hay, F C; Lydyard, P M

1989-01-01

Autoantigens cross reactive with mycobacteria are implicated in the pathogenesis of adjuvant arthritis in the rat, and there are reports of changes in the immune response to mycobacteria in human rheumatoid arthritis (RA). We have therefore examined the IgM, IgG, and IgA antibody levels to crude mycobacterial antigens and to two recombinant mycobacterial heat shock/stress proteins (65 kD and 71 kD) in sera from patients with RA, systemic lupus erythematosus (SLE), and Crohn's disease, and from healthy controls. IgA binding to the crude mycobacterial antigens was significantly raised in RA sera, though IgG and IgM binding tended to be lower than in controls. Both IgA and IgG binding to the heat shock proteins were significantly raised in the RA sera. Smaller significant rises in both classes were seen in sera from patients with SLE, and in the IgA class only to the 65 kD protein in Crohn's disease. The rises in IgG and IgA antibodies to the 65 kD protein in RA were significantly higher than in the other diseases, however. It is interesting that this protein is the one responsible for adjuvant arthritis in the rat. PMID:2930263

Immunoglobulin patterns in humans over 95 years of age.

PubMed Central

Radl, J; Sepers, J M; Skvaril, F; Morell, A; Hijmans, W

1975-01-01

Immunoglobulin patterns were investigated in seventy-three volunteers older than 95 years. An idiopathic paraproteinaemia was found in 19% of the cases. A restriction of heterogeneity and an imbalance in the kappa/lambda ratio of the immunoglobulins was seen in a number of other sera. Determinations of immunoglobulin levels in sera of individuals without paraproteinaemia showed an increase in IgA and IgG. The quantitations of the IgG subclasses demonstrated that an increase in the IgG1 and IgG3 subclasses is responsible for the elevated level of the IgG. The variation in the immunoglobulin levels increased significantly with age of IgM and for the three major IgG subclasses. No abnormalities were found in the urine or in the mixed saliva. These results indicate that selective changes in the extent of the antibody-immunoglobulin repertoire characterize the immunoglobulin pattern of ageing man. PMID:1212818

Ocular myasthenia gravis induced by human acetylcholine receptor ϵ subunit immunization in HLA DR3 transgenic mice.

PubMed

Wu, Xiaorong; Tuzun, Erdem; Saini, Shamsher S; Wang, Jun; Li, Jing; Aguilera-Aguirre, Leopoldo; Huda, Ruksana; Christadoss, Premkumar

2015-12-01

Extraocular muscles (EOM) are preferentially involved in myasthenia gravis (MG) and acetylcholine receptor (AChR) antibody positive MG patients may occasionally present with isolated ocular symptoms. Although experimental autoimmune myasthenia gravis (EAMG) induced by whole AChR immunization closely mimics clinical and immunopathological aspects of MG, EOM are usually not affected. We have previously developed an EAMG model, which imitates EOM symptoms of MG by immunization of human leukocyte antigen (HLA) transgenic mice with α or γ-subunits of human AChR (H-AChR). To investigate the significance of the ϵ-subunit in ocular MG, we immunized HLA-DR3 and HLA-DQ8 transgenic mice with recombinant H-AChR ϵ-subunit expressed in Escherichia coli. HLA-DR3 transgenic mice showed significantly higher clinical ocular and generalized MG severity scores and lower grip strength values than HLA-DQ8 mice. H-AChR ϵ-subunit-immunized HLA-DR3 transgenic mice had higher serum anti-AChR antibody (IgG, IgG1, IgG2b, IgG2c and IgM) levels, neuromuscular junction IgG and complement deposit percentages than ϵ-subunit-immunized HLA-DQ8 transgenic mice. Control mice immunized with E. coli extract or complete Freund adjuvant (CFA) did not show clinical and immunopathological features of ocular and generalized EAMG. Lymph node cells of ϵ-subunit-immunized HLA-DR3 mice showed significantly higher proliferative responses than those of ϵ-subunit-immunized HLA-DQ8 mice, crude E. coli extract-immunized and CFA-immunized transgenic mice. Our results indicate that the human AChR ϵ-subunit is capable of inducing myasthenic muscle weakness. Diversity of the autoimmune responses displayed by mice expressing different HLA class II molecules suggests that the interplay between HLA class II alleles and AChR subunits might have a profound impact on the clinical course of MG. Copyright © 2015 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

Aquaporin-4 antibodies in patients treated with natalizumab for suspected MS

PubMed Central

Gahlen, Anna; Trampe, Anne-Kathrin; Haupeltshofer, Steffen; Ringelstein, Marius; Aktas, Orhan; Berthele, Achim; Wildemann, Brigitte; Gold, Ralf; Jarius, Sven

2017-01-01

Objective: To evaluate (1) the frequency of aquaporin-4 antibody (AQP4-ab)-seropositive cases among patients treated with natalizumab (NAT) and previously diagnosed with MS (MSNAT) in a nationwide cohort, (2) the clinical course of NAT-treated AQP4-ab–seropositive neuromyelitis optica spectrum disorder (NMOSD) patients (NMONAT), (3) AQP4-ab titers in NMONAT and AQP4-ab–seropositive NMOSD treated with other immunotherapies (NMOIT), and (4) immune mechanisms influencing disease activity in NMONAT. Methods: MSNAT serum samples were retrospectively screened with a cell-based assay for AQP4-IgG and titers determined by ELISA. The annualized relapse rate (ARR) and disability progression were assessed. Serum levels of proinflammatory cytokines (interleukin [IL]-1β, IL-4, IL-6, IL-8, IL-10, IL-17, IL-21, and interferon [IFN]-γ) and the chemokine CXCL-10 of NMONAT patients identified in this (n = 4) and a previous study (n = 5) were measured by cytometric bead array and ELISA. Results: Of the 1,183 MSNAT patients (851 female, median 9 NAT infusions), only 4 (0.33%; 3 female, 1 male) had AQP4-IgG. Of these, 2 fulfilled the 2006 NMO criteria and all met the 2015 NMOSD criteria. The ARR was higher in NMONAT vs MSNAT (p = 0.0182). All 4 NMONAT patients had relapses and 2 had an increase of disability. AQP4-ab titers were higher in NMONAT (n = 9) vs NMOIT (n = 13; p = 0.0059). IL-8, IL-1β, and IFN-γ serum levels were significantly higher, and CXCL-10 was significantly lower in NMONAT vs NMOIT. Conclusions: Misdiagnosis of NMOSD with MS is rare. NAT was not able to control disease activity in NMONAT patients, who had higher serum levels of AQP4-IgG and proinflammatory cytokines than patients with NMOSD treated with other immunotherapies. PMID:28642888

Occurrence of IgG4-related hypophysitis lacking IgG4-bearing plasma cell infiltration during steroid therapy.

PubMed

Ohkubo, Yohsuke; Sekido, Takashi; Takeshige, Keiko; Ishi, Hiroaki; Takei, Masahiro; Nishio, Shin-ichi; Yamazaki, Masanori; Komatsu, Mitsuhisa; Kawa, Shigeyuki; Suzuki, Satoru

2014-01-01

Eight years after an episode of multiple IgG4-related disease, a pituitary mass with panhypopituitarism and a visual disturbance developed in a 70-year-old man under low-dose steroid therapy. A pituitary biopsy revealed findings of lymphocytic hypophysitis with the absence of IgG4-positive plasma cell infiltration. The serum IgG4 level was unremarkable. Although performing a pituitary biopsy and measuring the serum IgG4 level is crucial for making a diagnosis of IgG4-related hypophysitis, it is occasionally difficult to diagnose the disease in patients treated with steroid therapy, as observed in the present case. Based on a review of the diagnosis, conducting a careful assessment is required, especially in men and elderly patients thought to have solitary hypophysitis.

Seroprevalence of dengue IgG antibodies in symptomatic and asymptomatic individuals three years after an outbreak in Zhejiang Province, China.

PubMed

Luo, Shuying; Cui, Weihong; Li, Chan; Ling, Feng; Fu, Tao; Liu, Qiyong; Ren, Jiangping; Sun, Jimin

2018-02-23

Cross-reacting antibodies enhanced dengue infection in humans and antibody dependent enhancement (ADE) have been proposed as early mechanisms underlying DHF/DSS. However, the duration of dengue IgG antibodies in the body as well as factors associated with said duration remain unclear. Blood samples from 59 dengue symptomatic persons and 48 asymptomatic individuals were collected. Study participant demographic information (including age in 2009, gender, and place of residence) were also collected. Serum samples were tested for dengue specific IgG by Panbio dengue IgG indirect enzyme-linked immunosorbent assay (ELISA). Chi-square tests and logistic regression analysis of dengue IgG antibodies seroprevalence divided by gender, age groups, and symptomatic or asymptomatic infection were conducted using the Statistical Package for the Social Sciences. Overall, 70 (65.42%) blood samples were seropositive for dengue IgG antibodies with similar seroprevalences found when dividing by gender and different age groups. However, seroprevalence of dengue IgG antibodies in samples from dengue symptomatic persons was significantly higher than that in samples from asymptomatic individuals (96.61% vs 27.08%) according to multivariable logistic regression analysis, the odds ratio (OR) of the factor was 76.731. Dengue IgG antibodies were detectable in samples from most individuals three years after infection. Dengue symptomatic persons had a higher dengue IgG prevalence compared to asymptomatic individuals.

IgG3 deficiency extends lifespan and attenuates progression of glomerulonephritis in MRL/lpr mice

PubMed Central

2012-01-01

Background Antibodies of the IgG3 subclass have been implicated in the pathogenesis of the spontaneous glomerulonephritis observed in mice of the MRL/MpJ-Tnfrsf6lpr (MRL/lpr) inbred strain which have been widely studied as a model of systemic lupus erythematosus We have produced IgG3-deficient (-/-) mice with the MRL/lpr genetic background to determine whether IgG3 antibodies are necessary for or at least contributory to MRL/lpr-associated nephritis. Results The gamma3 genotype (+/+ vs. +/- vs. -/-) did not appear to significantly affect serum titers of IgG auto-antibodies specific for double-stranded DNA (dsDNA) or α-actinin. However, while substantial serum titers of IgG3 auto-antibodies specific for double-stranded DNA (dsDNA) or α-actinin were seen in gamma3 +/+ mice, somewhat lower serum titers of these IgG3 auto-antibodies were found in gamma3 +/- mice, and gamma3 -/- mice exhibited baseline concentrations of these auto-antibodies. Analysis of immunoglobulins eluted from snap-frozen kidneys obtained from mice of all three gamma3 genotypes at ~18 weeks of age revealed much higher quantities of IgG in the kidneys from gamma3 +/+ than gamma3 -/- mice, and most IgG eluted from +/+ mice was IgG3. The serum creatinine levels in gamma3 +/+ mice substantially exceeded those of age-matched gamma3 -/- mice after ~21 weeks of age. Histopathological examination of kidneys from mice sacrificed at pre-determined ages also revealed more extensive glomerulosclerosis in gamma3 +/+ or +/- mice than in -/- mice beginning at 21 weeks of age. Survival analysis for IgG3-deficient and IgG3-producing MRL/lpr mice revealed that gamma3 -/- mice lived significantly longer (p = 0.0006) than either gamma3 +/- or +/+ mice. Spontaneous death appeared to be due to irreversible renal failure, because > 85% of glomeruli in kidneys from mice that died spontaneously were obliterated by glomerulosclerosis. Conclusions The available evidence suggests that IgG3 deficiency partially protects MRL/lpr mice against glomerulonephritis-associated morbidity and mortality by slowing or arresting the progression to glomerulosclerosis. Reviewers This article was reviewed by Pushpa Pandiyan, Irun Cohen, and Etienne Joly. PMID:22248284

Low-molecular-weight polysaccharides from Agaricus blazei Murrill modulate the Th1 response in cancer immunity.

PubMed

Jiang, Liyan; Yu, Zhipu; Lin, Yu; Cui, Liran; Yao, Shujuan; Lv, Liyan; Liu, Jicheng

2018-03-01

To assess the effect of low-molecular-weight polysaccharides from Agaricus blazei Murrill (ABP-AW1) as an immunoadjuvant therapy for type 1 T-helper (Th1) responses in tumorigenesis, C57BL/6 mice were inoculated subcutaneously with ovalbumin (E.G7-OVA). After 3, 10 and 17 days, the mice were immunized with PBS, OVA alone, or OVA and ABP-AW1, at low (50 µg), intermediate (100 µg) or high (200 µg) doses. Tumor growth was examined and compared among the groups, as were the following parameters: Splenocyte viability/proliferation, peripheral blood CD4 + /CD8 + T cell ratio, serum OVA-specific IgG1 and IgG2b, secretion of interleukin (IL)-2 and interferon (IFN)-γ, and IFN-γ production on a single cell level from cultured splenocytes. Tumor growth in mice treated with OVA and ABP-AW1 (100 or 200 µg) was significantly slower, compared with in the other groups at the same time-points. OVA with 100 or 200 µg ABP-AW1 was associated with a higher number of total splenocytes, a higher ratio of peripheral blood CD4 + /CD8 + T-lymphocytes, higher serum levels of OVA-specific Th1-type antibody IgG2b and greater secretion of the Th1 cytokines IL-1 and IFN-γ from splenocytes. ABP-AW1 is a promising immunoadjuvant therapy candidate, due to its ability to boost the Th1 immune response when co-administered with a cancer vaccine intended to inhibit cancer progression.

Low-molecular-weight polysaccharides from Agaricus blazei Murrill modulate the Th1 response in cancer immunity

PubMed Central

Jiang, Liyan; Yu, Zhipu; Lin, Yu; Cui, Liran; Yao, Shujuan; Lv, Liyan; Liu, Jicheng

2018-01-01

To assess the effect of low-molecular-weight polysaccharides from Agaricus blazei Murrill (ABP-AW1) as an immunoadjuvant therapy for type 1 T-helper (Th1) responses in tumorigenesis, C57BL/6 mice were inoculated subcutaneously with ovalbumin (E.G7-OVA). After 3, 10 and 17 days, the mice were immunized with PBS, OVA alone, or OVA and ABP-AW1, at low (50 µg), intermediate (100 µg) or high (200 µg) doses. Tumor growth was examined and compared among the groups, as were the following parameters: Splenocyte viability/proliferation, peripheral blood CD4+/CD8+ T cell ratio, serum OVA-specific IgG1 and IgG2b, secretion of interleukin (IL)-2 and interferon (IFN)-γ, and IFN-γ production on a single cell level from cultured splenocytes. Tumor growth in mice treated with OVA and ABP-AW1 (100 or 200 µg) was significantly slower, compared with in the other groups at the same time-points. OVA with 100 or 200 µg ABP-AW1 was associated with a higher number of total splenocytes, a higher ratio of peripheral blood CD4+/CD8+ T-lymphocytes, higher serum levels of OVA-specific Th1-type antibody IgG2b and greater secretion of the Th1 cytokines IL-1 and IFN-γ from splenocytes. ABP-AW1 is a promising immunoadjuvant therapy candidate, due to its ability to boost the Th1 immune response when co-administered with a cancer vaccine intended to inhibit cancer progression. PMID:29467867

Seroepidemiology of Toxoplasma gondii infection in Tepehuanos in Durango, Mexico.

PubMed

Alvarado-Esquivel, Cosme; Estrada-Martínez, Sergio; García-López, Claudia Rosalba; Rojas-Rivera, Amparo; Sifuentes-Álvarez, Antonio; Liesenfeld, Oliver

2012-02-01

The epidemiology of Toxoplasma gondii infection is known to depend on a number of behavioral factors, including contact with animals and eating habits. The epidemiology in specific populations (i.e., in indigenous ethnic groups) is not well studied. We therefore investigated the presence of anti-Toxoplasma IgG and IgM antibodies in 156 Tepehuanos, an indigenous ethnic group in Durango State in northern Mexico, using ELISAs. Of the 156 Tepehuanos (mean age 31.03±16.71 years), 35 (22.4%) had anti-Toxoplasma IgG antibodies. IgG levels of 14-99, 100-150, and >150 IU/mL were found in 15 (42.9%), 1 (2.8%), and 19 (54.3%) anti-Toxoplasma IgG-positive Tepehuanos, respectively. Also, 15 (9.6%) subjects had anti-Toxoplasma IgM antibodies. Male Tepehuanos aged 31-50 years showed a significantly higher frequency of exposure to T. gondii than female Tepehuanos of the same age. Seroprevalence of anti-T. gondii IgM antibodies was significantly higher in Tepehuanos without education than those with 7-12 years of education. Tepehuanos suffering from frequent headaches had significantly higher seroprevalences of anti-T. gondii IgG and IgM antibodies than those without this clinical feature. In addition, Tepehuanos suffering from hearing impairment had significantly higher seroprevalence of anti-T. gondii IgM antibodies than those without this clinical feature. Logistic regression analysis did not show an association of T. gondii exposure with any behavioral characteristics, including contact with cats or eating habits. The seroprevalence of T. gondii exposure in Tepehuanos is comparable to that reported in other populations in North America; however, seroprevalence in the largely rural Tepehuanos is higher than that reported in a nearby urban center. Toxoplasma may be impacting the health of Tepehuanos. This is the first report of T. gondii infection in Tepehuanos, and the results should prove useful for the design of preventive measures.

Assessment of IgG Antibodies Against HSV1, HSV2, CMV and EBV in Patients with Pemphigus Vulgaris Versus Healthy People.

PubMed

Ghalayani, Parichehr; Rashidi, Fateme; Saberi, Zahra

2015-11-01

Regarding the implication of viruses particularly herpes in pemphigus vulgaris, we sought to assess and compare the level of immunoglobulin G (IgG) antibodies against herpes simplex virus types 1 and 2 (HSV1 and HSV2), cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in patients with pemphigus vulgaris and healthy people. In this cross-sectional study, 25 patients with pemphigus vulgaris and 27 healthy individuals comprised the experimental and control groups, respectively. Serum samples were taken from both groups; the levels of IgG antibodies against HSV1, HSV2, CMV and EBV were measured using ELISA. Immunoglobulin G titer was higher for all four viruses in the patient group in comparison to the control group. This difference was significant for anti-EBV (P= 0.005), anti-CMV (P=0.0001) and anti-HSV2 (P=0.001) but not significant for anti-HSV1 (P= 0.36). Viruses including EBV, CMV, and HSV2 probably play a role in the pathogenesis of pemphigus in addition to the effects of genetics, toxins and other predisposing factors. In this study, no statistically significant relationship was observed between HSV1 and pemphigus vulgaris, which was probably due to the high titer of anti-HSV1 IgG in healthy individuals in the community. More studies must be done in this regard.

Mistletoe lectins enhance immune responses to intranasally co-administered herpes simplex virus glycoprotein D2

PubMed Central

Lavelle, E C; Grant, G; Pusztai, A; Pfüller, U; Leavy, O; McNeela, E; Mills, K H G; O'Hagan, D T

2002-01-01

The mucosal adjuvant properties of the three type 2 ribosome-inactivating proteins (RIPs) from the European mistletoe, Viscum album L., were investigated. Mistletoe lectins were compared with cholera toxin (CT) as adjuvants when delivered nasotracheally together with herpes simplex virus glycoprotein D2 (gD2). All three mistletoe lectins (MLI, MLII, MLIII) were potent mucosal adjuvants. Co-administration of MLI, MLII or MLIII with gD2 led to significantly higher levels of gD2-specific mucosal immunoglobulin A (IgA) and systemic immunoglobulin G (IgG) antibody than when the antigen was delivered alone. The levels of antibodies induced were similar to those generated in mice immunized with gD2 and the potent mucosal adjuvant CT. Administration of ML1 with gD2 enhanced the antigen-specific splenic T-cell proliferative response. Interleukin-5 (IL-5), but not interferon-γ (IFN-γ), was detected in supernatants from splenocytes stimulated in vitro with gD2. This indicates that MLI enhanced type 2 T-helper cell (Th2) responses to the bystander antigen, gD2. Analysis of the gD2- and lectin-specific IgG subclass titres in mice immunized with gD2 and MLI, MLII or MLIII revealed a high ratio of IgG1 : IgG2a, which is compatible with the selective induction of Th2-type immune responses. PMID:12383207

Whole-cell or acellular pertussis vaccination in infancy determines IgG subclass profiles to DTaP booster vaccination.

PubMed

van der Lee, Saskia; Sanders, Elisabeth A M; Berbers, Guy A M; Buisman, Anne-Marie

2018-01-04

Duration of protection against pertussis is shorter in adolescents who have been immunized with acellular pertussis (aP) in infancy compared with adolescents who received whole-cell pertussis (wP) vaccines in infancy, which is related to immune responses elicited by these priming vaccines. To better understand differences in vaccine induced immunity, we determined pertussis, diphtheria, and tetanus (DTaP) vaccine antigen-specific IgG subclass responses in wP- and aP-primed children before and after two successive DTaP booster vaccinations. Blood samples were collected in a cross-sectional study from wP- or aP-primed children before and 1 month after the pre-school DTaP booster vaccination at age 4 years. Blood samples were collected from two different wP- and aP-primed groups of children before, 1 month and 1 year after an additional pre-adolescent Tdap booster at age 9 years. IgG subclass levels against the antigens included in the DTaP vaccine have been determined with fluorescent-bead-based multiplex immunoassays. At 4 years of age, the IgG4 proportion and concentration for pertussis, diphtheria and tetanus vaccine antigens were significantly higher in aP-primed children compared with wP-primed children. IgG4 concentrations further increased upon the two successive booster vaccinations at 4 and 9 years of age in both wP- and aP-primed children, but remained significantly higher in aP-primed children. The pertussis vaccinations administered in the primary series at infancy determine the vaccine antigen-specific IgG subclass profiles, not only against the pertussis vaccine antigens, but also against the co-administered diphtheria and tetanus vaccine antigens. These profiles did not change after DTaP booster vaccinations later in childhood. The different immune response with high proportions of specific IgG4 in some aP-primed children may contribute to a reduced protection against pertussis. ISRCTN65428640; ISRCTN64117538; NTR4089. Copyright © 2017 Elsevier Ltd. All rights reserved.

Development of a polyclonal anti-dugong immunoglobulin G (IgG) antibody with evaluation of total plasma IgG in a living dugong (Dugong dugon) population.

PubMed

Wong, Arthur; Lanyon, Janet M; McKee, Sara J; Linedale, Richard; Woolford, Lucy; Long, Trevor; Leggatt, Graham R

2018-06-01

Species-specific antibodies (Ab) for the measurement of immunoglobulins (Ig) are valuable tools for determining the humoral immune status of threatened and endangered wildlife species such as dugongs. However, no studies have reported antibody reagents against dugong immunoglobulin. The object of this study was to develop an Ab with specificity for dugong IgG and apply this tool to survey total IgG levels in plasma samples from a live wild population of dugongs in southern Queensland, Australia. Dugong IgG was isolated from plasma by protein A/G column chromatography and a polyclonal antiserum was successfully raised against the dugong IgG through immunization of mice. The anti-dugong antiserum was reactive with dugong serum but not immunoglobulin from other species such as rats and humans. When tested against a panel of dugong plasma samples, relative IgG levels from dugongs (n = 116) showed biologically relevant relationships with pregnancy status and a principal component of Body Mass Index (BMI)/globulin/fecal glucocorticosteroid (chronic stress) levels combined, which together accounted for 9.2% of the variation in total Ig levels. Together these data suggest that dugongs show variation in total IgG and that this correlates with some physiological parameters of dugong health. Copyright © 2018 Elsevier B.V. All rights reserved.

Immunoglobulin and antibody levels in bronchoalveolar lavage fluid from symptomatic and asymptomatic pigeon breeders.

PubMed Central

Reynolds, S P; Edwards, J H; Jones, K P; Davies, B H

1991-01-01

Twenty-one symptomatic subjects with pigeon breeders' lung (PBL) and 10 asymptomatic pigeon breeders, with a similar exposure to pigeon antigens, underwent bronchoalveolar lavage. Total IgG, IgM and IgA in lavage fluid were determined as were specific antibody levels against antigens in pigeon serum and droppings. Results were converted to levels in epithelial lining fluid (ELF) using lavage and serum urea ratios. It was found that symptomatics represent a group that is hyperreactive to pigeon antigens compared with the asymptomatic group with significantly higher IgG, IgM, IgA levels as well as specific antibody levels against pigeon serum and droppings. Paired serum and ELF samples from 12 symptomatic subjects showed significantly elevated IgG, IgM and IgA levels in ELF compared with serum when values were expressed in terms of albumin. This strongly supports the concept of local production of immunoglobulins within the lung after inhaling immunogens as opposed to their diffusion from the vasculature. Results for IgA indicate that any putative protective role for this immunoglobulin is not valid in relation to the prevention of extrinsic allergic alveolitis. Analysis of smoking habits, lung immunoglobulins and response to inhalation challenge confirm the negative influence of smoking on total and functional lung immunoglobulins; however, levels in the ELF of ex-smokers suggest that the effect of smoking is not permanent. Smoking did not prevent responses to inhalation challenge. PMID:1934595

Presence of keratin-specific antibody-forming cells in palatine tonsils of patients with pustulosis palmaris et plantaris (PPP) and its correlation with prognosis after tonsillectomy.

PubMed

Tanimoto, Yoichiro; Fukuyama, Satoshi; Tanaka, Norimitsu; Ohori, Jun-Ichiro; Tanimoto, Yukari; Kurono, Yuichi

2014-01-01

Keratin-specific immune responses in tonsils may be associated with the pathogenesis of pustulosis palmaris et plantaris (PPP). Evaluation of keratin-specific immune responses in tonsils might be useful to predict the effectiveness of tonsillectomy for patients with PPP. The aim of the present study was to clarify the role of keratin-specific immune responses in the pathogenesis of PPP in tonsils. It has been reported that anti-keratin antibodies in serum were higher in patients with PPP and decreased after tonsillectomy, indicating that anti-keratin antibodies might be generated in tonsils. In order to demonstrate the presence of keratin-specific immune responses in tonsils, the numbers of keratin-specific antibody-forming cells (AFCs) in tonsillar and peripheral blood lymphocytes were examined by enzyme-linked immunospot assay. The prognosis of PPP was compared after tonsillectomy. The numbers of keratin-specific IgM and IgG AFCs in tonsils and of IgG AFCs in peripheral blood were significantly increased in patients with PPP. The numbers of keratin-specific IgG AFCs in peripheral blood correlated positively with tonsil and serum IgG antibodies specific to keratin. Our data show that a good prognosis in patients with PPP depended on the numbers of keratin-specific IgG and IgM AFCs in peripheral blood and the levels of keratin-specific IgG antibodies in serum being significantly decreased 6 months after tonsillectomy.

Seroprevalence of toxoplasma-specific antibodies in patients suspected to have active toxoplasmosis: A cross-sectional survey.

PubMed

Eskandarian, Abbas Ali; Jafarnezghad, Gholam-Abbas; Akbari, Mojtaba

2014-01-01

The aim of this study was to investigate the presence and distribution of anti-toxoplasma-specific IgM and IgG tantibodies in patients suspected to have toxoplasmosis and investigate for any association between IgM and IgG antibodies and some toxoplasmosis risk factors as well. In a comparative cross-sectional study, 70 patients suspected to had active toxoplasmosis and 30 control volunteers, who gave informed consent, entered the study. In each group, patient age, sex, signs of appearance, education level, residency status (urban / rural), occupation, frequency of toxoplasma-specific IgG and IgM antibodies, abortion history, and some risk factors (Direct cat exposure, Occupational exposure to raw meat, and Raw vegetable consumption) were recorded. The enzyme-linked immunosorbent assay (ELISA) kits (EUROIMMUN(®), United Kingdom) were used for the evaluation of anti-toxoplasma IgG and IgM antibodies according to the manufacturer's instructions. All analyses were done using SPSS-20. The frequency of toxoplasma-specific IgG and IgM antibodies like: Direct cat exposures, Occupational exposure to raw meat, and Raw vegetable consumption were not statistically significant between the two groups (P > 0.05). The history of previous abortions in women in the toxoplasmosis-suspected group was significantly higher than that in the controls (31.4% versus 6.7%; P = 0.009). The frequency of specific IgM and IgG antibodies in toxoplasmosis suspected in the toxoplasmosis and control groups was not statistically significant.

Clinical evaluation of the new Roche platform of serological and molecular cytomegalovirus-specific assays in the diagnosis and prognosis of congenital cytomegalovirus infection.

PubMed

Chiereghin, Angela; Pavia, Claudia; Gabrielli, Liliana; Piccirilli, Giulia; Squarzoni, Diego; Turello, Gabriele; Gibertoni, Dino; Simonazzi, Giuliana; Capretti, Maria Grazia; Lanari, Marcello; Lazzarotto, Tiziana

2017-10-01

Clinical evaluation of the Elecsys ® CMV IgM, IgG, IgG Avidity and COBAS AmpliPrep/COBAS TaqMan CMV (COBAS CMV) assays (Roche Diagnostics AG) in the diagnosis and prognosis of congenital CMV infection was performed. In this study, 150 preselected clinical samples (50 primary infection sera, 50 amniotic fluid [AF] and 50 newborn urine) were processed using Roche serological/molecular CMV-specific tests. Results were compared with those obtained by routine assays (comparator assays). The Elecsys ® CMV IgM and IgG assays showed a perfect agreement (100%) with the comparator assays. Using the combination of the Elecsys ® CMV IgM and IgG Avidity assays results, a primary infection was identified in 100% of cases. Inappropriate avidity CMV IgG values in two samples with very low IgG values (<6 AU/mL) were observed. COBAS CMV assay showed an agreement equal to 98% and 100% with comparator assays by processing AF and urine samples, respectively. Among AF with quantitative results, Lin's concordance correlation was 0.933 and comparator-COBAS CMV assays gave CMV-DNA loads differing by <0.5 log 10 DNA. Finally, higher CMV-DNA levels in AF samples were associated with a symptomatic outcome (p=0.003). The Roche CMV-specific assays compared well with the comparator assays, thus providing to be suitable for clinical use. Copyright © 2017 Elsevier B.V. All rights reserved.

Salivary IgG subclasses in individuals with and without homozygous IGHG gene deletions.

PubMed Central

Engström, P E; Norhagen, G; Osipova, L; Helal, A; Wiebe, V; Brusco, A; Carbonara, A O; Lefranc, G; Lefranc, M P

1996-01-01

In this study, the levels of salivary IgG1, IgG2, IgG3 and IgG4 from individuals with and without homozygous immunoglobulin heavy chain constant gene deletions were quantified by enzyme-linked immunosorbent assay (ELISA). To analyse the restriction of salivary IgG subclasses, we used unstimulated whole saliva and sera collected at the same time from individuals with homozygous gene deletions, two with G1 deletion, one with G4 deletion, six with both G2 and G4 deletions and from eight individuals without IGHG gene deletions and expressing all four IgG subclasses. The median values of salivary IgG from individuals with homozygous G1, or G4, or both G2 and G4 deletions, and from individuals expressing all four subclasses were 24.2 mg/l and 23.4 mg/l, respectively. The median values of serum IgG were 13.7 g/l and 15.9 g/l, respectively. Our results show that the salivary and serum IgG levels were both within the normal range in individuals with homozygous gene deletions of either G1, or G4, or both G2 and G4. PMID:8943711

Intraperitoneally administered IgG from patients with amyotrophic lateral sclerosis or from an immune-mediated goat model increase the levels of TNF-α, IL-6, and IL-10 in the spinal cord and serum of mice.

PubMed

Obál, Izabella; Klausz, Gergely; Mándi, Yvette; Deli, Mária; Siklós, László; Engelhardt, József I

2016-05-24

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that involves the selective loss of the upper and lower motor neurons (MNs). Neuroinflammation has been implicated in the pathogenesis of the sporadic form of the disease. We earlier developed immune-mediated animal models of ALS and demonstrated humoral and cellular immune reactions in the nervous system and in the sera of patients and animals. The accumulation of immunoglobulin G (IgG), an elevated intracellular level of calcium, ultrastructural alterations in the MNs, and activation of the microglia were noted in the spinal cord of ALS patients. Similar alterations developed in mice inoculated intraperitoneally with IgG from ALS patients or from an immune-mediated goat model. We have now examined whether the intraperitoneal injection of mice with IgG from sporadic ALS patients or from immunized goats with the homogenate of the anterior horn of the bovine spinal cord is associated with changes in the pro-inflammatory (TNF-α and IL-6) and anti-inflammatory (IL-10) cytokines in the spinal cord and serum of the mice. The levels of cytokines were measured by ELISA. Intraperitoneally administered IgG from the ALS patients induced subclinical signs of MN disease, while the injection of IgG from immunized goats resulted in a severe respiratory dysfunction and limb paralysis 24 h after the injections. Significantly increased levels of TNF-α and IL-10 were detected in the spinal cord of the mice injected with the human ALS IgG. The level of IL-6 increased primarily in the serum. The IgG from the immunized goats induced highly significant increases in the levels of all three cytokines in the serum and the spinal cord of mice. Our earlier experiments had proved that when ALS IgG or IgG from immune-mediated animal models was inoculated into mice, it was taken up in the MNs and had the ability to initiate damage in them. The pathological process was paralleled by microglia recruitment and activation in the spinal cord. The present experiment revealed that these forms of IgG cause significant increases in certain cytokine levels locally in the spinal cord and in the serum of the inoculated mice. These results suggest that IgG directed to the MNs may be an initial element in the damage to the MNs both in human ALS and in its immune-mediated animal models.

Expression of human FcgammaRIIIa as a GPI-linked molecule on CHO cells to enable measurement of human IgG binding.

PubMed

Armour, Kathryn L; Smith, Cheryl S; Clark, Michael R

2010-03-31

The efficacy of a therapeutic IgG molecule may be as dependent on the optimisation of the constant region to suit its intended indication as on the selection of its variable regions. A crucial effector function to be maximised or minimised is antibody-dependent cell-mediated cytotoxicity by natural killer cells. Traditional assays of ADCC activity suffer from considerable inter-donor and intra-donor variability, which makes the measurement of antibody binding to human FcgammaRIIIa, the key receptor for ADCC, an attractive alternative method of assessment. Here, we describe the development of cell lines and assays for this purpose. The transmembrane receptor, FcgammaRIIIa, requires co-expression with signal transducing subunits to prevent its degradation, unlike the homologous receptor FcgammaRIIIb that is expressed as a GPI-anchored molecule. Therefore, to simplify the production of cell lines as reliable assay components, we expressed FcgammaRIIIa as a GPI-anchored molecule. Separate, stable CHO cell lines that express either the 158F or the higher-affinity 158V allotype of FcgammaRIIIa were isolated using fluorescence-activated cell sorting. The identities of the expressed receptors were confirmed using a panel of monoclonal antibodies that distinguish between subclasses and allotypes of FcgammaRIII and the cell lines were shown to have slightly higher levels of receptor than FcgammaRIII-positive peripheral blood mononuclear cells. Because the affinity of FcgammaRIIIa for IgG is intermediate amongst the receptors that bind IgG, we were able to use these cell lines to develop flow cytometric assays to measure the binding of both complexed and monomeric immunoglobulin. Thus, by choosing the appropriate method, weakly- or strongly-binding IgG can be efficiently compared. We have quantified the difference in the binding of wildtype IgG1 and IgG3 molecules to the two functional allotypes of the receptor and report that the FcgammaRIIIa-158V-antibody interaction is 3- to 4-fold stronger that the interaction with FcgammaRIIIa-158F. Overall, these robust assays should be valuable for batch-testing clinical material as well as providing tools for improving the design of therapeutic IgG. 2010 Elsevier B.V. All rights reserved.

What do anti-Toxoplasma gondii IgA and IgG subclasses in human saliva indicate?

PubMed

Cañedo-Solares, I; Gómez-Chávez, F; Luna-Pastén, H; Ortiz-Alegría, L B; Flores-García, Y; Figueroa-Damián, R; Macedo-Romero, C A; Correa, D

2018-05-01

Diagnostic tests for toxoplasmosis are based on serological techniques due to their high sensitivity. Some IgG subclasses are related to clinical outcome in the congenital form. In this work, we determined the levels of IgG, IgA, IgG1, IgG2, IgG3 and IgG4 anti-Toxoplasma gondii antibodies in paired saliva and serum samples from 91 women by indirect ELISA using a crude extract of the RH strain. The levels of IgA, IgG2, IgG3 and IgG4 antibodies and, to a lesser extent, IgG1 did not correlate between saliva and serum, that is, most cases that were positive for one Ig class in a sample were negative or very low in the other, and vice versa. We also observed that most samples of saliva that were positive for one IgG subclass were also positive for at least 2 of the other 3; this contrasted with findings in serum, wherein each person was positive almost exclusively for one subclass, as demonstrated before by us and other researchers. Although these findings are disappointing for the use in diagnosis, the richer response in saliva might indicate local exposure to T. gondii antigens without systemic infection; thus, saliva might be reflecting a local (protective?) response against this protozoan. © 2018 John Wiley & Sons Ltd.

High natural antibody titers of indigenous chickens are related with increased hazard in confinement

PubMed Central

Wondmeneh, E.; Van Arendonk, J. A. M.; Van der Waaij, E. H.; Ducro, B. J.; Parmentier, H. K.

2015-01-01

Natural antibody (NAb) levels and survival rates were evaluated in 4 breeds of laying hens in Ethiopia: indigenous, improved indigenous, exotic layer, and crossbred. Titers of NAb isotypes IgG and IgM binding keyhole limpet hemocyanin (KLH) in serum were measured at 20, 26, 35, and 45 wk age. Repeated-measure ANOVA showed that IgG and IgM levels vary with time within each breed (P < 0.05). Indigenous chickens had significantly (P < 0.05) higher NAb levels at all ages. The Cox proportional hazard analysis showed increased hazard with increased levels of NAbs in the exotic layers (P < 0.05). However, the reduced hazards with increased levels of NAbs were not significant in the improved indigenous and crossbred chickens. Indigenous chickens showed increased hazard with increasing levels of NAb (P > 0.05). We concluded that not only the NAb levels but also the effect of Nabs on survival vary between indigenous and improved breeds. The results indicate that NAb levels are associated with survival in elite (improved) breeds, but are associated with increased hazard in indigenous chickens. PMID:25910906

Serum IgG, IgM and slow alpha-globulin levels in carrageenan-treated rats.

PubMed Central

Fowler, E. F.; Thomson, A. W.

1979-01-01

Serum levels of IgM, IgG, slow alpha 1- and slow alpha 2-globulins were measured either by quantitative radial immunodiffusion (IgG) or immunoelectrophoresis (IgM and slow alpha-globulins) during the 3-week period after i.p. injection of 50 mg potassium carrageenan. There was a significant elevation in levels of IgM and slow alpha 1-globulin, maximal on Day 4 and returning to normal by Day 14. Slow alpha 2-globulin was detectable within 24 h, reached a peak at Day 2, and was no longer measurable in most rats by Day 14. Levels of IgG however, were unaffected by carrageenan injection. PMID:92333

Bee sting allergy in beekeepers.

PubMed

Eich-Wanger, C; Müller, U R

1998-10-01

Beekeepers are strongly exposed to honey bee stings and therefore at an increased risk to develop IgE-mediated allergy to bee venom. We wondered whether bee venom-allergic beekeepers were different from normally exposed bee venom-allergic patients with regard to clinical and immunological parameters as well as their response to venom immunotherapy. Among the 459 bee venom-allergic patients seen over the 5 year period 1987-91, 62 (14%) were beekeepers and 44 (10%) family members of beekeepers. These two groups were compared with 101 normally exposed bee venom-allergic patients matched with the allergic beekeepers for age and sex, regarding clinical parameters, skin sensitivity, specific IgE and IgG antibodies to bee venom as well as safety and efficacy of venom immunotherapy. As expected, allergic beekeepers had been stung most frequently before the first allergic reaction. The three groups showed a similar severity of allergic symptoms following bee stings and had an equal incidence of atopic diseases. Allergic beekeepers showed higher levels of bee venom-specific serum IgG, lower skin sensitivity and lower levels of bee venom specific serum IgE than bee venom-allergic control patients. A negative correlation between number of stings and skin sensitivity as well as specific IgE was found in allergic beekeepers and their family members, while the number of stings was positively correlated with specific IgG in these two groups. Venom immunotherapy was equally effective in the three groups, but better tolerated by allergic beekeepers than the two other groups. The majority of allergic beekeepers continued bee-keeping successfully under the protection of venom immunotherapy. The lower level of sensitivity in diagnostic tests and the better tolerance of immunotherapy in allergic beekeepers is most likely related to the high level of specific IgG in this group.

Use of OM-85 BV in children suffering from recurrent respiratory tract infections and subnormal IgG subclass levels.

PubMed

Del-Río-Navarro, B E; Luis Sienra-Monge, J J; Berber, A; Torres-Alcántara, S; Avila-Castañón, L; Gómez-Barreto, D

2003-01-01

Recurrent acute respiratory tract infections (RARTIs) in children are related to IgG subclass deficiencies. The aim of the trial was to evaluate the effect of OM-85 BV in the number of RARTIs as well as in the IgG subclass levels. This was a randomized, double-blind, placebo-controlled clinical trial. Patients of ages three to six years, having three or more documented ARTIs during the last six months with subnormal IgG subclass levels were included. Patients took either one capsule of OM-85 BV (3.5 mg) or placebo orally every day for ten consecutive days per month during three consecutive months. Patients were followed three further months without drug intake. IgG subclass levels were determined before and after treatment. IgG4 levels diminished after the OM-85 BV treatment (-3 [-8.0, -1.0] median difference [95 % CI] p < 0.05 by Wilcoxon test). No other significant changes in IgG subclasses were observed. After six months the patients in the OM-85 BV group (n = 20) experienced 2.8 1.4 (mean SD) ARTIs, while the patients in the placebo group (n = 20) suffered 5.2 1.5 ARTIs (-2.4 [3.3, -1.5] mean difference [95 % CI] p < 0.001 by Student's t test). Three patients with OM-85 BV had gastrointestinal events related to drug administration, as well as three placebo patients. This study demonstrated the clinical benefit of OM-85 BV in patients suffering from RARTIs and subnormal levels of IgG subclasses. This trial opens new perspectives in the research of the mechanism of action of OM-85 BV.

Cytophilic antibodies to Plasmodium falciparum glutamate rich protein are associated with malaria protection in an area of holoendemic transmission.

PubMed

Lusingu, John P A; Vestergaard, Lasse S; Alifrangis, Michael; Mmbando, Bruno P; Theisen, Michael; Kitua, Andrew Y; Lemnge, Martha M; Theander, Thor G

2005-09-29

Several studies conducted in areas of medium or low malaria transmission intensity have found associations between malaria immunity and plasma antibody levels to glutamate rich protein (GLURP). This study was conducted to analyse if a similar relationship could be documented in an area of intense malaria transmission. A six month longitudinal study was conducted in an area of holoendemic malaria transmission in north-eastern Tanzania, where the incidence of febrile malaria decreased sharply by the age of three years, and anaemia constituted a significant part of the malaria disease burden. Plasma antibodies to glutamate rich protein (GLURP) were analysed and related with protection against malaria morbidity in models correcting for the effect of age. The risk of febrile malaria episodes was reduced significantly in children with measurable anti-GLURP IgG1 antibodies at enrollment [adjusted odds ratio: 0.39 (95% CI: 0.15, 0.99); P = 0.047]. Interestingly, there was an inverse relationship between the plasma anti-GLURP IgG1 and IgG3 levels and the levels of parasitaemia at enrollment. However, anti-GLURP IgG2 and IgG4 levels were not associated with reduction in parasite density. Similarly, antibody levels were not associated with haemoglobin levels or anaemia risk. Cytophilic IgG1 and IgG3 antibodies against R0-GLURP may contribute to the control of parasite multiplication and reduction in febrile malaria incidence in children living in an area of intense malaria transmission.

Thyroglobulin autoantibodies switch to immunoglobulin (Ig)G1 and IgG3 subclasses and preserve their restricted epitope pattern after 131I treatment for Graves' hyperthyroidism: the activity of autoimmune disease influences subclass distribution but not epitope pattern of autoantibodies

PubMed Central

Latrofa, F; Ricci, D; Montanelli, L; Piaggi, P; Mazzi, B; Bianchi, F; Brozzi, F; Santini, P; Fiore, E; Marinò, M; Tonacchera, M; Vitti, P

2014-01-01

The subclass distribution of thyroglobulin autoantibodies (TgAb) is debated, whereas their epitope pattern is restricted. Radioidine (131I) treatment for Graves' disease (GD) induces a rise in TgAb levels, but it is unknown whether it modifies subclass distribution and epitope pattern of TgAb as well. We collected sera from GD patients before 131I treatment and 3 and 6 months thereafter. We measured total TgAb, TgAb light chains and TgAb subclasses by enzyme-linked immunosorbent assay (ELISA) in 25 patients. We characterized the TgAb epitope pattern in 30 patients by inhibiting their binding to 125-ITg by a pool of four TgAb-Fab (recognizing Tg epitope regions A, B, C and D) and to Tg in ELISA by each TgAb-Fab. Total TgAb immunoglobulin (Ig)G rose significantly (P = 0·024). TgAb κ chains did not change (P = 0·052), whereas TgAb λ chains increased significantly (P = 0·001) and persistently. We observed a significant rise in IgG1 and IgG3 levels after 131I (P = 0·008 and P = 0·006, respectively), while IgG2 and IgG4 levels did not change. The rise of IgG1 was persistent, that of IgG3 transient. The levels of inhibition of TgAb binding to Tg by the TgAb-Fab pool were comparable. A slight, non-significant reduction of the inhibition by the immune-dominant TgAb-Fab A was observed 3 and 6 months after 131I. We conclude that 131I treatment for GD increases the levels of the complement-activating IgG1 and IgG3 subclasses and does not influence significantly the epitope pattern of TgAb. In autoimmune thyroid disease subclass distribution of autoantibodies is dynamic in spite of a stable epitope pattern. PMID:25134846

[Human IgG subclass study. II. The levels of the individual IgG subclasses in paired sera from mothers and newborn infants as well as in the blood sera of inhabitants of an isolated northern village].

PubMed

Basova, E N; Stefani, D V; Kazantseva, L Z

1979-07-01

The levels of the first 3 subclasses of IgG, as determined by the radial immunodiffusion test, proved to be similar in the blood sera obtained from mothers and newborns in Moscow. The concentration of IgG4 was 0.64 +/- 0.02 g/l iently indicative of a limited passage of IgG4 molecules through the placenta. The inhabitants of an isolated northern village were found to have the inheritable combined deficit of IfG2 and IgG3 synthesis in their blood sera, which was probably due to the prolonged processes of inbreeding and the progenitor effect.

Immunogenicity and efficacy of a bivalent DNA vaccine containing LeIF and TSA genes against murine cutaneous leishmaniasis.

PubMed

Maspi, Nahid; Ghaffarifar, Fatemeh; Sharifi, Zohreh; Dalimi, Abdolhossein; Dayer, Mohammad Saaid

2017-03-01

There is no effective vaccine for the prevention and elimination of leishmaniasis. For this reason, we assessed the protective effects of DNA vaccines containing LeIF, TSA genes alone, or LeIF-TSA fusion against cutaneous leishmaniasis pEGFP-N1 plasmid (empty vector) and phosphate buffer saline (PBS) were used as control groups. Therefore, cellular and humoral immune responses were evaluated before and after the challenge with Leishmania major. Lesion diameter was also measured 3-12 weeks after challenge. All immunized mice with plasmid DNA encoding Leishmania antigens induced the partial immunity characterized by increased IFN-γ and IgG2a levels compared with control groups (p < 0.001). Furthermore, the immunized mice showed significant reduction in mean lesion sizes compared with mice in empty vector and PBS groups (p < 0.05). The reduction in lesion diameter was 29.3%, 34.1%, and 46.2% less in groups vaccinated with LeIF, TSA, and LeIF-TSA, respectively, than in PBS group at 12th week post infection. IFN/IL-4 and IgG2a/IgG1 ratios indicated that group receiving LeIF-TSA fusion had the highest IFN-γ and IgG2a levels. In this study, DNA immunization promoted Th1 immune response characterized by higher IFN-γ and IgG2a levels and also reduction in lesion size. These results showed that a bivalent vaccine containing two distinct antigens may induce more potent immune responses against leishmaniasis. © 2017 APMIS. Published by John Wiley & Sons Ltd.

Effects of weak/non-complement-binding HLA antibodies on C1q-binding.

PubMed

Hönger, G; Amico, P; Arnold, M-L; Spriewald, B M; Schaub, S

2017-08-01

It is unknown under what conditions and to what extent weak/non-complement (C)-binding IgG subclasses (IgG2/IgG4) can block C1q-binding triggered by C-binding IgG subclasses (IgG1/IgG3). Therefore, we investigated in vitro C1q-binding induced by IgG subclass mixtures targeting the same HLA epitope. Various mixtures of HLA class II specific monoclonal antibodies of different IgG subclasses but identical V-region were incubated with HLA DRB1*07:01 beads and monitored for C1q-binding. The lowest concentration to achieve maximum C1q-binding was measured for IgG3, followed by IgG1, while IgG2 and IgG4 did not show appreciable C1q-binding. C1q-binding occurred only after a critical amount of IgG1/3 has bound and sharply increased thereafter. When both, C-binding and weak/non-C-binding IgG subclasses were mixed, C1q-binding was diminished proportionally to the fraction of IgG2/4. A 2- to 4-fold excess of IgG2/4 inhibited C1q-binding by 50%. Very high levels (10-fold excess) almost completely abrogated C1q-binding even in the presence of significant IgG1/3 levels that would usually lead to strong C1q-binding. In sensitized renal allograft recipients, IgG subclass constellations with ≥ 2-fold excess of IgG2/4 over IgG1/3 were present in 23/66 patients (34.8%) and overall revealed slightly decreased C1q signals. However, spiking of patient sera with IgG2 targeting a different epitope than the patient's IgG1/3 synergistically increased C1q-binding. In conclusion, if targeting the same epitope, an excess of IgG2/4 is repressing the extent of IgG1/3 triggered C1q-binding in vitro. Such IgG subclass constellations are present in about a third of sensitized patients and their net effect on C1q-binding is slightly inhibitory. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

CCR7(lo)PD-1(hi) CXCR5(+) CD4(+) T cells are positively correlated with levels of IL-21 in active and transitional cystic echinococcosis patients.

PubMed

Zhang, Fengbo; Pang, Nannan; Zhu, Yuejie; Zhou, Dexian; Zhao, Hui; Hu, Jinwei; Ma, Xiumin; Li, Jun; Wen, Hao; Samten, Buka; Fan, Haining; Ding, Jianbing

2015-10-26

In our study, we investigated whether circulating T follicular helper (Tfh) and the related cytokines are involved in human cystic echinococcosis (CE). A total of 64 patients with CE and 30 healthy controls were enrolled in this study. Percentages of CCR7(lo)PD-1(hi) cells within CXCR5(+) CD4(+) T cells (circulating Tfh cells) were detected by flow cytometry. Levels of IL-21 and IL-4 in peripheral blood were detected by cytometric bead array. The mRNA expression of IL-21, IL-4, Bcl-6, and Blimp-1 in peripheral blood mononuclear cells (PBMCs) were measured by real-time PCR. Levels of IgG1, IgG2, IgG3, and IgG4 in the patients' sera were measured using enzyme-linked immunosorbent assay. Percentages of circulating Tfh cells were significantly increased in the CE1, CE2, and CE3 groups (p < 0.05). The concentrations of IL-21 and IL-4 in the serum were significantly increased in CE1, CE2, and CE3 groups (p < 0.05). IL-21 was positively correlated with circulating Tfh cells in CE3 group (r = 0.779, p < 0.05). The mRNA levels of IL-21, IL-4, and Bcl-6 were increased in CE1, CE2, and CE3 groups. Levels of IgG1 and IgG4 in patients' sera were increased in CE1, CE2, and CE3 groups. Levels of IgG2 and IgG3 were increased in CE4-5 group. Additionally, after stimulation with hydatid fluid in vitro, the levels of circulating Tfh cells, IL-21 and IL-4 in PBMCs isolated from CE patients were significantly increased (p < 0.05). The levels of circulating Tfh and related cytokines were significantly increased in CE patients, suggesting that they are involved in human CE.

"Checkerboard" assessments of periodontal microbiota and serum antibody responses: a case-control study.

PubMed

Papapanou, P N; Neiderud, A M; Papadimitriou, A; Sandros, J; Dahlén, G

2000-06-01

We explored the association between subgingival microbial profiles and serum IgG responses to periodontal microbiota in relation to clinical periodontal status. One hundred thirty-one (131) periodontitis patients aged 29 to 74 years (mean 51.8) were age- and gender-matched with 74 periodontally intact controls (range 26 to 77, mean 49.3). Smoking habits and health history were recorded and assessments of plaque, bleeding on probing, probing depth, and attachment level were performed at 6 sites per tooth on all present teeth, excluding third molars. Subgingival plaque samples were obtained from each tooth in one upper and one lower quadrant (maximum 14 samples/subject; 2,440 samples total) and analyzed with respect to 19 species by means of whole genomic DNA probes. Serum IgG antibodies against the same 19 species were assessed by an immunoassay. Cases displayed an average of 22.7 teeth, 20.3 sites with probing depth > or =6 mm, and 18.9 sites with attachment loss > or =6 mm. Corresponding figures for controls were 27.1, 0.1, and 1.0, respectively. Heavy smoking was 3 times more frequent among cases than controls (32.1% versus 9.6%). Higher levels of Porphyromonas gingivalis, Porphyromonas endodontalis, Prevotella intermedia, Prevotella nigrescens, Prevotella melaninogenica, Bacteroides forsythus, Fusobacterium nucleatum, Treponema denticola, Eubacterium nodatum, Peptostreptococcus micros, and Campylobacter rectus were found in cases and higher levels of Eikenella corrodens, Veillonella parvula, and Actinomyces naeslundii in controls. Cases displayed higher IgG levels against P. gingivalis and Actinobacillus actinomycetemcomitans, while controls displayed higher levels against F. nucleatum, T. denticola, E. nodatum, and Capnocytophaga ochracea. Positive correlations between bacterial colonization and antibody responses were identified for 9 species in controls. In cases, however, statistically significant correlations were observed for only 3 species out of which only one was positive (V. parvula). Both bacterial levels and antibody responses declined in ages over 55 years. A logistic regression employing selected elements of bacterial colonization and antibody responses as independent variables resulted in 81.1% correct diagnosis, with sensitivity of 83.1%, specificity of 77.8%, positive predictability of 86%, and negative predictability of 73.7%. Smoking did not reach statistical significance in this model. A combined microbial colonization/antibody response profile can effectively discriminate between periodontitis patients and periodontally intact controls.

Serologic Cross-Reactivity of Human IgM and IgG Antibodies to Five Species of Ebola Virus

PubMed Central

MacNeil, Adam; Reed, Zachary; Rollin, Pierre E.

2011-01-01

Five species of Ebola virus (EBOV) have been identified, with nucleotide differences of 30–45% between species. Four of these species have been shown to cause Ebola hemorrhagic fever (EHF) in humans and a fifth species (Reston ebolavirus) is capable of causing a similar disease in non-human primates. While examining potential serologic cross-reactivity between EBOV species is important for diagnostic assays as well as putative vaccines, the nature of cross-reactive antibodies following EBOV infection has not been thoroughly characterized. In order to examine cross-reactivity of human serologic responses to EBOV, we developed antigen preparations for all five EBOV species, and compared serologic responses by IgM capture and IgG enzyme-linked immunosorbent assay (ELISA) in groups of convalescent diagnostic sera from outbreaks in Kikwit, Democratic Republic of Congo (n = 24), Gulu, Uganda (n = 20), Bundibugyo, Uganda (n = 33), and the Philippines (n = 18), which represent outbreaks due to four different EBOV species. For groups of samples from Kikwit, Gulu, and Bundibugyo, some limited IgM cross-reactivity was noted between heterologous sera-antigen pairs, however, IgM responses were largely stronger against autologous antigen. In some instances IgG responses were higher to autologous antigen than heterologous antigen, however, in contrast to IgM responses, we observed strong cross-reactive IgG antibody responses to heterologous antigens among all sets of samples. Finally, we examined autologous IgM and IgG antibody levels, relative to time following EHF onset, and observed early peaking and declining IgM antibody levels (by 80 days) and early development and persistence of IgG antibodies among all samples, implying a consistent pattern of antibody kinetics, regardless of EBOV species. Our findings demonstrate limited cross-reactivity of IgM antibodies to EBOV, however, the stronger tendency for cross-reactive IgG antibody responses can largely circumvent limitations in the utility of heterologous antigen for diagnostic assays and may assist in the development of antibody-mediated vaccines to EBOV. PMID:21666792

Detection of circulating natural antibodies to inflammatory cytokines in type-2 diabetes and clinical significance.

PubMed

Cai, Weiyi; Qiu, Cailing; Zhang, Hongyu; Chen, Xiangyun; Zhang, Xuan; Meng, Qingyong; Wei, Jun

2017-01-01

Inflammatory cytokines have been demonstrated to be involved in developing insulin resistance and type-2 diabetes (T2D). Natural antibodies in the circulation have protective effects on common diseases in humans. The present study was thus designed to test the hypothesis that natural antibodies against inflammatory cytokines could be associated with T2D. An enzyme-linked immunosorbent assay (ELISA) was developed in-house to detect plasma IgG against peptide antigens derived from interleukin 1α (IL1α), IL1β, IL6, IL8 and tumor necrosis factor-α (TNF-α) in 200 patients with T2D and 220 control subjects. Binary regression showed that compared with control subjects, T2D patients had a decreased level of plasma anti-IL6 IgG (adjusted r 2 =0.034, p =0.0001), anti-IL8 IgG (adjusted r 2 =0.021, p =0.002) and anti-TNF-α IgG (adjusted r 2 =0.017, p =0.003). Female patients mainly contributed to decreased levels of anti-IL6 IgG (adjusted r 2 =0.065, p =0.0008) and anti-IL8 IgG (adjusted r 2 =0.056, p =0.003), while male patients mainly contributed to decreased anti-TNF-α IgG levels (adjusted r 2 =0.024, p =0.005). ROC curve analysis revealed a sensitivity of 16.5% against specificity of 95.5% for anti-IL6 IgG assay and a sensitivity of 19.5% against specificity of 95.9% for anti-IL8 IgG assay. Glycated hemoglobin levels measured after 6-month glucose-lowering treatment appeared to be inversely correlated with plasma anti-IL1α IgG ( r =-0.477, df=17, p =0.039) and anti-IL6 IgG ( r =-0.519, df=17, p =0.023) although such correlation failed to survive the Bonferroni correction. Deficiency of natural IgG against inflammatory cytokines is likely to be a risk factor for T2D development and detection of such antibodies may be useful for personalized treatment of the disease.

Altered immune responses in broiler chicken husbandry workers and their association with endotoxin exposure

PubMed Central

GAUTAM, Ravi; HEO, Yong; LIM, GyeongDong; SONG, EunSeob; ROQUE, Katharine; LEE, JaeHee; KIM, YeonGyeong; CHO, AhRang; SHIN, SoJung; KIM, ChangYul; BANG, GiHwan; BAHNG, JiYun; KIM, HyoungAh

2017-01-01

Exposure to bioaerosols in indoor animal farms associates with respiratory illnesses, but little is known about the immune modulation to chicken farmers. This study aimed to compare the general immunity of chicken farmers with those of control subjects with non-agricultural jobs. Blood taken from the farmers and controls was subjected to plasma IgE and IgG subclass measurements. Isolated peripheral blood mononuclear cells (PBMC) were stimulated and cytokine production was measured. Indoor total and respirable dust levels and their endotoxin (LPS) and aflatoxin (AF) levels in the farms were measured. In total, 29 chicken farmers on 19 farms and 14 age- and sex-matched office workers participated. Hematological differences were not observed. The farmers tended to have higher serum IgE and IgG subclass levels with significance for IgG1. The cytokines released by PBMC from farmers indicated skewing toward Type-2 helper T-cell responses: interferon (IFN)-γ:interleukin (IL)-4 and IFNγ:IL-13 ratios were significantly lower than for control PBMC. The farms had 707.1 EU/m3 LPS in total dust, and 15.8 EU/m3 LPS in respirable dust. Farmers exhibited immune skewing towards allergic immune responses that correlated with the LPS levels on their farms. Chicken farmers may be at risk of respiratory allergies due to occupational endotoxin exposure. PMID:28835578

An efficient method to control high mannose and core fucose levels in glycosylated antibody production using deoxymannojirimycin.

PubMed

Shalel Levanon, Sagit; Aharonovitz, Orit; Maor-Shoshani, Ayelet; Abraham, Gita; Kenett, Dan; Aloni, Yehoshua

2018-06-20

Glycosylation on the Fc region of recombinant Immunoglobulin G (IgG) therapeutic antibodies is a critical protein quality attribute which may affect the efficacy and safety of the molecule. During the development of biosimilar therapeutics, adjustment of the glycosylation profile is required in order to match the reference innovator profile. Deoxymannojirimycin (DMJ), a known inhibitor of mannosidase, was used in this study to modulate the glycosylation pattern of antibodies. The effect of DMJ, at concentrations of 5 μM - 500 μM, on non-fucosylated glycoform levels was tested in the biosynthesis processes of two different IgG1 (IgG1 #A and IgG1 #B) using two Chinese hamster ovary (CHO) cell lines (CHO-DXB-11 and CHOK1SV, respectively) in Erlenmeyer flasks and in lab scale bioreactors. DMJ affected glycan forms in a dose response manner. At the highest concentration tested, DMJ reduced N-linked complex glycoform and core fucose levels by 15 and 14 fold, respectively, and increased high mannose level by 21 fold. 10 μM DMJ decreased IgG1 #A core fucose level in CHO-DXB-11 from 92% to 73% and increased high mannose level from 4% to 22% in Erlenmeyer flasks. Furthermore, in lab scale bioreactors, 15 μM DMJ decreased IgG1 #A core fucose level from 95% to 84% and increased high mannose level from 3% to 13%. Core fucose level of IgG1 #B in CHOK1SV was decreased from 81% to 73% using 10 μM DMJ in lab scale bioreactors while high mannose was increased from 6% to 15%. While affecting core fucose and high mannose levels, DMJ decreased maximum viable cell concentration by 16% and did not significantly affect cell productivity (less than 10%). This study demonstrated that DMJ can enable the control of core fucosylated and high mannose levels of IgG1 antibodies in a defined range. Copyright © 2018 Elsevier B.V. All rights reserved.

Anti-erythrocyte antibodies may contribute to anaemia in Plasmodium vivax malaria by decreasing red blood cell deformability and increasing erythrophagocytosis.

PubMed

Mourão, Luiza Carvalho; Roma, Paula Magda da Silva; Sultane Aboobacar, Jamila da Silva; Medeiros, Camila Maia Pantuzzo; de Almeida, Zélia Barbosa; Fontes, Cor Jesus Fernandes; Agero, Ubirajara; de Mesquita, Oscar Nassif; Bemquerer, Marcelo Porto; Braga, Érika Martins

2016-08-04

Plasmodium vivax accounts for the majority of human malaria infections outside Africa and is being increasingly associated in fatal outcomes with anaemia as one of the major complications. One of the causes of malarial anaemia is the augmented removal of circulating non-infected red blood cells (nRBCs), an issue not yet fully understood. High levels of auto-antibodies against RBCs have been associated with severe anaemia and reduced survival of nRBCs in patients with falciparum malaria. Since there are no substantial data about the role of those antibodies in vivax malaria, this study was designed to determine whether or not auto-antibodies against erythrocytes are involved in nRBC clearance. Moreover, the possible immune mechanisms elicited by them that may be associated to induce anaemia in P. vivax infection was investigated. Concentrations of total IgG were determined by sandwich ELISA in sera from clinically well-defined groups of P. vivax-infected patients with or without anaemia and in healthy controls never exposed to malaria, whereas the levels of specific IgG to nRBCs were determined by cell-ELISA. Erythrophagocytosis assay was used to investigate the ability of IgGs purified from each studied pooled sera in enhancing nRBC in vitro clearance by THP-1 macrophages. Defocusing microscopy was employed to measure the biomechanical modifications of individual nRBCs opsonized by IgGs purified from each group. Anaemic patients had higher levels of total and specific anti-RBC antibodies in comparison to the non-anaemic ones. Opsonization with purified IgG from anaemic patients significantly enhanced RBCs in vitro phagocytosis by THP-1 macrophages. Auto-antibodies purified from anaemic patients decreased the nRBC dynamic membrane fluctuations suggesting a possible participation of such antibodies in the perturbation of erythrocyte flexibility and morphology integrity maintenance. These findings revealed that vivax-infected patients with anaemia have increased levels of IgG auto-antibodies against nRBCs and that their deposition on the surface of non-infected erythrocytes decreases their deformability, which, in turn, may enhance nRBC clearance by phagocytes, contributing to the anaemic outcome. These data provide insights into the immune mechanisms associated with vivax malaria anaemia and may be important to the development of new therapy and vaccine strategies.

Characterization of humoral immune responses to chlamydial HSP60, CPAF, and CT795 in inflammatory and severe trachoma.

PubMed

Skwor, Troy; Kandel, Ram Prasad; Basravi, Sunniya; Khan, Aslam; Sharma, Bassant; Dean, Deborah

2010-10-01

Chlamydia trachomatis (Ct) remains the leading global cause of preventable blindness. There are limited data on humoral immune responses in trachoma. Evaluating these responses is important for understanding host-pathogen interactions and informing vaccine design. Antibodies to chlamydial heat shock protein 60 (cHSP60) have been associated with infertility and trachomatous scarring. Other proteins, including chlamydial protease-associated factor (CPAF) and a hypothetical protein unique to the family Chlamydiaceae, CT795, elicit strong immune responses in urogenital infections, but their role in trachomatous disease is unknown. This study was conducted to expand on previous cHSP60 findings and evaluate the association of CPAF and CT795 antibodies with ocular Ct infection and disease. Clinical trachoma grading was performed, and conjunctival samples were obtained from individuals with trachomatous trichiasis (TT; one or more inturned eyelashes) or inflammatory trachoma without trichiasis and control subjects without disease, all of whom resided in trachoma-endemic regions of Nepal. Ct infection was determined using commercial PCR. IgG and IgA tear antibodies against cHSP60, CT795, and CPAF fusion proteins were measured by quantitative ELISA. Significantly higher IgG antibody levels were found against cHSP60, CPAF, and CT795 in the inflammatory cases compared with levels in the controls (P < 0.005 for all three). Ct infection was independently associated with IgG antibodies against all three immunogens in the inflammatory cases but not in the controls (P = 0.025, P = 0.03 and P = 0.017, respectively). Only IgG antibodies against CPAF were significantly elevated among the TT cases (P = 0.013). Among individuals with trachoma, IgG antibody responses to CPAF are likely to be both a marker and risk factor for inflammatory trachoma and severe trachomatous disease.

Levels of salivary immunoglobulins and periodontal evaluation in smoking patients

PubMed Central

2014-01-01

Objective The aim of this study was to assess the level of salivary immunoglobulins and periodontal status in smokers and non-smokers. Materials and methods Unstimulated saliva of 30 subjects (mean age 24.2 ± 3.5 years) who were smokers (test group) and of 30 subjects (mean age 25.3 ± 3.8 years) who were non-smokers (control group) was collected and centrifugated; IgA, IgG, and IgM were measured with the colorimetric immunoenzymatic method. Moreover, the following periodontal clinical parameters were recorded for each subject: plaque index (PI), gingival index (GI), probing depth (PD), and clinical attachment level (CAL). Results A significantly (p< 0.05) lower Ig level was observed in smoking patients (IgA: 20.0 ± 1.2 mg/dl; IgM: 19.5 ± 1.6 mg/dl; IgG: 8.1 ± 1.4 mg/dl) compared to levels in the non-smoking control group (IgA: 234.1 ± 65.2 mg/dl; IgM: 121.0 ± 31.7 mg/dl; IgG: 1049.4 ± 102 mg/dl). In the test group, PI (2.2 ± 0.3), GI (2.4 ±0.5), PD (49.3 ± 9.2%), and CAL (49.3 ± 4.6%) were higher (p< 0.05) than those observed in the control group (PI: 0.8 ± 0.4; GI: 0.7 ± 0.3; PD: 10.6 ± 2.4%; CAL: 3.1 ± 0.8%). Conclusion Smoking subjects showed lower levels of salivary IgA, IgG, and IgM and a worse periodontal condition than non-smoking subjects. On the base of our study, as smoking subjects also had lower levels of IgA, IgG, and IgM in their saliva than non-smoking subjects, despite the fact that there is little evidence that the salivary Igs have a protective action against periodontitis and that the whole saliva does not result in whole from the salivary glands, it can be concluded that the deteriorated periodontal health conditions of these patients can be attributed in part to a lowering of the host’s defense due to a decrease in the quantity of Igs in salivary fluid. PMID:24502245

Pre-immunotherapy serum CA27.29 (MUC-1) mucin level and CD69+ lymphocytes correlate with effects of Theratope sialyl-Tn-KLH cancer vaccine in active specific immunotherapy.

PubMed

Reddish, M A; MacLean, G D; Poppema, S; Berg, A; Longenecker, B M

1996-06-01

Patients with metastatic breast, colorectal or ovarian cancers received active specific immunotherapy (ASI) with Theratope sialyl-Tn-KLH (keyhole limpet hemocyanin) cancer vaccine emulsified in Detox adjuvant. The median log2 anti-STn IgG titer generated by ASI, estimated by enzyme-linked immunosorbent assay with solid-phase ovine submaxillary mucin, was 5.322 (range = 0 - 9.322). Following ASI, 51 patients who generated titers higher than the median value for anti-STn+ mucin IgG survived longer than 46 patients who generated lower titers below the median. 38 of the patients were phenotyped for CD69 prior to ASI. The patients with lower numbers of CD69+ peripheral blood lymphocytes prior to immunotherapy (pre-ASI) also had low serum CA27.29 cancer antigen (MUC-1) levels, and had longer times to disease progression and improved survival following ASI. Elevated pre-ASI serum CA27.29 tumor antigen levels were associated with higher numbers of CD69+ PBL, with decreased anti-STn antibody production and decreased survival following ASI. The data are compatible with the hypothesis that elevated serum MUC-1 mucin is specifically immunosuppressive.

Adjuvant activity of peptidoglycan monomer and its metabolic products.

PubMed

Halassy, Beata; Krstanović, Marina; Frkanec, Ruza; Tomasić, Jelka

2003-02-14

Peptidoglycan monomer (PGM) is a natural compound of bacterial origin. It is a non-toxic, non-pyrogenic, water-soluble immunostimulator potentiating humoral immune response to ovalbumin (OVA) in mice. It is fast degraded and its metabolic products-the pentapeptide (PP) and the disaccharide (DS)-are excreted from the mammalian organism upon parenteral administration. The present study investigates: (a). whether PGM could influence the long-living memory generation; (b). whether metabolic products retain adjuvant properties of the parent compound and contribute to its adjuvanticity. We report now that mice immunised twice with OVA+PGM had significantly higher anti-OVA IgG levels upon challenge with antigen alone 6 months later in comparison to control group immunised with OVA only. PP and DS were prepared enzymatically in vitro as apyrogenic and chemically pure compounds. When mice were immunised with OVA plus PP and DS, respectively, the level of anti-OVA IgGs in sera was not higher than in mice immunised with OVA alone, while PGM raised the level of specific antibodies. Results implicate that the adjuvant active molecule, capable of enhancing long-living memory generation, is PGM itself, and none of its metabolic products.

Serologic Tests of IgG and IgM Antibodies and IgG Avidity for Diagnosis of Ocular Toxoplasmosis.

PubMed

Rahimi-Esboei, Bahman; Zarei, Mohammad; Mohebali, Mehdi; Valian, Hossein Keshavarz; Shojaee, Saeedeh; Mahmoudzadeh, Raziyeh; Salabati, Mirataollah

2018-04-01

This prospective study was aimed to detect acute and chronic ocular toxoplasmosis by comparison of anti- Toxoplasma gondii IgM and IgG antibody levels and IgG avidity test. One hundred and seventeen patients with ocular toxoplasmosis (OT) who referred to the Farabi Eye Hospital, Tehran, Iran were included in this study. Of the patients, 77 cases were positive for anti- T. gondii IgG, and 8 cases were positive for anti- T. gondii IgM. IgG avidity test revealed 11, 4, and 102 cases were low, intermediate, and high, respectively, and 6.8% and 9.4% of cases were positive for IgM and IgG avidity tests, respectively ( P =0.632). Agreement (Kappa value) between paired tests IgG-IgM, IgG-IgG avidity, and IgM-IgG avidity was 0.080, 0.099, and 0.721, respectively ( P <0.05). This study showed that conventional serologic tests (IgM and IgG levels) and IgG avidity correlate well each other and can be used to differentiate recent infections from old OT. It seems that reactivated old infections rather than recently acquired infections are majority of Iranian OT patients.

Overlapping Morphologic and Immunohistochemical Features of Hashimoto Thyroiditis and IgG4-Related Thyroid Disease.

PubMed

Raess, Philipp W; Habashi, Arlette; El Rassi, Edward; Milas, Mira; Sauer, David A; Troxell, Megan L

2015-05-01

Immunoglobulin G4-related disease (IgG4-RD) is an emerging clinicopathologic entity characterized by both IgG4+ plasma cell infiltration and fibrosis in one or more organs, prototypically pancreas or salivary/lacrimal glands. IgG4-RD in the thyroid (IgG4-RTD) is an area of active study, and the relationship between IgG4-RTD and Hashimoto thyroiditis is not fully delineated due to their overlapping histologic features. Retrospective review was performed of all thyroidectomy cases demonstrating lymphocytic inflammation at a single institution over a 4-year period. Approximately half (23/38) of patients had a clinical diagnosis of Hashimoto thyroiditis (HT). Nine of the 38 patients had increased absolute and relative numbers of IgG4+ plasma cells. Patients with a clinical diagnosis of HT had increased lymphoplasmacytic inflammation, but the relative proportion of IgG4+ plasma cells was not increased compared to patients without HT. There was no correlation between IgG4 levels and the amount of fibrosis in patients with or without HT. Patients identified as having the fibrosing variant of HT were not more likely to have increased levels of IgG4+ plasma cells than those without. There is significant morphologic and immunohistochemical overlap between HT and IgG4-RTD. Future studies to identify specific characteristics of IgG4-RTD involving the thyroid are necessary to accurately define this entity.

Anti-dengue virus envelope protein domain III IgG ELISA among infants with primary dengue virus infections.

PubMed

Libraty, Daniel H; Zhang, Lei; Obcena, AnaMae; Brion, Job D; Capeding, Rosario Z

2015-02-01

Dengue is the most prevalent arthropod-borne viral illness in humans. The current gold standard serologic test for dengue virus (DENV) infection is a neutralizing antibody assay. We examined a DENV recombinant (r)E protein domain III IgG ELISA among infants with primary DENV infections. Infants experience a primary DENV infection in the presence of maternally derived anti-DENV IgG. The estimated DENV rE protein domain III IgG levels to the infecting serotype at the time of infant primary symptomatic DENV2 and DENV3 infections correlated with the 50% plaque reduction neutralization reciprocal antibody titers (PRNT50). Anti-DENVs 1-4 rE protein domain III IgG levels all correlated with each other, and the estimated rE protein domain III IgG level to the infecting serotype at the time of infection inversely correlated with dengue disease severity. The anti-DENV rE protein domain III IgG ELISA may be a useful and potentially high-throughput alternative to traditional DENV neutralizing antibody assays. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

The Use of Xanthan Gum as Vaccine Adjuvant: An Evaluation of Immunostimulatory Potential in BALB/c Mice and Cytotoxicity In Vitro

PubMed Central

Oliveira, Thaís Larré; Collares, Thaís Farias; Monte, Leonardo Garcia; Inda, Guilherme Roig; Moreira, Angelita da Silveira

2017-01-01

The successful production of new, safe, and effective vaccines that generate immunological memory is directly related to adjuvant feature, which is responsible for increasing and/or modulating the immune response. Several compounds display adjuvant activity, including carbohydrates. These compounds play important roles in the immune response, as well as having biocompatible properties in vaccine formulations. One such carbohydrate is xanthan gum, a polysaccharide that is produced by the plant-pathogenic bacterium Xanthomonas spp., which has adjuvant attributes. This study evaluated the immune response induced by xanthan gum associated with ovalbumin in BALB/c mice, which were subcutaneously immunized, in terms of antibody production (IgG1, IgG2a, IgG2b, and IgG3), and assessed the levels of IFN-γ in the splenocyte culture using indirect ELISA. Furthermore, we investigated in vitro cytotoxicity of xanthan in the embryo fibroblasts cell line of the NIH/3T3 mouse by MTT assay and propidium iodide uptake assay. The mice immunized with ovalbumin plus xanthan gum exhibited higher antibody IgG1 responses than control groups. Furthermore, the xanthan polysaccharide was capable of increasing the immunogenicity of antigens by producing IFN-γ and did not exhibit cytotoxicity effects in NIH/3T3 mouse fibroblast cells, considered a promising candidate for vaccine adjuvant. PMID:28555192

Cysteine Racemization on IgG Heavy and Light Chains

PubMed Central

Zhang, Qingchun; Flynn, Gregory C.

2013-01-01

Under basic pH conditions, the heavy chain 220-light chain 214 (H220-L214) disulfide bond, found in the flexible hinge region of an IgG1, can convert to a thioether. Similar conditions also result in racemization of the H220 cysteine. Here, we report that racemization occurs on both H220 and L214 on an IgG1 with a λ light chain (IgG1λ) but almost entirely on H220 of an IgGl with a κ light chain (IgG1κ) under similar conditions. Likewise, racemization was detected at significant levels on H220 and L214 on endogenous human IgG1λ but only at the H220 position on IgG1κ. Low but measurable levels of d-cysteines were found on IgG2 cysteines in the hinge region, both with monoclonal antibodies incubated under basic pH conditions and on antibodies isolated from human serum. A simplified reaction mechanism involving reversible β-elimination on the cysteine is presented that accounts for both base-catalyzed racemization and thioether formation at the hinge disulfide. PMID:24142697

Timothy-specific IgG antibody levels vary with the pollen seasons.

PubMed

Nordvall, S L; Larsson, P H; Johansson, S G

1986-11-01

Serum samples were collected from eight grass pollen hypersensitive children during a 4-year period. The sera were assayed for contents of timothy-specific IgE antibodies by RAST. Timothy-specific IgG and IgA antibodies were quantified by a refined ELISA in which covalent binding of the antigen to the polystyrene solid phase had been performed. IgG antibodies were also assayed by a Sepharose-protein-A technique with radiolabelled timothy allergens as the antigen. It was possible to register clearcut seasonal variations with postseasonally boosted antibody levels not only of timothy-specific IgE but also of IgG antibody. Both IgG1 and IgG4 antibodies specific for timothy showed seasonal variations of a similar degree. It was not possible to register seasonal variations of the same magnitude of timothy-specific IgA antibodies.

Re-examination of immune response and estimation of anti-Vi IgG protective threshold against typhoid fever-based on the efficacy trial of Vi conjugate in young children.

PubMed

Szu, Shousun C; Klugman, Keith P; Hunt, Steven

2014-04-25

The capsular polysaccharide of Salmonella enterica serovar Typhi, Vi antigen, is an essential virulence factor and a protective antigen. Similar to other polysaccharide vaccines, the protective action of Vi, both to the polysaccharide alone or when presented as a conjugate, is mediated by serum IgG Vi antibodies. The evaluation of Vi capsular polysaccharide based vaccines to prevent typhoid fever would be significantly facilitated by the identification of a "protective level" of serum antibodies to Vi antigen. The protective level of anti-Vi IgG against typhoid fever was derived from the protective efficacy and immune response of a Vi-rEPA conjugate vaccine efficacy trial. The estimation was derived by two methods: correlation of the percent efficacy and the antibody distribution profile in the vaccine group at a given period of observation, and use of the relative ratio of anti-Vi IgG levels between the vaccine and placebo groups greater or equal to the Relative Risk of typhoid fever used in the efficacy determination. Both methods predicted a similar range of a minimum protective level of anti-Vi IgG between 1.4 and 2.0μg/ml (short term threshold). When applying a protective threshold of 10μg/ml at 6 months post immunization, an IgG level in excess of 1.4μg/ml was achieved by 90% of children at 46 months post immunization, consistent with an 89% level of protection over the duration of the study. We thus suggest that the proportion of children with Vi IgG>10μg/ml (long term threshold) 6 months after immunization may reflect the proportion protected over at least a 4 year period. The current assignment of an anti-Vi IgG protective level may be of value when evaluating vaccine performance of future Vi conjugate vaccines. Published by Elsevier Ltd.

Polymer-mediated immunocamouflage of red blood cells: effects of polymer size on antigenic and immunogenic recognition of allogeneic donor blood cells.

PubMed

Wang, DunCheng; Kyluik, Dana L; Murad, Kari L; Toyofuku, Wendy M; Scott, Mark D

2011-07-01

Developing a practical means of reducing alloimmunization in chronically transfused patients would be of significant clinical benefit. Immunocamouflaging red blood cells (RBCs) by membrane grafting of methoxypoly(ethylene glycol) (mPEG) may reduce the risk of allo-immunization. The results of this study showed that antibody recognition of non-ABO antigens was significantly reduced in an mPEG-dose- and polymer size-dependent manner, with higher molecular weight mPEGs providing better immunoprotection. Furthermore, in vivo immunogenicity was significantly reduced in mice serially transfused with mPEG-modified xenogeneic (sheep; sRBCs), allogeneic (C57Bl/6), or syngeneic (Balb/c) RBCs. Following a primary transfusion of sRBCs, mice receiving mPEG-sRBCs showed a >90% reduction in anti-sRBC IgG antibody levels. After two transfusions, mice receiving mPEG-sRBCs showed reductions of >80% in anti-sRBC IgG levels. Importantly, mPEG-modified autologous cells did not induce neoantigens or an immune (IgG or IgM) response. These data suggest that the global immunocamouflage of RBCs by polymer grafting may provide a safe and cost-effective means of reducing the risk of alloimmunization.

PD-1HIGH Follicular CD4 T Helper Cell Subsets Residing in Lymph Node Germinal Centers Correlate with B Cell Maturation and IgG Production in Rhesus Macaques

PubMed Central

Xu, Huanbin; Wang, Xiaolei; Lackner, Andrew A.; Veazey, Ronald S.

2014-01-01

CD4+ T follicular helper (TFH) cells guide development and maturation of B cells and are crucial for effective antibody responses. Here we found rhesus macaque TFH cells, defined as CXCR5+CD4 T cells, contain two major populations: PD-1INT and PD-1HIGH cells. Of these, PD-1HIGHCD4+ T cells highly co-express ICOS but little CCR7, and reside in lymph node germinal centers (GCs), but not in blood. These cells secrete IL-21 and express transcriptional factor Bcl-6 at higher levels than CXCR5+PD-1INTCD4+ T cells. In addition, the frequency of PD-1HIGHCD4+ T cells is low in lymph nodes of newborns, but increases with age. Levels of PD-1HIGHCD4+ T cells correlate with mature B cells in lymph nodes, and PD-1 blockade in PD-1HIGHCD4+ T and B cell co-cultures significantly inhibits IgG production. In summary, PD-1HIGHCD4+ T cells residing in GC represent a specific TFH subset that contributes to maturation of B cells and IgG production. PMID:24678309

Enhancement of immunogenic response and protection in model rats by CSTM nanoparticles anticaries DNA vaccine.

PubMed

Li, Hongjiao; Lu, Yiming; Xiang, Jingjie; Jiang, Hailong; Zhong, Yanqiang; Lu, Ying

2016-06-01

To construct anticaries DNA vaccine and evaluate its ability to elicit mucosal and systemic immune responses in rats. wapA fragment was cloned into pVAX1 plasmid to generate pVAX1-wapA. The pVAX1-wapA/trimethyl chitosan nanoparticles were prepared by complex coacervation method. Significantly higher specific IgG antibody titers were observed in rats immunized with nanoparticles compared with rats immunized with naked pVAX1-wapA. Anti-WapA IgA and IgG antibody levels after intranasal immunization were significantly higher than those following intramuscular delivery of nanoparticles or naked pVAX1-wapA. Furthermore, fewer enamel, slight dentin and dentin moderate lesions were observed in rats immunized with nanoparticles. The results implicate WapA as an excellent candidate for anticaries vaccine development and nanoparticles as an effective delivery system.

Ventricular assist device elicits serum natural IgG that correlates with the development of primary graft dysfunction following heart transplantation.

PubMed

See, Sarah B; Clerkin, Kevin J; Kennel, Peter J; Zhang, Feifan; Weber, Matthew P; Rogers, Kortney J; Chatterjee, Debanjana; Vasilescu, Elena R; Vlad, George; Naka, Yoshifumi; Restaino, Susan W; Farr, Maryjane A; Topkara, Veli K; Colombo, Paolo C; Mancini, Donna M; Schulze, P Christian; Levin, Bruce; Zorn, Emmanuel

2017-08-01

Pre-transplant sensitization is a limiting factor in solid-organ transplantation. In heart transplants, ventricular assist device (VAD) implantation has been associated with sensitization to human leukocyte antigens (HLA). The effect of VAD on non-HLA antibodies is unclear. We have previously shown that polyreactive natural antibodies (Nabs) contribute to pre-sensitization in kidney allograft recipients. Here we assessed generation of Nabs after VAD implantation in pre-transplant sera and examined their contribution to cardiac allograft outcome. IgM and IgG Nabs were tested in pre-transplant serum samples collected from 206 orthotopic heart transplant recipients, including 128 patients with VAD (VAD patients) and 78 patients without VAD (no-VAD patients). Nabs were assessed by testing serum reactivity to apoptotic cells by flow cytometry and to the generic oxidized epitope, malondialdehyde, by enzyme-linked immunosorbent assay. No difference was observed in serum levels of IgM Nabs between VAD and no-VAD patients. However, serum IgG Nabs levels were significantly increased in VAD compared with no-VAD patients. This increase was likely due to the presence of the VAD, as revealed by lower serum IgG Nabs levels before implantation. Elevated pre-transplant IgG Nabs level was associated with development of primary graft dysfunction (PGD). Our study demonstrates that VAD support elicits IgG Nabs reactive to apoptotic cells and oxidized epitopes. These findings further support broad and non-specific B-cell activation by VAD, resulting in IgG sensitization. Moreover, the association of serum IgG Nabs levels with development of PGD suggests a possible role for these antibodies in the inflammatory reaction accompanying this complication. Copyright © 2017 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Incidence of Severe Malaria Syndromes and Status of Immune Responses among Khat Chewer Malaria Patients in Ethiopia

PubMed Central

Ketema, Tsige

2015-01-01

Although more emphasis has been given to the genetic and environmental factors that determine host vulnerability to malaria, other factors that might have a crucial role in burdening the disease have not been evaluated yet. Therefore, this study was designed to assess the effect of khat chewing on the incidence of severe malaria syndromes and immune responses during malaria infection in an area where the two problems co-exist. Clinical, physical, demographic, hematological, biochemical and immunological data were collected from Plasmodium falciparum mono-infected malaria patients (age ≥ 10 years) seeking medication in Halaba Kulito and Jimma Health Centers. In addition, incidences of severe malaria symptoms were assessed. The data were analyzed using SPSS (version 20) software. Prevalence of current khat chewer malaria patients was 57.38% (95%CI =53-61.56%). Malaria symptoms such as hyperpyrexia, prostration and hyperparasitemia were significantly lower (P<0.05) among khat chewer malaria patients. However, relative risk to jaundice and renal failure were significantly higher (P<0.05) in khat chewers than in non-khat chewer malaria patients. Longer duration of khat use was positively associated with incidence of anemia. IgM and IgG antibody titers were significantly higher (P<0.05) among khat chewer malaria patients than among malaria positive non-chewers. Although levels of IgG subclasses in malaria patients did not show significant differences (P>0.05), IgG3 antibody was significantly higher (P<0.001) among khat chewer malaria patients. Moreover, IgM, IgG, IgG1and IgG3 antibodies had significant negative association (P<0.001) with parasite burden and clinical manifestations of severe malaria symptoms, but not with severe anemia and hypoglycemia. Additionally, a significant increment (P<0.05) in CD4+ T-lymphocyte population was observed among khat users. Khat might be an important risk factor for incidence of some severe malaria complications. Nevertheless, it can enhance induction of humoral immune response and CD4+ T-lymphocyte population during malaria infection. This calls for further investigation on the effect of khat on parasite or antigen-specifc protective malaria immunity and analysis of cytokines released upon malaria infection among khat chewers. PMID:26173100

[IgG(4)-related disease involving the trachea and paratracheal soft tissue: a case report and literature review].

PubMed

Fang, W L; Wang, H J; Lu, Y W; Feng, R E; Bu, X N; Fang, Q H

2017-03-01

Objective: To investigate the clinical data of a patient with IgG(4)-related disease involving the trachea and paratracheal soft tissue and review the literature so as to improve the understanding level of the disorder. Methods: To analyze the clinical manifestation, laboratory examination, imaging, histopathology, treatment and prognosis of a patient with IgG(4)-related disease trachea and paratracheal soft tissue involved, who was admitted to the Department of Respiratory and Critical Care Medicine at Beijing Chaoyang Hospital. The relevant literatures were reviewed. Results: A 18-year-old female was admitted with chief complaint of cough, dyspnea, and neck mass. Neck CT suggested that tracheal stenosis was caused by surrounded soft tissue. Paratracheal mass biopsy showed dense collagen fibers with infiltration of many lymphocytes and plasma cells. Immunohistochemical stain found that IgG(4)-positive plasma cells were >50/high power field (HPF) and a ratio of IgG(4)/IgG positive cells was over 40% .The level of serum IgG(4) was significantly increased (2 930 mg/L). She was diagnosed as IgG(4)-related disease. The patient was treated with 80 mg intravenous methylprednisolone per day for three days, then prednisone 40 mg daily oral. Her dyspnea was significantly relieved.One month later, CT scan showed that the cervical tracheal stenosis was significantly improved. We identified 20 cases of IgG(4)-related disease involving the trachea and paratracheal soft tissue from databases, in which only 1 case was similar as this patient. The other 19 cases were of extratracheal involvement. Elevated serum IgG(4) was detected in 11/12 patients. Most patients were treated with glucocorticoid, some combined with immunosuppressive agents and rituximab. The clinical outcome was good. Conclusion: IgG(4)-related disease involving the trachea and paratracheal soft tissue is a rare condition. Serum IgG(4) level and histopathology should be considered for diagnosis. Glucocorticoid is effective.

Comparative Assessment of Induced Immune Responses Following Intramuscular Immunization with Fusion and Cocktail of LeIF, LACK and TSA Genes Against Cutaneous Leishmaniasis in BALB/c Mice.

PubMed

Maspi, Nahid; Ghaffarifar, Fatemeh; Sharifi, Zohreh; Dalimi, Abdolhossein; Dayer, Mohammad Saaid

2018-02-01

In the present study, we evaluated induced immune responses following DNA vaccine containing cocktail or fusion of LeIF, LACK and TSA genes or each gene alone. Mice were injected with 100 µg of each plasmid containing the gene of insert, plasmid DNA alone as the first control group or phosphate buffer saline as the second control group. Then, cellular and humoral responses, lesion size were measured for all groups. All vaccinated mice induced Th1 immune responses against Leishmania characterized by higher IFN-γ and IgG2a levels compared with control groups (p < 0.05). In addition, IFN-γ levels increased in groups immunized with fusion and cocktail vaccines in comparison with LACK (p < 0.001) and LeIF (p < 0.01) groups after challenge. In addition, fusion and cocktail groups produced higher IgG2a values than groups vaccinated with a gene alone (p < 0.05). Lesion progression delayed for all immunized groups compared with control groups from 5th week post-infection (p < 0.05). Mean lesion size decreased in immunized mice with fusion DNA than three groups vaccinated with one gene alone (p < 0.05). While, lesion size decreased significantly in cocktail recipient group than LeIF recipient group (p < 0.05). There was no difference in lesion size between fusion and cocktail groups. Overall, immunized mice with cocktail and fusion vaccines showed stronger Th1 response by production of higher IFN-γ and IgG2a and showed smaller mean lesion size. Therefore, use of multiple antigens can improve induced immune responses by DNA vaccination.

Gut barrier failure biomarkers are associated with poor disease outcome in patients with primary sclerosing cholangitis

PubMed Central

Tornai, Tamas; Palyu, Eszter; Vitalis, Zsuzsanna; Tornai, Istvan; Tornai, David; Antal-Szalmas, Peter; Norman, Gary L; Shums, Zakera; Veres, Gabor; Dezsofi, Antal; Par, Gabriella; Par, Alajos; Orosz, Peter; Szalay, Ferenc; Lakatos, Peter Laszlo; Papp, Maria

2017-01-01

AIM To assess the prevalence of a panel of serologic markers that reflect gut barrier dysfunction in a mixed cohort of pediatric and adult primary sclerosing cholangitis (PSC) patients. METHODS Sera of 67 PSC patients [median age (range): 32 (5-79) years, concomitant IBD: 67% and cirrhosis: 20%] were assayed for the presence of antibodies against to F-actin (AAA IgA/IgG) and gliadin (AGA IgA/IgG)] and for serum level of intestinal fatty acid-binding protein (I-FABP) by ELISA. Markers of lipopolysaccharide (LPS) exposure [LPS binding protein (LBP)] and various anti-microbial antibodies [anti-OMP Plus IgA and endotoxin core IgA antibody (EndoCAb)] were also determined. Poor disease outcome was defined as orthotopic liver transplantation and/or liver-related death during the follow-up [median: 99 (14-106) mo]. One hundred and fifty-three healthy subjects (HCONT) and 172 ulcerative colitis (UC) patients were the controls. RESULTS A total of 28.4%, 28.0%, 9% and 20.9% of PSC patients were positive for AAA IgA, AAA IgG, AGA IgA and AGA IgG, respectively. Frequencies of AAA IgA and AAA IgG (P < 0.001, for both) and AGA IgG (P = 0.01, for both) but not AGA IgA were significantly higher compared to both of the HCONT and the UC groups. In survival analysis, AAA IgA-positivity was revealed as an independent predictor of poor disease outcome after adjusting either for the presence of cirrhosis [HR = 5.15 (1.27-20.86), P = 0.022 or for the Mayo risk score (HR = 4.24 (0.99-18.21), P = 0.052]. AAA IgA-positivity was significantly associated with higher frequency of anti-microbial antibodies (P < 0.001 for EndoCab IgA and P = 0.012 for anti-OMP Plus IgA) and higher level of the enterocyte damage marker (median I-FABPAAA IgA pos vs neg: 365 vs 166 pg/mL, P = 0.011), but not with serum LBP level. CONCLUSION Presence of IgA type AAA identified PSC patients with progressive disease. Moreover, it is associated with enhanced mucosal immune response to various microbial antigens and enterocyte damage further highlighting the importance of the gut-liver interaction in PSC. PMID:28839442

Evaluation of treatment of colostrum-deprived kittens with equine IgG.

PubMed

Crawford, P Cynda; Hanel, Rita M; Levy, Julie K

2003-08-01

To evaluate equine IgG as a treatment for kittens with failure of passive transfer of immunity (FPT). 13 specific pathogen-free queens and their 77 kittens. Kittens were randomized at birth into 9 treatment groups. One group contained colostrum-fed (nursing) kittens; the other groups contained colostrum-deprived kittens that were administered supplemental feline or equine IgG PO or SC during the first 12 hours after birth. Blood samples were collected at serial time points from birth to 56 days of age for determination of serum IgG concentrations. The capacity of equine IgG to opsonize bacteria for phagocytosis by feline neutrophils was determined via flow cytometry. Kittens that received feline or equine IgG SC had significantly higher serum IgG concentrations than those of kittens that received the supplements PO. In kittens that were administered supplemental IgG SC, serum IgG concentrations were considered adequate for protection against infection. The half-life of IgG in kittens treated with equine IgG was shorter than that in kittens treated with feline IgG. Feline IgG significantly enhanced the phagocytosis of bacteria by feline neutrophils, but equine IgG did not. Serum concentrations of equine IgG that are considered protective against infection are easily attained in kittens, but the failure of these antibodies to promote bacterial phagocytosis in vitro suggests that equine IgG may be an inappropriate treatment for FPT in kittens.

P. falciparum infection and maternofetal antibody transfer in malaria-endemic settings of varying transmission

PubMed Central

Stanisic, Danielle; McGready, Rose; Chotivanich, Kesinee; Clapham, Caroline; Baiwog, Francesca; Pimanpanarak, Mupawjay; Siba, Peter; Mueller, Ivo; King, Christopher L.; Nosten, François; Beeson, James G.; Rogerson, Stephen; Simpson, Julie A.; Fowkes, Freya J. I.

2017-01-01

Introduction During pregnancy, immunoglobulin G (IgG) is transferred from the mother to the fetus, providing protection from disease in early infancy. Plasmodium falciparum infections may reduce maternofetal antibody transfer efficiency, but mechanisms remain unclear. Methods Mother-cord paired serum samples collected at delivery from Papua New Guinea (PNG) and the Thailand-Myanmar Border Area (TMBA) were tested for IgG1 and IgG3 to four P. falciparum antigens and measles antigen, as well as total serum IgG. Multivariable linear regression was conducted to assess the association of peripheral P. falciparum infection during pregnancy or placental P. falciparum infection assessed at delivery with maternofetal antibody transfer efficiency. Path analysis assessed the extent to which associations between P. falciparum infection and antibody transfer were mediated by gestational age at delivery or levels of maternal total serum IgG. Results Maternofetal antibody transfer efficiency of IgG1 and IgG3 was lower in PNG compared to TMBA (mean difference in cord antibody levels (controlling for maternal antibody levels) ranged from -0.88 to 0.09, median of -0.20 log2 units). Placental P. falciparum infections were associated with substantially lower maternofetal antibody transfer efficiency in PNG primigravid women (mean difference in cord antibody levels (controlling for maternal antibody levels) ranged from -0.62 to -0.10, median of -0.36 log2 units), but not multigravid women. The lower antibody transfer efficiency amongst primigravid women with placental infection was only partially mediated by gestational age at delivery (proportion indirect effect ranged from 0% to 18%), whereas no mediation effects of maternal total serum IgG were observed. Discussion Primigravid women may be at risk of impaired maternofetal antibody transport with placental P. falciparum infection. Direct effects of P. falciparum on the placenta, rather than earlier gestational age and elevated serum IgG, are likely responsible for the majority of the reduction in maternofetal antibody transfer efficiency with placental infection. PMID:29028827

P. falciparum infection and maternofetal antibody transfer in malaria-endemic settings of varying transmission.

PubMed

McLean, Alistair R D; Stanisic, Danielle; McGready, Rose; Chotivanich, Kesinee; Clapham, Caroline; Baiwog, Francesca; Pimanpanarak, Mupawjay; Siba, Peter; Mueller, Ivo; King, Christopher L; Nosten, François; Beeson, James G; Rogerson, Stephen; Simpson, Julie A; Fowkes, Freya J I

2017-01-01

During pregnancy, immunoglobulin G (IgG) is transferred from the mother to the fetus, providing protection from disease in early infancy. Plasmodium falciparum infections may reduce maternofetal antibody transfer efficiency, but mechanisms remain unclear. Mother-cord paired serum samples collected at delivery from Papua New Guinea (PNG) and the Thailand-Myanmar Border Area (TMBA) were tested for IgG1 and IgG3 to four P. falciparum antigens and measles antigen, as well as total serum IgG. Multivariable linear regression was conducted to assess the association of peripheral P. falciparum infection during pregnancy or placental P. falciparum infection assessed at delivery with maternofetal antibody transfer efficiency. Path analysis assessed the extent to which associations between P. falciparum infection and antibody transfer were mediated by gestational age at delivery or levels of maternal total serum IgG. Maternofetal antibody transfer efficiency of IgG1 and IgG3 was lower in PNG compared to TMBA (mean difference in cord antibody levels (controlling for maternal antibody levels) ranged from -0.88 to 0.09, median of -0.20 log2 units). Placental P. falciparum infections were associated with substantially lower maternofetal antibody transfer efficiency in PNG primigravid women (mean difference in cord antibody levels (controlling for maternal antibody levels) ranged from -0.62 to -0.10, median of -0.36 log2 units), but not multigravid women. The lower antibody transfer efficiency amongst primigravid women with placental infection was only partially mediated by gestational age at delivery (proportion indirect effect ranged from 0% to 18%), whereas no mediation effects of maternal total serum IgG were observed. Primigravid women may be at risk of impaired maternofetal antibody transport with placental P. falciparum infection. Direct effects of P. falciparum on the placenta, rather than earlier gestational age and elevated serum IgG, are likely responsible for the majority of the reduction in maternofetal antibody transfer efficiency with placental infection.

Determination of antibody to Streptococcus mutans from radiation-induced xerostomia patients. Agglutination activity against cariogenic microorganisms, active immunoglobulin classes, and post-irradiation caries activity in cancer patients. Final report 15 jul 77-14 apr 79

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brown, L.R.; O'Neill, P.A.; Dreizen, S.

1979-07-01

The relationship between specific agglutination (Ag) and caries activity during 30 month post radiation was assessed in 36 head and neck cancer patients. Ag titers in 444 saliva and 481 serum samples from these patients and 16 noncancer controls were determined against formalinized cellular antigens of Streptococcus mutans (Sm), Streptococcus sanguis (Ss), Streptococcus mitis, Lactobacillus fermenti (Lf), and Lactobacillus casei. Saliva IgA and IgG levels and Ag titers were significantly higher in cancer patients than in noncancer controls. Post radiation-induced xerostomic changes in saliva IgA reflected changes in specific Ag against oral microbes, particularly Sm serotype c. Patients with highmore » saliva IgA levels had significantly higher saliva Ag titers to Sm, Ss and Lf, lower plaque Sm counts and lower caries activity than patients with low saliva IgA levels. Serum Ag titers, however, showed no significant relationship with either serum Ig levels, microbial counts or caries activity. Chromatographic separation of Ig classes showed that Ag activity in saliva stemmed mainly from secretory IgA. Most serum Ag activity was found in regions corresponding to IgG and 7S IgA.« less

Immunoglobulin G levels during collection of large volume plasma for fractionation.

PubMed

Burkhardt, Thomas; Rothe, Remo; Moog, Rainer

2017-06-01

There is a need of comprehensive work dealing with the quality of plasma for fractionation with respect to the IgG content as today most plasma derivates are used to treat patients with immunodeficiencies and autoimmune disorders. Therefore, a prospective study was carried out to analyse IgG levels before plasmapheresis and every 200ml collected plasma. Fifty-four experienced plasmapheresis donors were recruited for subsequent 850ml plasmapheresis using the Aurora Plasmapheresis System. Donorś peripheral blood counts were analysed before and after plasmapheresis using an electronic counter. Total protein, IgG and citrate were measured turbidometrically before, during and after apheresis as well as in the plasma product. Furthermore, platelets, red and white blood cells were analysed as parameters of product quality. An average of 2751±247ml blood was processed in 47±6min. The collected plasma volume was 850±1mL and citrate consumption was 177±15mL. A continuous drop of donors' IgG level was observed during plasmapheresis. The drop was 13% of the IgG baseline value at 800mL collected plasma. Total protein, IgG and cell counts of the plasma product met current guidelines of plasma for fractionation. Donors' IgG levels during apheresis showed a steady decrease without compromising the quality of plasma product. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Analysis of Relationship between Serum Total Light Chain κ/λ Ratio and Proportion of Bone Marrow Plasma Cells in Patients with IgG type and IgA type Multiple Myeloma].

PubMed

Zhu, An-You; Zhu, Fang-Bing; Wang, Feng-Chao; Zhang, Lun-Jun; Ma, Yue; Hu, Jian-Guo

2017-10-01

To explore the relationship between serum total light chain κ/λ ratio (sTLC-κ/λ) and proportion of bone marrow plasma cells (BMPC) in patients with IgG type and IgA type multiple myeloma (MM) and its clinical significance. The levels of serum IgG, IgA, κ type and λ type total light chain were detected in 79 newly diagnosed patients with IgG type (n=52) and IgA type (n=27) MM by immuno-nephelometric assay and the sTLC-κ/λ ratio was calculated. The proportion of BMPC was determined by bone marrow smears in the corresponding period, and the changes in sTLC-κ/λ ratio and the proportion of BMPC were observed in 19 patients with IgG type(n=16) and IgA type (n=3) MM undergoing treatment, 26 cases of non-phasmocytic proliferative diseases were enrolled in control group. In MM patients with IgGκ type and IgAκ type, the sTLC-κ/λ ratio was significantly higher than that in the control group (P<0.01), while in MM patients with IgGλ type and IgAλ type, the sTLC-κ/λ ratio was significantly lower than that in the control group (P<0.01). In MM patients with IgGκ, the sTLC-κ/λ ratio was significantly higher than that in MM patients with IgAκ(P<0.01), while the sTLC-κ/λ ratio in MM patients with IgGλ was significantly lower than that in MM patients with IgAλ. The sTLC-κ/λ ratios in MM patients with IgGκ and IgAκ were positively correlated with the concentrations of IgG (r=0.778,P=0.000) and IgA (r=0.601,P=0.039), while the sTLC-κ/λ ratios of patients with IgGλ and IgAλ were negativily correlated with the IgG(r=-0.586,P=0.01) and IgA level(r=-0.718,P=0.003). In addition, a correlation between each type MM was not found except the IgGκ type MM which had a positive correlation between the sTLC-κ/λ ratio and proportion of BMPC (r=0.579,P=0.002). Nonetheless, 18 of 19 patients with IgG type and IgA type MM undergoing treatment showed concordance between the sTLC-κ/λ ratio and proportion of BMPC change. There is a lower correlation between the sTLC-κ/λ ratio and the proportion of BMPC in MM patients with IgG type and IgA type, but there is a high concordance between the sTLC-κ/λ ratio and the proportion of BMPC change in the same patient and it suggests that the sTLC-κ/λ ratio plays an important role in the diagnosis and monitoring of IgG type and IgA type MM.

B cell subsets and dysfunction of regulatory B cells in IgG4-related diseases and primary Sjögren's syndrome: the similarities and differences.

PubMed

Lin, Wei; Jin, Lixia; Chen, Hua; Wu, Qingjun; Fei, Yunyun; Zheng, Wenjie; Wang, Qian; Li, Ping; Li, Yongzhe; Zhang, Wen; Zhao, Yan; Zeng, Xiaofeng; Zhang, Fengchun

2014-05-29

IgG4-related disease (IgG4-RD) is a multisystem-involved autoimmune disease. Abnormally activated and differentiated B cells may play important roles. Regulatory B cells (Breg) are newly defined B cell subgroups with immunosuppressive functions. In this study, we investigated the differences of B cell subsets, the expressions of co-stimulatory molecules on B cells, and the function of Breg cells in patients with IgG4-RD, primary Sjögren's syndrome (pSS) as well as in healthy controls (HC). Newly diagnosed IgG4-RD patients (n = 48) were enrolled, 38 untreated pSS patients and 30 healthy volunteers were recruited as disease and healthy controls. To analyze B cell subsets and B cell activity, PBMCs were surface stained and detected by flow cytometry. The function of Breg cells was tested by coculturing isolated CD19 + CD24(hi)CD38(hi) Breg cells with purified CD4 + CD25- T cells. Serum cytokines were measured by ELISA and cytometric bead array. Relationship between clinical data and laboratory findings were analyzed as well. Compared with pSS patients and HC, IgG4-RD patients had a lower frequency of peripheral Breg cells. Interestingly, CD19 + CD24-CD38(hi) B cell subsets were significantly higher in peripheral B cells from IgG4-RD patients than in pSS patients and HC, which correlated with serum IgG4 levels. The expression of BAFF-R and CD40 on B cells was significantly lower in IgG4-RD patients compared with those in pSS patients and HC. Unlike HC, Breg cells from pSS patients lacked suppressive functions. B cells in patients with IgG4-RD and pSS display a variety of abnormalities, including disturbed B cell subpopulations, abnormal expression of key signaling molecules, co-stimulatory molecules, and inflammatory cytokines. In addition, a significantly increased B cell subset, CD19 + CD24-CD38(hi) B cells, may play an important role in the pathogenesis of IgG4-RD.

Free kappa light chains in cerebrospinal fluid as a biomarker to assess risk conversion to multiple sclerosis.

PubMed

Menéndez-Valladares, P; García-Sánchez, M I; Cuadri Benítez, P; Lucas, M; Adorna Martínez, M; Carranco Galán, V; García De Veas Silva, J L; Bermudo Guitarte, C; Izquierdo Ayuso, G

2015-01-01

Multiple sclerosis (MS) initiates with a first attack or clinically isolated syndrome (CIS). The importance of an early treatment in MS leads to the search, as soon as possible, for novel biomarkers which can predict conversion from CIS to MS. The purpose of this study was to assess the predictive value of the kappa index ([Formula: see text] index), using kappa free light light chains ([Formula: see text]FLCs) in cerebrospinal fluid (CSF), for the conversion of CIS patients to MS, and compare its accuracy with other parameters used in clinical practice. FLC levels were analysed in CSF from 176 patients: 70 as control group, 77 CIS, and 29 relapsing-remitting MS. FLC levels were quantified by nephelometry. [Formula: see text] Index sensitivity and specificity (93.1%; 95.7%) was higher than those from the immunoglobulin G (IgG) index (75.9%; 94.3%), and lower than those from oligoclonal IgG bands (OCGBs) (96.5%; 98.6%). The optimal cut-off for [Formula: see text] index was 10.62. Most of the CIS patients with [Formula: see text] index >10.62 presented OCGBs, IgG index >0.56 and fulfilled magnetic resonance imaging (MRI) criteria. CIS patients above [Formula: see text] index cut-off of 10.62 present 7.34-fold risk of conversion to MS than CIS below this value. The [Formula: see text] index correlated with positive OCGBs, IgG index above 0.56 and MRI criteria.

Free kappa light chains in cerebrospinal fluid as a biomarker to assess risk conversion to multiple sclerosis

PubMed Central

Menéndez-Valladares, P; García-Sánchez, MI; Cuadri Benítez, P; Lucas, M; Adorna Martínez, M; Carranco Galán, V; García De Veas Silva, JL; Bermudo Guitarte, C

2015-01-01

Background Multiple sclerosis (MS) initiates with a first attack or clinically isolated syndrome (CIS). The importance of an early treatment in MS leads to the search, as soon as possible, for novel biomarkers which can predict conversion from CIS to MS. Objective The purpose of this study was to assess the predictive value of the kappa index (κ index), using kappa free light light chains (κFLCs) in cerebrospinal fluid (CSF), for the conversion of CIS patients to MS, and compare its accuracy with other parameters used in clinical practice. Methods FLC levels were analysed in CSF from 176 patients: 70 as control group, 77 CIS, and 29 relapsing–remitting MS. FLC levels were quantified by nephelometry. Results κ Index sensitivity and specificity (93.1%; 95.7%) was higher than those from the immunoglobulin G (IgG) index (75.9%; 94.3%), and lower than those from oligoclonal IgG bands (OCGBs) (96.5%; 98.6%). The optimal cut-off for κ index was 10.62. Most of the CIS patients with κ index >10.62 presented OCGBs, IgG index >0.56 and fulfilled magnetic resonance imaging (MRI) criteria. Conclusion CIS patients above κ index cut-off of 10.62 present 7.34-fold risk of conversion to MS than CIS below this value. The κ index correlated with positive OCGBs, IgG index above 0.56 and MRI criteria. PMID:28607709

Co-expression of Interleukin-15 Enhances the Protective Immune Responses Induced by Immunization with a Murine Malaria MVA-Based Vaccine Encoding the Circumsporozoite Protein.

PubMed

Parra, Marcela; Liu, Xia; Derrick, Steven C; Yang, Amy; Molina-Cruz, Alvaro; Barillas-Mury, Carolina; Zheng, Hong; Thao Pham, Phuong; Sedegah, Martha; Belmonte, Arnel; Litilit, Dianne D; Waldmann, Thomas A; Kumar, Sanjai; Morris, Sheldon L; Perera, Liyanage P

2015-01-01

Malaria remains a major global public health problem with an estimated 200 million cases detected in 2012. Although the most advanced candidate malaria vaccine (RTS,S) has shown promise in clinical trials, its modest efficacy and durability have created uncertainty about the impact of RTS,S immunization (when used alone) on global malaria transmission. Here we describe the development and characterization of a novel modified vaccinia virus Ankara (MVA)-based malaria vaccine which co-expresses the Plasmodium yoelii circumsporozoite protein (CSP) and IL-15. Vaccination/challenge studies showed that C57BL/6 mice immunized with the MVA-CSP/IL15 vaccine were protected significantly better against a P. yoelii 17XNL sporozoite challenge than either mice immunized with an MVA vaccine expressing only CSP or naïve controls. Importantly, the levels of total anti-CSP IgG were elevated about 100-fold for the MVA-CSP/IL15 immunized group compared to mice immunized with the MVA-CSP construct that does not express IL-15. Among the IgG subtypes, the IL-15 expressing MVA-CSP vaccine induced levels of IgG1 (8 fold) and IgG2b (80 fold) higher than the MVA-CSP construct. The significantly enhanced humoral responses and protection detected after immunization with the MVA-CSP/IL15 vaccine suggest that this IL-15 expressing MVA construct could be considered in the development of future malaria immunization strategies.

Assessment of IgG Antibodies Against HSV1, HSV2, CMV and EBV in Patients with Pemphigus Vulgaris Versus Healthy People

PubMed Central

Ghalayani, Parichehr; Rashidi, Fateme; Saberi, Zahra

2015-01-01

Objectives: Regarding the implication of viruses particularly herpes in pemphigus vulgaris, we sought to assess and compare the level of immunoglobulin G (IgG) antibodies against herpes simplex virus types 1 and 2 (HSV1 and HSV2), cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in patients with pemphigus vulgaris and healthy people. Materials and Methods: In this cross-sectional study, 25 patients with pemphigus vulgaris and 27 healthy individuals comprised the experimental and control groups, respectively. Serum samples were taken from both groups; the levels of IgG antibodies against HSV1, HSV2, CMV and EBV were measured using ELISA. Results: Immunoglobulin G titer was higher for all four viruses in the patient group in comparison to the control group. This difference was significant for anti-EBV (P= 0.005), anti-CMV (P=0.0001) and anti-HSV2 (P=0.001) but not significant for anti-HSV1 (P= 0.36). Conclusion: Viruses including EBV, CMV, and HSV2 probably play a role in the pathogenesis of pemphigus in addition to the effects of genetics, toxins and other predisposing factors. In this study, no statistically significant relationship was observed between HSV1 and pemphigus vulgaris, which was probably due to the high titer of anti-HSV1 IgG in healthy individuals in the community. More studies must be done in this regard. PMID:27507994

Heritability analysis of IgG4 antibodies in autoimmune thyroid disease.

PubMed

Outschoorn, I M; Talor, M V; Burek, C L; Hoffman, W H; Rose, N R

2014-08-01

A study of IgG4 autoantibody levels in juvenile thyroid disease patients showed evidence of heritability using the ROMP screening method. These levels increased with time despite the fact that total IgG antibody decreased with time. Evidence of heritability was demonstrated only in patients with high titers of autoantibodies to both thyroglobulin (Tg) and thyroperoxidase (TPO) unlike family members who may show high titers of one or the other and be asymptomatic at the time of sampling. Since high and low IgG4 levels give different heritability plots, these findings may represent a more severe fibrotic form of thyroiditis with a distinct genetic background. Hence a simple predictive approach is offered by this screening tool for the disease in patients and family members which may be helpful in the future to identify IgG4-related thyroiditis early in the course of disease without the requirement for biopsy.

Allergen-specific IgG and IgA in serum and bronchoalveolar lavage fluid in a model of experimental feline asthma.

PubMed

Norris, C R; Byerly, J R; Decile, K C; Berghaus, R D; Walby, W F; Schelegle, E S; Hyde, D M; Gershwin, L J

2003-12-15

Allergic asthma, a Th2 cell driven response to inhaled allergens, has classically been thought of as predominantly mediated by IgE antibodies. To investigate the role of other immunoglobulin classes (e.g., IgG and IgA) in the immunopathogenesis of allergic asthma, levels of these allergen-specific immunoglobulins were measured in serum and mucosal fluids. Bermuda grass allergen (BGA)-specific IgG and IgA ELISAs in serum and bronchoalveolar lavage fluid (BALF) were developed and optimized in an experimental model of BGA-induced feline asthma. Levels of BGA-specific IgG and IgA significantly increased over time in serum and BALF after allergen sensitization. Additionally, these elevated levels of BGA-specific IgG and IgA were seen in conjunction with the development of an asthmatic phenotype indicated by positive intradermal skin tests, enhanced airways hyperreactivity, and increased eosinophil percentages in the BALF.

The influence of intestinal parasites on Plasmodium vivax-specific antibody responses to MSP-119 and AMA-1 in rural populations of the Brazilian Amazon.

PubMed

Sánchez-Arcila, Juan Camilo; de França, Marcelle Marcolino; Pereira, Virginia Araujo; Vasconcelos, Mariana Pinheiro Alves; Têva, Antonio; Perce-da-Silva, Daiana de Souza; Neto, Joffre Rezende; Aprígio, Cesarino Junior Lima; Lima-Junior, Josue da Costa; Rodrigues, Mauricio Martins; Soares, Irene Silva; Banic, Dalma Maria; Oliveira-Ferreira, Joseli

2015-11-06

Polyparasitism is a common condition in humans but its impact on the host immune system and clinical diseases is still poorly understood. There are few studies of the prevalence and the effect of malaria-intestinal parasite co-infections in the immune response to malaria vaccine candidates. The present study determines whether the presence of malaria and intestinal parasites co-infection is associated with impaired IgG responses to Plasmodium vivax AMA-1 and MSP-119 in a rural population of the Brazilian Amazon. A cross-sectional survey was performed in a rural area of Rondonia State and 279 individuals were included in the present study. At recruitment, whole blood was collected and Plasmodium and intestinal parasites were detected by microscopy and molecular tests. Blood cell count and haemoglobin were also tested and antibody response specific to P. vivax AMA-1 and MSP-119 was measured in plasma by ELISA. The participants were grouped according to their infection status: singly infected with Plasmodium (M); co-infected with Plasmodium and intestinal parasites (CI); singly infected with intestinal parasites (IP) and negative (N) for both malaria and intestinal parasites. The prevalence of intestinal parasites was significantly higher in individuals with malaria and protozoan infections were more prevalent. IgG antibodies to PvAMA-1 and/or PvMSP-119 were detected in 74 % of the population. The prevalence of specific IgG was similar for both proteins in all four groups and among the groups the lowest prevalence was in IP group. The cytophilic sub-classes IgG1 and IgG3 were predominant in all groups for PvAMA-1 and IgG1, IgG3 and IgG4 for PvMSP-119. In the case of non-cytophilic antibodies to PvAMA-1, IgG2 was significantly higher in IP and N group when compared to M and CI while IgG4 was higher in IP group. The presence of intestinal parasites, mainly protozoans, in malaria co-infected individuals does not seem to alter the antibody immune responses to P. vivax AMA-1 and MSP-119. However, IgG response to both AMA1 and MSP1 were lower in individuals with intestinal parasites.

Absence of antibodies against Bordetella pertussis in pregnant women and newborns in the state of Nuevo Leon.

PubMed

Villarreal-Pérez, Jesús Zacarías; Ramírez-Aranda, José Manuel; Rodríguez-Rodríguez, Irasema; Perales-Dávila, José; García-Elizondo, Francisco Javier; Gómez-Gómez, Celina; Galindo-Galindo, Edgar; Rodríguez-Moreno, Marco Antonio; Ballesteros-Elizondo, Romelia

2014-09-01

To assess placental transfer of antibodies to the child at birth and at 2 months of age. For the quantification of anti-PT IgG antibodies, we used an indirect enzyme-linked immunosorbent assay standardized by The National Institute of Epidemiologic Diagnosis and Reference (InDRE). Samples were considered negative from 0 to 48 IU/mL, indeterminate from 49 to 93 IU/mL and positive at ≥94 IU/mL. We performed a cross-sectional assessment of anti-PT IgG antibody levels in the mother, umbilical cord, and child. There was a higher concentration of IgG anti-TP in the umbilical cord (4.3%) and in the mother (1.4%), but a total absence was observed in the child (0%). The vulnerability of children to Bordetella pertussis shows the need to implement effective immunization strategies, whether actively, in the child, or passively through the mother, adolescents, and adults who are in contact with the child.

[The diagnostic value of anti-CMV and anti-HPV-B19 antiviral antibodies in studies on causes of recurrent abortions].

PubMed

Szkaradkiewicz, A; Pieta, P; Tułecka, T; Breborowicz, G; Słomko, Z; Strzyzowski, P

1997-04-01

Presence of serum anti-cytomegalovirus (CMV) and anti-parvovirus B19 (HPV-B19) antibodies was studied in 11 women within the first day after consecutive spontaneous abortion in the second trimester of pregnancy and in the control group, consisting of 15 women in the second trimester of a normal pregnancy. Most of studied women manifested presence of serum IgG class anti-CMV antibodies (IgG-anti-CMV) and levels of the antibodies proved significantly higher in women following spontaneous abortions. The patients frequently demonstrated in parallel presence of serum IgG class anti-HPV-B19 antibodies. In one patient a generalised nonimmunological hydrops fetalis was disclosed and her serum contained IgM and IgG class antibodies against CMV as well as against HPV-B19. The results suggest that in majority of the studied women the spontaneous abortion might have resulted from fetal infection due to reactivation of chronic CMV infection in the course of pregnancy.

Levels of diphtheria and tetanus specific IgG of Portuguese adult women, before and after vaccination with adult type Td. Duration of immunity following vaccination

PubMed Central

Gonçalves, Guilherme; Santos, Maria Augusta; Frade, João Graça; Cunha, José Saraiva

2007-01-01

Background The need for tetanus toxoid decennial booster doses has been questioned by some experts. Several counter arguments have been presented, supporting the maintenance of decennial adult booster doses with tetanus and diphtheria toxoids (adult formulation of the vaccine: Td). This study aimed to evaluate the use of Td in Portuguese adult women under routine conditions. For that purpose we selected a group of women 30+ years of age to which vaccination was recommended. We intended to know if pre-vaccination antibody concentrations were associated with factors as age at first and last vaccination, number of doses and time since last revaccination. We also intended to assess the serological efficacy of Td booster. Methods Following the Portuguese guidelines 100 women were vaccinated with Td. Antitetanus toxin IgG (ATT IgG) and antidiphtheria toxin IgG (ADT IgG) levels were measured (mIU/ml) in 100 pre-vaccination and 91 post-vaccination sera. Detailed vaccination records were available from 88 participants. Results Twenty-two women (Group A) began vaccination with DPT/DT in their early childhood and their pre-vaccination ATT IgG levels increased with the number of doses received (p = 0.022) and decreased with time since last vaccination (p = 0.016). Among the 66 women who began vaccination in adolescence and adulthood (Group B), with monovalent TT, ATT IgG levels decreased with age at first dose (p < 0.001) and with time since last vaccination (p = 0.041). In Group A, antidiphtheria toxin IgG kinetics was very similar to that observed for ATT IgG. Among women not vaccinated with diphtheria toxoid, ADT IgG levels decreased with age. Serological response to both components of Td was good but more pronounced for ATT IgG. Conclusion Our study suggests that, to protect against tetanus, there is no need to administer decennial boosters to the Portuguese adults who have complied with the childhood/adolescent schedule (6 doses of tetanus toxoid). The adult booster intervals could be wider, probably of 20 years. This also seems to apply to protection against diphtheria, but issues on the herd immunity and on the circulation of toxigenic strains need to be better understood. PMID:17565697

Stabilization of IgG1 in spray-dried powders for inhalation.

PubMed

Schüle, S; Schulz-Fademrecht, T; Garidel, P; Bechtold-Peters, K; Frieb, W

2008-08-01

The protein stabilizing capabilities of spray-dried IgG1/mannitol formulations were evaluated. The storage stability was tested at different residual moisture levels prepared by vacuum-drying or equilibration prior to storage. Vacuum-drying at 32 degrees C/0.1mbar for 24h reduced the moisture level below 1%, constituting an optimal basis for improved storage stability. The crystalline IgG1/mannitol powders with a weight ratio of 20/80 up to 40/60 failed to prevent the antibody aggregation as assessed by size exclusion chromatography during storage. Ratios of 60/40 up to 80/20 IgG1/mannitol provided superior stability of the antibody and the powders could be produced with high yields. The lower the residual moisture, the better was the stabilizing capability. An amount of 20% mannitol provided the best stabilization. Storage stability of 60/40, 70/30, and 80/20 IgG1/mannitol formulations over one year was adequate at 2-8 degrees C and 25 degrees C. Closed storage (sealed in vials) at 40 degrees C/75% RH and open storage at 25 degrees C/60% RH revealed that the stability still required optimization. The lower the protein content, the better was the powder flowability. The aerodynamic properties of powders spray-dried with 10% solids content were inadequate, as the particle size ranged between 5.1 and 7.2 microm and the fine particle fraction accounted for only 4-11%. Reduction of the solids content to 2.5% did improve the aerodynamic properties as the mass mean aerodynamic diameter was reduced to 3.6 microm and the fine particle fraction was increased to about 14%. The reduction of the solids content did not influence the storage stability significantly. Also spray-drying at higher temperatures had no significant impact on the storage stability, despite a higher tendency to form amorphous systems. In order to improve the storage stability and to maintain the good flowability of 70/30 IgG1/mannitol powder or to keep the storage stability but to improve the flowability of the 80/20 IgG1/mannitol powder, mannitol was partially substituted by a second excipient such as trehalose, sucrose, glycine, lactose, lactosucrose, or dextran 1. Differences in the stabilizing capability were noticeable upon closed storage at 40 degrees C/75% RH and open powder storage. Protein stabilization was improved by the addition of glycine but trehalose and sucrose were most effective in preventing aggregation, which can be primarily attributed to the water replacement properties of the sugars. The addition of another excipient, isoleucine had positive effects on both flowability and protein stability.

An aortoduodenal fistula as a complication of immunoglobulin G4-related disease

PubMed Central

Sarac, Momir; Marjanovic, Ivan; Bezmarevic, Mihailo; Zoranovic, Uros; Petrovic, Stanko; Mihajlovic, Miodrag

2012-01-01

Most primary aortoduodenal fistulas occur in the presence of an aortic aneurysm, which can be part of immunoglobulin G4 (IgG4)-related sclerosing disease. We present a case who underwent endovascular grafting of an aortoduodenal fistula associated with a high serum IgG4 level. A 56-year-old male underwent urgent endovascular reconstruction of an aortoduodenal fistula. The patient received antibiotics and other supportive therapy, and the postoperative course was uneventful, however, elevated levels of serum IgG, IgG4 and C-reactive protein were noted, which normalized after the introduction of steroid therapy. Control computed tomography angiography showed no endoleaks. The primary aortoduodenal fistula may have been associated with IgG4-related sclerosing disease as a possible complication of IgG4-related inflammatory aortic aneurysm. Endovascular grafting of a primary aortoduodenal fistula is an effective and minimally invasive alternative to standard surgical repair. PMID:23155348

IgG4-Associated Cholangitis Can Mimic Hilar Cholangiocarcinoma.

PubMed

Zaydfudim, Victor M; Wang, Andrew Y; de Lange, Eduard E; Zhao, Zimin; Moskaluk, Christopher A; Bauer, Todd W; Adams, Reid B

2015-07-01

IgG4-associated cholangitis can mimic hilar cholangiocarcinoma. Previously reported patients with IgG4-associated cholangitis mimicking cholangiocarcinoma had elevated serum IgG4 levels and long-segment biliary strictures. However, in the absence of other diagnostic criteria for malignancy, IgG4-associated cholangitis should remain a consideration among patients with normal serum IgG4 and a hilar mass suspicious for cholangiocarcinoma. The presence of a hilar mass and a malignant-appearing biliary stricture in two patients with normal serum IgG4 prompted further evaluation and subsequent concomitant liver and bile duct resection and reconstruction. The diagnosis of IgG4-associated cholangitis was established during the pathologic evaluation of the resected specimens. IgG4-associated cholangitis is a known imitator of hilar cholangiocarcinoma and should be considered in the differential diagnosis even among serologically IgG4-negative patients with a hilar mass prior to operative resection.

Protection against Fasciola gigantica using paramyosin antigen as a candidate for vaccine production.

PubMed

Abou-Elhakam, H; Rabee, I; El Deeb, S; El Amir, A

2013-11-15

Yet no vaccine to protect ruminants against liver fluke infection has been commercialized. In an attempt to develop a suitable vaccine against Fasciola gigantica (F. gigantica) infection in rabbits, using 97 kDa Pmy antigen. It was found that, the mean worm burdens and bile egg count after challenge were reduced significantly by 58.40 and 61.40%, respectively. On the other hand, immunization of rabbits with Pmy induced a significant expression of humoral antibodies (IgM, total IgG, IgG1, IgG2 and IgG4) and different cytokines (IL-6, IL-10, L-12 and TNF-alpha). Among Ig isotypes, IgG2 and IgG4 were most dominant Post-infection (PI) while, recording a low IgG1 level. The dominance of IgG2 and IgG4 suggested late T helper1 (Th1) involvement in rabbit's cellular response. While, the low IgG1 level suggested Th2 response to adult F. gigantica worm Pmy. Among all cytokines, IL-10 was the highest in rabbits immunized with Pmy PI suggesting also the enhancement of Th2 response. It was clear that the native F. gigantica Pmy is considered as a relevant candidate for vaccination against fascioliasis. Also, these data suggested the immunoprophylactic effect of the native F. gigantica Pmy which is mediated by a mixed Th1/Th2 response.

Prime-boost vaccination with toxoplasma lysate antigen, but not with a mixture of recombinant protein antigens, leads to reduction of brain cyst formation in BALB/c mice.

PubMed

Wagner, Angelika; Schabussova, Irma; Ruttkowski, Bärbel; Peschke, Roman; Kur, Józef; Kundi, Michael; Joachim, Anja; Wiedermann, Ursula

2015-01-01

Infection with the ubiquitous parasite Toxoplasma gondii is a threat for immunocompromised patients and pregnant women and effective immune-prophylaxis is still lacking. Here we tested a mixture of recombinant T. gondii antigens expressed in different developmental stages, i.e., SAG1, MAG1 and GRA7 (SMG), and a lysate derived from T. gondii tachyzoites (TLA) for prophylactic vaccination against cyst formation. Both vaccine formulations were applied systemically followed by an oral TLA-booster in BALB/c mice. Systemic priming with SMG and oral TLA-booster did not show significant induction of protective immune responses. In contrast, systemic priming and oral booster with TLA induced higher levels of Toxoplasma-specific IgG, IgG1 and IgG2a in sera as well as high levels of Toxoplasma-specific IgG1 in small intestines. Furthermore, high levels of Toxoplasma-specific Th1-, Th17- and Th2-associated cytokines were only detected in restimulated splenocytes of TLA-vaccinated mice. Importantly, in mice orally infected with T. gondii oocysts, only TLA-vaccination and booster reduced brain cysts. Furthermore, sera from these mice reduced tachyzoites invasion of Vero cells in vitro, indicating that antibodies may play a critical role for protection against Toxoplasma infection. Additionally, supernatants from splenocyte cultures of TLA-vaccinated mice containing high levels of IFN-γ lead to substantial production of nitric oxide (NO) after incubation with macrophages in vitro. Since NO is involved in the control of parasite growth, the high levels of IFN-γ induced by vaccination with TLA may contribute to the protection against T. gondii. In conclusion, our data indicate that prime-boost approach with TLA, but not with the mixture of recombinant antigens SMG, induces effective humoral and cellular Toxoplasma-specific responses and leads to significant reduction of cerebral cysts, thereby presenting a viable strategy for further vaccine development against T. gondii infection.

Relationship between exposure to vector bites and antibody responses to mosquito salivary gland extracts.

PubMed

Fontaine, Albin; Pascual, Aurélie; Orlandi-Pradines, Eve; Diouf, Ibrahima; Remoué, Franck; Pagès, Frédéric; Fusaï, Thierry; Rogier, Christophe; Almeras, Lionel

2011-01-01

Mosquito-borne diseases are major health problems worldwide. Serological responses to mosquito saliva proteins may be useful in estimating individual exposure to bites from mosquitoes transmitting these diseases. However, the relationships between the levels of these IgG responses and mosquito density as well as IgG response specificity at the genus and/or species level need to be clarified prior to develop new immunological markers to assess human/vector contact. To this end, a kinetic study of antibody levels against several mosquito salivary gland extracts from southeastern French individuals living in three areas with distinct ecological environments and, by implication, distinct Aedes caspius mosquito densities were compared using ELISA. A positive association was observed between the average levels of IgG responses against Ae. caspius salivary gland extracts and spatial Ae. caspius densities. Additionally, the average level of IgG responses increased significantly during the peak exposure to Ae. caspius at each site and returned to baseline four months later, suggesting short-lived IgG responses. The species-specificity of IgG antibody responses was determined by testing antibody responses to salivary gland extracts from Cx. pipiens, a mosquito that is present at these three sites at different density levels, and from two other Aedes species not present in the study area (Ae. aegypti and Ae. albopictus). The IgG responses observed against these mosquito salivary gland extracts contrasted with those observed against Ae. caspius salivary gland extracts, supporting the existence of species-specific serological responses. By considering different populations and densities of mosquitoes linked to environmental factors, this study shows, for the first time, that specific IgG antibody responses against Ae. caspius salivary gland extracts may be related to the seasonal and geographical variations in Ae. caspius density. Characterisation of such immunological-markers may allow the evaluation of the effectiveness of vector-control strategies or estimation of the risk of vector-borne disease transmission.

Relationship between Exposure to Vector Bites and Antibody Responses to Mosquito Salivary Gland Extracts

PubMed Central

Orlandi-Pradines, Eve; Diouf, Ibrahima; Remoué, Franck; Pagès, Frédéric; Fusaï, Thierry; Rogier, Christophe; Almeras, Lionel

2011-01-01

Mosquito-borne diseases are major health problems worldwide. Serological responses to mosquito saliva proteins may be useful in estimating individual exposure to bites from mosquitoes transmitting these diseases. However, the relationships between the levels of these IgG responses and mosquito density as well as IgG response specificity at the genus and/or species level need to be clarified prior to develop new immunological markers to assess human/vector contact. To this end, a kinetic study of antibody levels against several mosquito salivary gland extracts from southeastern French individuals living in three areas with distinct ecological environments and, by implication, distinct Aedes caspius mosquito densities were compared using ELISA. A positive association was observed between the average levels of IgG responses against Ae. caspius salivary gland extracts and spatial Ae. caspius densities. Additionally, the average level of IgG responses increased significantly during the peak exposure to Ae. caspius at each site and returned to baseline four months later, suggesting short-lived IgG responses. The species-specificity of IgG antibody responses was determined by testing antibody responses to salivary gland extracts from Cx. pipiens, a mosquito that is present at these three sites at different density levels, and from two other Aedes species not present in the study area (Ae. aegypti and Ae. albopictus). The IgG responses observed against these mosquito salivary gland extracts contrasted with those observed against Ae. caspius salivary gland extracts, supporting the existence of species-specific serological responses. By considering different populations and densities of mosquitoes linked to environmental factors, this study shows, for the first time, that specific IgG antibody responses against Ae. caspius salivary gland extracts may be related to the seasonal and geographical variations in Ae. caspius density. Characterisation of such immunological-markers may allow the evaluation of the effectiveness of vector-control strategies or estimation of the risk of vector-borne disease transmission. PMID:22195000

Re-examination of immune response and estimation of anti-Vi IgG protective threshold against typhoid fever-based on the efficacy trial of Vi conjugate in young children

PubMed Central

Szu, Shousun C.; Klugman, Keith P.; Hunt, Steven

2014-01-01

Background The capsular polysaccharide of Salmonella enterica serovar Typhi, Vi antigen, is an essential virulence factor and a protective antigen. Similar to other polysaccharide vaccines, the protective action of Vi, both to the polysaccharide alone or when presented as a conjugate, is mediated by serum IgG Vi antibodies. The evaluation of Vi capsular polysaccharide based vaccines to prevent typhoid fever would be significantly facilitated by the identification of a “protective level” of serum antibodies to Vi antigen. Methods The protective level of anti-Vi IgG against typhoid fever was derived from the protective efficacy and immune response of a Vi-rEPA conjugate vaccine efficacy trial. The estimation was derived by two methods: correlation of the percent efficacy and the antibody distribution profile in the vaccine group at a given period of observation, and use of the relative ratio of anti-Vi IgG levels between the vaccine and placebo groups greater or equal to the Relative Risk of typhoid fever used in the efficacy determination. Results Both methods predicted a similar range of a minimum protective level of anti-Vi IgG between 1.4 and 2.0 μg/ml (short term threshold). When applying a protective threshold of 10 μg/ml at 6 months post immunization, an IgG level in excess of 1.4 μg/ml was achieved by 90% of children at 46 months post immunization, consistent with an 89% level of protection over the duration of the study. We thus suggest that the proportion of children with Vi IgG > 10 μg/ml (long term threshold) 6 months after immunization may reflect the proportion protected over at least a 4 year period. Conclusion The current assignment of an anti-Vi IgG protective level may be of value when evaluating vaccine performance of future Vi conjugate vaccines. PMID:24630869

Performance of two Aspergillus IgG EIA assays compared with the precipitin test in chronic and allergic aspergillosis.

PubMed

Baxter, C G; Denning, D W; Jones, A M; Todd, A; Moore, C B; Richardson, M D

2013-04-01

Detection of Aspergillus IgG antibodies is important in the diagnosis of chronic pulmonary aspergillosis and allergic bronchopulmonary aspergillosis. Immunoprecipitation techniques to detect these antibodies appear to lack sensitivity and accurate quantitation compared with enzyme immunoassays (EIA). This study assessed the performance of two commercial EIAs compared with counterimmunoelectrophoresis (CIE). This was a prospective cohort study of 175 adult patients with chronic or allergic pulmonary aspergillosis. Aspergillus IgG antibodies were detected using CIE, Phadia ImmunoCap Aspergillus IgG and Bio-Rad Platelia Aspergillus IgG. Inter-assay reproducibility was determined for each method and 25 patients had two serum samples analysed within a 6-month interval. When compared with CIE, both ImmunoCap and Platelia Aspergillus IgG had good sensitivity (97 and 93%, respectively) for detection of Aspergillus IgG antibodies. The level of agreement between the two EIAs for positive results was good, but the concentration of antibodies was not correlated between the tests or with CIE titre. ImmunoCap IgG inter-assay coefficient of variation was 5%, whereas Platelia IgG was 33%. Median ImmunoCap IgG values for CPA and allergic aspergillosis were 95 and 32 mg/L, respectively, whereas Platelia IgG values were >80 and 6 AU/mL. The direction of CIE titre change over 6 months was mirrored by ImmunoCap IgG levels in 92% of patients, and by Platelia IgG in 72% of patients. Both ImmunoCap and Platelia Aspergillus IgG EIAs are sensitive measures of Aspergillus IgG antibodies compared with CIE. However, ImmunoCap appears to have better reproducibility and may be more suitable for monitoring patient disease. © 2012 The Authors Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases.

Adjuvant-enhanced antibody and cellular responses to inclusion bodies expressing FhSAP2 correlates with protection of mice to Fasciola hepatica.

PubMed

Rivera, Francheska; Espino, Ana M

2016-01-01

Fasciola hepatica saposin-like protein-2 (FhSAP2) is a protein differentially expressed in various developmental stages of F. hepatica. Recombinant FhSAP2 has demonstrated the induction of partial protection in mice and rabbits when it is administered subcutaneously (SC) in Freund's adjuvant. Because FhSAP2 is overexpressed in bacteria in the form of inclusion bodies (IBs), we isolated IBs expressing FhSAP2 and tested their immunogenicity when administered SC in mice emulsified in two different adjuvants: QS-21 and Montanide TM ISA720. Animals received three injections containing 20 μg of protein two weeks apart and 4 weeks after the third injection, mice were infected with 10 F. hepatica metacercariae by oral route. The percentages of protection induced by FhSAP2-IBs were estimated to be between 60.0 and 62.5% when compared with adjuvant-vaccinated, infected controls. By determining the levels of IgG1 and IgG2a antibodies and IL-4 and IFNγ cytokines in the serum of experimental animals, it was found that both Th1 and Th2 immune responses were significantly increased in the FhSAP2-IBs vaccinated groups compared with the adjuvant-vaccinated, infected control groups. The adjuvant-vaccinated groups had significantly lower IgG1 to IgG2a ratios and lower IL-4 to IFNγ ratios than the FhSAP2-IBs vaccinated animals, which is indicative of higher levels of Th2 immune responses. Irrespective to the adjuvant used, animals vaccinated with FhSAP2-IBs exhibited significantly higher survival percentage and less liver damage than the adjuvant-control groups. This study suggests that FhSAP2 has potential as vaccine against F. hepatica and that the protection elicited by this molecule could be linked to a mechanism driven by the CD4-Th1 cells. Published by Elsevier Inc.

Australian Aboriginal Children with Otitis Media Have Reduced Antibody Titers to Specific Nontypeable Haemophilus influenzae Vaccine Antigens

PubMed Central

Kirkham, Lea-Ann S.; Corscadden, Karli J.; Wiertsema, Selma P.; Fuery, Angela; Jones, B. Jan; Coates, Harvey L.; Vijayasekaran, Shyan; Zhang, Guicheng; Keil, Anthony; Richmond, Peter C.

2017-01-01

ABSTRACT Indigenous populations experience high rates of otitis media (OM), with increased chronicity and severity, compared to those experienced by their nonindigenous counterparts. Data on immune responses to otopathogenic bacteria in these high-risk populations are lacking. Nontypeable Haemophilus influenzae (NTHi) is the predominant otopathogen in Australia. No vaccines are currently licensed to target NTHi; however, protein D (PD) from NTHi is included as a carrier protein in the 10-valent pneumococcal polysaccharide conjugate vaccine (PHiD10-CV), and other promising protein vaccine candidates exist, including outer membrane protein 4 (P4) and protein 6 (P6). We measured the levels of serum and salivary IgA and IgG against PD, P4, and P6 in Aboriginal and non-Aboriginal children with chronic OM who were undergoing surgery and compared the levels with those in healthy non-Aboriginal children (controls). We found that Aboriginal cases had lower serum IgG titers to all NTHi proteins assessed, particularly PD. In contrast, serum IgA and salivary IgA and IgG titers to each of these 3 proteins were equivalent to or higher than those in both non-Aboriginal cases and healthy controls. While serum antibody levels increased with age in healthy controls, no changes in titers were observed with age in non-Aboriginal cases, and a trend toward decreasing titers with age was observed in Aboriginal cases. This suggests that decreased serum IgG responses to NTHi outer membrane proteins may contribute to the development of chronic and severe OM in Australian Aboriginal children and other indigenous populations. These data are important for understanding the potential benefits of PHiD10-CV implementation and the development of NTHi protein-based vaccines for indigenous populations. PMID:28151410

Antibodies attenuate the capacity of dendritic cells to stimulate HIV-specific cytotoxic T lymphocytes

PubMed Central

Posch, Wilfried; Cardinaud, Sylvain; Hamimi, Chiraz; Fletcher, Adam; Mühlbacher, Annelies; Loacker, Klaus; Eichberger, Paul; Dierich, Manfred P.; Pancino, Gianfranco; Lass-Flörl, Cornelia; Moris, Arnaud; Saez-Cirion, Asier; Wilflingseder, Doris

2014-01-01

Background Control of HIV is suggested to depend on potent effector functions of the virus-specific CD8+ T-cell response. Antigen opsonization can modulate the capture of antigen, its presentation, and the priming of specific CD8+ T-cell responses. Objective We have previously shown that opsonization of retroviruses acts as an endogenous adjuvant for dendritic cell (DC)–mediated induction of specific cytotoxic T lymphocytes (CTLs). However, in some HIV-positive subjects, high levels of antibodies and low levels of complement fragments coat the HIV surface. Methods Therefore we analyzed the effect of IgG opsonization on the antigen-presenting capacity of DCs by using CD8+ T-cell proliferation assays after repeated prime boosting, by measuring the antiviral activity against HIV-infected autologous CD4+ T cells, and by determining IFN-γ secretion from HIV-specific CTL clones. Results We find that DCs exposed to IgG-opsonized HIV significantly decreased the HIV-specific CD8+ T-cell response compared with the earlier described efficient CD8+ T-cell activation induced by DCs loaded with complement-opsonized HIV. DCs exposed to HIV bearing high surface IgG levels after incubation in plasma from HIV-infected subjects acted as weak stimulators for HIV-specific CTL clones. In contrast, HIV opsonized with plasma from patients exhibiting high complement and low IgG deposition on the viral surface favored significantly higher activation of HIV-specific CD8+ T-cell clones. Conclusion Our ex vivo and in vitro observations provide the first evidence that IgG opsonization of HIV is associated with a decreased CTL-stimulatory capacity of DCs. PMID:23063584

Differences in IgG responses against infection phase related Mycobacterium tuberculosis (Mtb) specific antigens in individuals exposed or not to Mtb correlate with control of TB infection and progression.

PubMed

Coppola, Mariateresa; Arroyo, Leonar; van Meijgaarden, Krista E; Franken, Kees Lmc; Geluk, Annemieke; Barrera, Luis F; Ottenhoff, Tom H M

2017-09-01

Tuberculosis (TB) occurs in only 3-10% of Mycobacterium tuberculosis (Mtb) infected individuals, suggesting that natural immunity can contain Mtb infection, although this remains poorly understood. Next to T-cells, a potentially protective role for B-cells and antibodies has emerged recently. However, the Mtb antigens involved remain ill-defined. Here, we investigated in a TB-endemic setting IgG levels against 15 Mtb antigens, representing various phases of Mtb infection and known to be potent human T-cell antigens. IgG levels against ESAT6/CFP10, Rv0440, Rv0867c, Rv1737c, Rv2029c, Rv2215, Rv2389c, Rv3616c and Mtb purified protein derivative (PPD) were higher in TB patients than in endemic and non-endemic controls. The only exception was Rv1733c that was preferentially recognized by antibodies from endemic controls compared to TB patients and non-endemic controls, suggesting a potential correlation with control of TB infection and progression. In patients, IgG levels against Ag85B and Rv2029c correlated with Mtb loads, while immunoglobulins against Rv0440 differed between genders. Our results support the potential role of certain Mtb antigen-(Rv1733c) specific antibodies in the control of TB infection and progression, while other Mtb antigen-specific antibodies correlate with TB disease activity and bacillary loads. The findings for Rv1733c agree with previous T-cell results and have implications for including antibody-mediated immunity in designing new strategies to control TB. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Immune complex orchitis in vasectomized rabbits

PubMed Central

1976-01-01

The results of the present study show that bilaterally vasectomized rabbits with high levels of antibodies to sperm antigens frequently develop an orchitis associated with granular deposits of rabbit IgG and C3 in the basement membranes of seminiferous tubules. The immune deposits correspond in location to electron-opaque deposits seen by electron microscopy. The "membranous orchitis" is characterized by thickening of tubular basement membranes, acc-mulation of macrophages and a few polymorphonuclear leukocytes, and destruction of the basal lamina, of the Sertoli and spermatogenetic cells. The pathogenetic role of the immune deposits and the possibility that they contain antigen- antibody complexes is indicated by: (a) selective accumulation of IgG and C3 granular deposits along the basement membranes of seminiferous tubules in rabbits producing high and persistent levels of antibodies to sperm antigens; (b) the elution of immunoglobulins from tissues with chaotropic ion-containing buffers, acid buffers, or heat; (c) the observation that the immuno-globulins accumulated in the testis contain antibody to sperm antigens; and (d) the demonstration of sperm antigens in a location similar to that of IgG and C3. It is postulated that sperm antigen-antibody complexes are formed in the basement membranes of seminiferous tubules when antigens leaking out of the tubules react with specific antibody coming from the circulation. In two rabbits with higher levels of circulating antisperm antibodies and severe orchitis, granular deposits of IgG and C3 were also present in renal glomeruli. Immunoglobulins eluted from the kidneys contained antibody with antisperm activity. These findings are consistent with the hypothesis that in some vasectomized rabbits extratesticular lesions may develop by a mechanism comparable to that of chronic serum sickness. PMID:129498

Immunogenicity and therapeutic effects of recombinant Ag85AB fusion protein vaccines in mice infected with Mycobacterium tuberculosis.

PubMed

Liang, Yan; Zhang, Junxian; Yang, Yourong; Bai, Xuejuan; Yu, Qi; Li, Ning; Hou, Ying; Shi, Yingchang; Wang, Lan; Wu, Xueqiong

2017-07-13

The immune function of tuberculosis (TB) patients is disordered. By using immune regulators to assist chemotherapy for TB the curative effect might be improved. In this study, a vaccine containing Mycobacterium tuberculosis (M. tuberculosis) recombinant Ag85AB fusion protein (rAg85AB) was constructed and evaluated. The mice were immunized intramuscularly three times at two-week intervals with Ag85AB fusion protein combined with Corynebacterium parvum adjuvant (rAg85AB+CP). In comparison to control mice that received either CP alone or saline, the mice that received rAg85AB+CP had significantly higher number of T cells secreting IFN-γ and higher levels of specific antibodies of IgG, IgG1 and IgG2a isotypes in sera. The specific antibodies also had higher ratios of IgG2a to IgG1, indicating a predominant Th1 immune response. To test for immunotherapy of TB, M. tuberculosis infected mice were given three intramuscular doses of 20μg, 40μg or 60μg of rAg85AB in rAg85AB+CP, or phosphate-buffered saline (PBS), or CP or Mycobacterium phlei (M. Phlei) F.U.36. Compared with the PBS group, 20µg, 40µg and 60µg rAg85AB+CP and M. phlei F.U.36 groups reduced the pulmonary bacterial loads by 0.13, 0.15, 0.42 and 0.40 log 10 , and the liver bacterial loads by 0.64, 0.64, 0.53 and 0.61 log 10 , respectively. Pathological changes of lungs were less, and the lesions were limited to a certain extent in 40µg and 60µg rAg85AB+CP and M. phlei F.U.36 groups. These results showed that rAg85AB+CP had immunotherapeutic effect on TB, significantly increasing the cellular immune response, and inhibiting the growth of M. tuberculosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

IgG and IgG4 to 91 allergenic molecules in early childhood by route of exposure and current and future IgE sensitization: Results from the Multicentre Allergy Study birth cohort.

PubMed

Schwarz, Alina; Panetta, Valentina; Cappella, Antonio; Hofmaier, Stephanie; Hatzler, Laura; Rohrbach, Alexander; Tsilochristou, Olympia; Bauer, Carl-Peter; Hoffmann, Ute; Forster, Johannes; Zepp, Fred; Schuster, Antje; D'Amelio, Raffaele; Wahn, Ulrich; Keil, Thomas; Lau, Susanne; Matricardi, Paolo Maria

2016-11-01

Studies of a limited number of allergens suggested that nonsensitized children produce IgG responses mainly to foodborne allergens, whereas IgE-sensitized children also produce strong IgG responses to the respective airborne molecules. We sought to systematically test the hypothesis that both the route of exposure and IgE sensitization affect IgG responses to a broad array of allergenic molecules in early childhood. We examined sera of 148 children participating in the Multicentre Allergy Study, a birth cohort born in 1990. IgG to 91 molecules of 42 sources were tested with the ImmunoCAP Solid-Phase Allergen Chip (ISAC; TFS, Uppsala, Sweden). IgE sensitization at age 2 and 7 years was defined by IgE levels of 0.35 kU A /L or greater to 1 or more of 8 or 9 extracts from common allergenic sources, respectively. The prevalence and geometric mean levels of IgG to allergenic molecules in nonsensitized children were lower at age 2 years than in IgE-sensitized children, and they were extremely heterogeneous: highest for animal food (87% ± 13%; 61 ISAC Standardized Units [ISU], [95% CI, 52.5-71.5 ISU]), intermediate for vegetable food (48% ± 27%; 13 ISU [95% CI, 11.2-16.1 ISU]), and lowest for airborne allergens (24% ± 20%; 3 ISU [95% CI, 2.4-3.4 ISU]; P for trend < .001 [for percentages], P for trend < .001 [for levels]). IgG 4 antibodies were infrequent (<5%) and contributed poorly (<3%) to overall IgG antibody levels. IgG responses at age 2 years were slightly more frequent and stronger among children with than in those without IgE sensitization at age 7 years. The children's repertoire of IgG antibodies at 2 years of age to a broad array of animal foodborne, vegetable foodborne, and airborne allergenic molecules is profoundly dependent on the route of allergen exposure and the child's IgE sensitization status and only marginally involves the IgG 4 isotype. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Decreased levels of serum complement C3 and natural killer cells add to the predictive value of total immunoglobulin G for severe infection in heart transplant recipients.

PubMed

Sarmiento, E; del Pozo, N; Gallego, A; Fernández-Yañez, J; Palomo, J; Villa, A; Ruiz, M; Muñoz, P; Rodríguez, C; Rodríguez-Molina, J; Navarro, J; Kotsch, K; Fernandez-Cruz, E; Carbone, J

2012-10-01

Infection remains a source of mortality in heart recipients. We previously reported that post-transplant immunoglobulin G (IgG) quantification can help identify the risk for infection. We assessed whether other standardized parameters of humoral and cellular immunity could prove useful when identifying patients at risk of infection. We prospectively studied 133 heart recipients over a 12-month period. Forty-eight patients had at least one episode of severe infection. An event was defined as an infection requiring intravenous antimicrobial therapy. Cox regression analysis revealed an association between the risk of developing infection and the following: lower IgG2 subclass levels (day 7: relative hazard [RH] 1.71; day 30: RH 1.76), lower IgA levels (day 7: RH 1.61; day 30: RH 1.91), lower complement C3 values (day 7: RH 1.25), lower CD3 absolute counts (day 30: RH 1.10), lower absolute natural killer [NK] cell count (day 7: RH 1.24), and lower IgG concentrations (day 7: RH 1.31; day 30: RH 1.36). Cox regression bivariate analysis revealed that lower day 7 C3 levels, IgG2 concentration, and absolute NK cell count remained significant after adjustment for total IgG levels. Data suggest that early immune monitoring including C3, IgG2, and NK cell testing in addition to IgG concentrations is useful when attempting to identify the risk of infection in heart transplant recipients. © 2012 John Wiley & Sons A/S.

H pylori status and angiogenesis factors in human gastric carcinoma

PubMed Central

Mangia, Anita; Chiriatti, Annalisa; Ranieri, Girolamo; Abbate, Ines; Coviello, Maria; Simone, Giovanni; Zito, Francesco Alfredo; Montemurro, Severino; Rucci, Antonello; Leo, Alfredo Di; Tommasi, Stefania; Berloco, Pasquale; Xu, Jian Ming; Paradiso, Angelo

2006-01-01

AIM: To investigate H pylori expression in gastric cancer patients in relation to primary tumor angiogenic markers, such as microvessel density (MVD), thymidine phosphorylase (TP), vascular endothelial growth factor receptor-1 (VEGF-R1), p53 and circulating VEGF levels. METHODS: Angiogenic markers were analyzed immunohistochemically in 56 primary gastric cancers. H pylori cytotoxin (vacA) and the cytotoxin-associated gene (cagA) amplification were evaluated using PCR assay. Serum H pylori IgG antibodies and serum/plasma circulating VEGF levels were detected in 39 and 38 patients by ELISA, respectively. RESULTS: A total of 69% of patients were positive for circulating IgG antibodies against H pylori. cagA-positive H pylori strains were found in 41% of gastric patients. vacA was found in 50% of patients; s1 strains were more highly expressed among vacA-positive patients. The presence of the s1 strain was significantly associated with cagA (P = 0.0001). MVD was significantly correlated with both tumor VEGF expression (r = 0.361, P = 0.009) and serum VEGF levels (r = -0.347, P = 0.041). Conversely, neither VEGF-R1 expression nor MVD was related to p53 expression. However, H pylori was not related to any angiogenic markers except for the plasma VEGF level (P = 0.026). CONCLUSION: H pylori antigen is related to higher plasma VEGF levels, but not to angiogenic characteristics. It can be hypothesized that the toxic effects of H pylori on angiogenesis occurs in early preclinical disease phase or in long-lasting aggressive infections, but only when high H pylori IgG levels are persistent. PMID:17006982

Distinct features distinguishing IgG4-related disease from multicentric Castleman’s disease

PubMed Central

Sasaki, Takanori; Akiyama, Mitsuhiro; Kaneko, Yuko; Mori, Takehiko; Yasuoka, Hidekata; Suzuki, Katsuya; Yamaoka, Kunihiro; Okamoto, Shinichiro; Takeuchi, Tsutomu

2017-01-01

Objectives Differentiating IgG4-related disease (IgG4-RD) from multicentric Castleman’s disease (MCD) is challenging because both diseases present high serum IgG4. The objective of this study is to clarify the differences in characteristics and identify a clinically useful approach to differentiate these two diseases. Methods Forty-five consecutive patients with untreated active IgG4-RD and 33 patients with MCD were included in this study, who visited our institution from January 2000 to August 2016. The clinical and laboratory findings for the patients of the two diseases were compared. Various combinations of the distinctive findings were evaluated to identify the most efficient differentiating features between IgG4-RD and MCD. Results The levels of serum IgG4 were not different between the two diseases. Orbits, lacrimal glands, salivary glands or pancreas were involved in 88.9% of IgG4-RD cases and only in 3.0% of MCD cases. All MCD cases involved lymph nodes. Atopic history was characteristic for IgG4-RD. The levels of C reactive protein (CRP) with a cut-off of 0.80 mg/dL and IgA with a cut-off of 330 mg/dL were the most distinctive. The combination of ‘Orbits, lacrimal glands, salivary glands or pancreas involvement, atopic history, or non-involvement of lymph node’ and ‘CRP ≤ 0.8 mg/dL or IgA ≤ 330 mg/dL’ yielded the probability of 97.8% in IgG4-RD, while that of 3.0 % in patients with MCD. Conclusions Our study revealed distinct features between IgG4-RD and MCD. Differentiating between the diseases based on those distinct features, including distribution of organ involvement, atopic history, levels of IgA and CRP, was a useful approach. PMID:28959455

469 Levels of IL-4, INF-&GAMMA; Total IGE and IGG4 in Serum of Allergic Children within Areas of Risk of Lead Exposure in Torreon Coahuila, Mexico

PubMed Central

Chavez Villarreal, Karen Giselle; Hernandez, Jahzeel Avila; Goytia Acevedo, Raquel Concepción; Velazquez, Rocio Meza; Guillen, Mario Rivera; Jurado, Michelle Gomez; García-Arenas, Guadalupe; Maravilla-Domínguez, Aurora

2012-01-01

Background There are precedents to suggest that lead exposure may increase the severity of allergic disease in children. In Torreon Coahuila is known the problem of lead contamination and its association with the body burden in children. The aim of this study was to evaluate clinical and biochemical characteristics of allergic disease in children living in areas at risk of lead exposure. Methods We included children between 6 and 11 years old with clinical diagnosis of allergy, who were attending by allergic consultation in the Center of attention Heavy Metals in Torreon, Coahuila, Mexico. Medical evaluation was performed following the diagnostic criteria described by ARIA, Global Initiative for Asthma and the Hanifin and Rajka criteria for atopic dermatitis. Skin tests were applied to 47 common allergens in the region. Were quantified in serum, the levels of IL-4, IFN-γ and IgG4 by ELISA, total IgE levels by chemiluminescence and lead in blood by spectrophotometry AA. Results We present the results of 33 patients (16 girls/17 boys) aged 8 ± 1.38. The main risk factors for allergy were current animal contact (66.7%), past animal exposure (60.6%) and passive smoking (51.5%). The predominant allergy diseases: rhinitis (97%), conjunctivitis (43.8%) and atopic dermatitis (33.3%). The allergens with the higher prevalence of responses were: thickets (91.2%) and grass (88.2%). The average blood lead level was 4.36 μg/dL ± 2.13 and median total IgE 660 IU/mL. We present the analysis of the levels of cytokines, total IgE and IgG4 according to the types of allergy, severity and frequency of the disease. Conclusions IgE levels according to the type of allergic disease, severity and frequency seem to be related to the balance IL-4/INF g. The IgG4 seems to be positively related to total IgE levels in rhinitis, conjunctivitis and dermatitis and negatively with Asthma and other allergies. No association was found between blood lead levels and total IgE.

Safety and antibody response, including antibody persistence for 5 years, after primary vaccination or revaccination with pneumococcal polysaccharide vaccine in middle-aged and older adults.

PubMed

Musher, Daniel M; Manof, Susan B; Liss, Charlie; McFetridge, Richard D; Marchese, Rocio D; Bushnell, Bonnie; Alvarez, Frances; Painter, Carla; Blum, Michael D; Silber, Jeffrey L

2010-02-15

This study assessed antibody levels for 5 years after primary vaccination or revaccination with 23-valent pneumococcal polysaccharide vaccine (PN23). Subjects were enrolled into 4 study groups by age (50-64 or > or = 65 years) and prior vaccination status (no prior vaccination or 1 vaccination 3-5 years previously). Blood was obtained on day 0 (before primary vaccination or revaccination), day 30, day 60, and annually during years 2-5. Levels of immunoglobulin G (IgG) to 8 vaccine serotypes were measured by enzyme-linked immunosorbent assay. Of 1008 enrolled subjects, 551 completed year 5. For each serotype and age group, baseline geometric mean concentrations (GMCs) of IgG were higher in revaccination than primary vaccination subjects. Primary vaccination or revaccination with PN23 induced significant increases in levels of antibody to all serotypes tested. Although day 30 and 60 antibody levels tended to be modestly lower after revaccination, study groups had similar GMCs at later time points. For serotypes 4, 6B, 8, 9V, 12F, 14, and 23F, GMCs during years 2-5 after primary vaccination or revaccination remained higher than in vaccine-naive persons. Levels of antibody to serotype 3 returned to baseline by year 2. Both primary vaccination and revaccination with PN23 induce antibody responses that persist during 5 years of observation.

The dynamic and clinical significance of autoantibodies and immunoglobulins in liver transplant recipients.

PubMed

Stanca, Carmen M; Aloman, Costica; Fiel, Maria Isabel; Raja, Kaiser; Uskudar, Oguz; Florman, Sander; Schiano, Thomas D

2016-03-01

Little is known about autoantibody pattern in liver transplantation (LT). The aim of the study was to examine autoantibodies (AAB) and immunoglobulins in patients with end-stage liver disease before and after LT. Patients with LT who underwent post-LT biopsies between 10/2008 and 8/2011 were enrolled. AAB were assessed at the time of LT and liver biopsy. Demographics, serum immunoglobulins, AAB, and liver histology (explant, post-LT biopsies) were analyzed. Two hundred and twenty patients (M/F 143/77; age at LT 54 (19-73)) were included; AAB and immunoglobulins were evaluated in 76 patients. Length of follow-up from LT was 285 (30-1462) days. Sixty-one percent of patients had hepatitis C (HCV); 83% developed recurrent HCV. A significant decrease in IgG, IgA, IgM (p < 0.001 each), anticardiolipin antibodies IgG and IgM (p = 0.02), and beta-2 microglobulin (p = 0.004) was observed post-LT. HCV patients had higher IgG (p = 0.005), rheumatoid factor (p = 0.044) before LT; elevated IgM was associated with increased inflammation in the explant (p = 0.007). Lower IgG levels and antismooth muscle antibodies were present before LT in a higher percentage in patients who would develop recurrent HCV (p = 0.004, p = 0.077, respectively). In conclusion, AAB change significantly after LT and have a different pattern in HCV. Some immunological markers are associated with HCV recurrence and advanced inflammation on explant. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Biocompatible chitosan nanoparticles as an efficient delivery vehicle for Mycobacterium tuberculosis lipids to induce potent cytokines and antibody response through activation of γδ T cells in mice

NASA Astrophysics Data System (ADS)

Das, Ishani; Padhi, Avinash; Mukherjee, Sitabja; Dash, Debi P.; Kar, Santosh; Sonawane, Avinash

2017-04-01

The activation of cell-mediated and humoral immune responses to Mycobacterium tuberculosis (Mtb) is critical for protection against the pathogen and nanoparticle-mediated delivery of antigens is a more potent way to induce different immune responses. Herein, we show that mice immunized with Mtb lipid-bound chitosan nanoparticles (NPs) induce secretion of prominent type-1 T-helper (Th-1) and type-2 T-helper (Th-2) cytokines in lymph node and spleen cells, and also induces significantly higher levels of IgG, IgG1, IgG2 and IgM in comparison to control mice. Furthermore, significantly enhanced γδ-T-cell activation was observed in lymph node cells isolated from mice immunized with Mtb lipid-coated chitosan NPs as compared to mice immunized with chitosan NPs alone or Mtb lipid liposomes. In comparison to CD8+ cells, significantly higher numbers of CD4+ cells were present in both the lymph node and spleen cells isolated from mice immunized with Mtb lipid-coated chitosan NPs. In conclusion, this study represents a promising new strategy for the efficient delivery of Mtb lipids using chitosan NPs to trigger an enhanced cell-mediated and antibody response against Mtb lipids.

High natural antibody titers of indigenous chickens are related with increased hazard in confinement.

PubMed

Wondmeneh, E; Van Arendonk, J A M; Van der Waaij, E H; Ducro, B J; Parmentier, H K

2015-07-01

Natural antibody (NAb) levels and survival rates were evaluated in 4 breeds of laying hens in Ethiopia: indigenous, improved indigenous, exotic layer, and crossbred. Titers of NAb isotypes IgG and IgM binding keyhole limpet hemocyanin (KLH) in serum were measured at 20, 26, 35, and 45 wk age. Repeated-measure ANOVA showed that IgG and IgM levels vary with time within each breed (P < 0.05). Indigenous chickens had significantly (P < 0.05) higher NAb levels at all ages. The Cox proportional hazard analysis showed increased hazard with increased levels of NAbs in the exotic layers (P < 0.05). However, the reduced hazards with increased levels of NAbs were not significant in the improved indigenous and crossbred chickens. Indigenous chickens showed increased hazard with increasing levels of NAb (P > 0.05). We concluded that not only the NAb levels but also the effect of Nabs on survival vary between indigenous and improved breeds. The results indicate that NAb levels are associated with survival in elite (improved) breeds, but are associated with increased hazard in indigenous chickens. © The Author 2015. Published by Oxford University Press on behalf of Poultry Science Association.

Quantification of anti-Leishmania antibodies in saliva of dogs.

PubMed

Cantos-Barreda, Ana; Escribano, Damián; Bernal, Luis J; Cerón, José J; Martínez-Subiela, Silvia

2017-08-15

Detection of serum anti-Leishmania antibodies by quantitative or qualitative techniques has been the most used method to diagnose Canine Leishmaniosis (CanL). Nevertheless, saliva may represent an alternative to blood because it is easy to collect, painless and non-invasive in comparison with serum. In this study, two time-resolved immunofluorometric assays (TR-IFMAs) for quantification of anti-Leishmania IgG2 and IgA antibodies in saliva were developed and validated and their ability to distinguish Leishmania-seronegative from seropositive dogs was evaluated. The analytical study was performed by evaluation of assay precision, sensitivity and accuracy. In addition, serum from 48 dogs (21 Leishmania-seropositive and 27 Leishmania-seronegative) were analyzed by TR-IFMAs. The assays were precise, with an intra- and inter-assay coefficients of variation lower than 11%, and showed high level of accuracy, as determined by linearity under dilution (R 2 =0.99) and recovery tests (>88.60%). Anti-Leishmania IgG2 antibodies in saliva were significantly higher in the seropositive group compared with the seronegative (p<0.0001), whereas no significant differences for anti-Leishmania IgA antibodies between both groups were observed. Furthermore, TR-IFMA for quantification of anti-Leishmania IgG2 antibodies in saliva showed higher differences between seropositive and seronegative dogs than the commercial assay used in serum. In conclusion, TR-IFMAs developed may be used to quantify anti-Leishmania IgG2 and IgA antibodies in canine saliva with an adequate precision, analytical sensitivity and accuracy. Quantification of anti-Leishmania IgG2 antibodies in saliva could be potentially used to evaluate the humoral response in CanL. However, IgA in saliva seemed not to have diagnostic value for this disease. For future studies, it would be desirable to evaluate the ability of the IgG2 assay to detect dogs with subclinical disease or with low antibody titers in serum and also to study the antibodies behaviour in saliva during the treatment of CanL. Copyright © 2017 Elsevier B.V. All rights reserved.

Intradermal Delivery of Antigens Enhances Specific IgG and Diminishes IgE Production: Potential Use for Vaccination and Allergy Immunotherapy

PubMed Central

Yasuda, Takuwa; Ura, Takehiro; Taniguchi, Masaru; Yoshida, Hisahiro

2016-01-01

Skin is protected by a tough but flexible multilayered barrier and is a front line for immune responses against invading particles. For many years now, skin has been a tissue where certain vaccines are injected for the prevention of infectious disease, however, the detailed mechanisms of the skin immune response are not yet well understood. Using thin and small injection needles, we carefully injected OVA into a restricted region of mouse skin, i.e., intradermal (ID), and examined the antibody response in comparison with subcutaneous (SC) injection or epicutaneous patch administration of OVA. Epicutaneous patches induced a high IgE response against OVA, but IgG production was low. High IgG production was induced by both ID and SC injection, moreover, ID injection induced higher IgG production without any adjutants. Furthermore, OVA-specific IgE production was diminished by ID injection. We found that ID injection could efficiently stimulate skin resident DCs, drive Th1-biased conditions and diminish IgE production. The ID injection response was regulated by Langerin+ dermal DCs, because OVA was taken up mainly by these cells and, after transiently deleting them, the IgE response was no longer diminished and IgG1 production was enhanced. We also tested whether ID injection might be an effective allergy treatment by attempting to inhibit ongoing IgE production in mice with experimentally induced high serum IgE levels. Multiple ID injections of OVA were shown to prevent elevation of serum OVA-specific IgE after repeated allergen challenge. In contrast, SC OVA injection could only transiently inhibit the OVA-specific IgE production. These findings indicated that ID injection results in higher induction of antigen-specific IgG, and thus may be useful for vaccine delivery with little or no adjuvant components. Moreover, the observed diminishment of IgE and induction of Th1-biased immune responses suggest that ID may be a useful injection route for allergy immunotherapy. PMID:27973543

Molecular and functional characterization of FcγRIIIb receptor-ligand interaction: implications for neutrophil mediated immune mechanisms in malaria.

PubMed

Simtong, Piyapong; Romphruk, Amornrat V; Traum, Annalena; Burg-Roderfeld, Monika; Bein, Gregor; Jakubowski, Konstantin; Dominik, Andreas; Theisen, Michael; Kana, Ikhlaq Hussain; Sachs, Ulrich J; Santoso, Sentot

2018-05-21

The Fcγ receptor IIIb (FcγRIIIb) is a low-affinity receptor of IgG and is essential in neutrophil mediated effector functions. Different allelic forms of FcγRIIIb carrying human neutrophil antigen (HNA-1a, -1b, -1c and -1d) have been identified. Here, we have generated stable transfected HEK293 cell lines expressing HNA-1aa, -1bb, and -1bc. Of these, cells expressing HNA-1bc interacted significantly stronger (2.277 versus 0.743) with human IgG than cells expressing the HNA-1aa or -1bb alloforms. The higher affinity of IgG towards the HNA-1c alloform was confirmed using neutrophils derived from German blood donors. Neutrophils from HNA-1abc phenotyped individuals bound IgG significantly stronger (1.825 versus 0.903) than neutrophils from HNA-1ab typed individuals. These findings were confirmed by the SPR analysis demonstrating that recombinant HNA-1bc had a higher affinity (KD 7.24 x 10 -6 M) than recombinant HNA-1bb (KD 1.15 x 10 -5 M) against normal IgG. Finally, we demonstrated that Plasmodium falciparum merozoites opsonized with human IgG affinity purified against P. falciparum Glutamate rich protein (GLURP) enhanced stronger ROS emission in neutrophils obtained from HNA-1abc donors compared to neutrophils from HNA-1ab donors. Collectively, these results indicate that the amino acid substitution Ala 78 Asp resulting in the HNA-1c allotype leads to higher affinity towards human IgG, enhancement of neutrophil activation and possibly effective clearance of malaria by intracellular ROS. Copyright © 2018 American Society for Microbiology.

Air pollution and children: neural and tight junction antibodies and combustion metals, the role of barrier breakdown and brain immunity in neurodegeneration.

PubMed

Calderón-Garcidueñas, Lilian; Vojdani, Aristo; Blaurock-Busch, Eleonore; Busch, Yvette; Friedle, Albrecht; Franco-Lira, Maricela; Sarathi-Mukherjee, Partha; Martínez-Aguirre, Xavier; Park, Su-Bin; Torres-Jardón, Ricardo; D'Angiulli, Amedeo

2015-01-01

Millions of children are exposed to concentrations of air pollutants, including fine particulate matter (PM2.5), above safety standards. In the Mexico City Metropolitan Area (MCMA) megacity, children show an early brain imbalance in oxidative stress, inflammation, innate and adaptive immune response-associated genes, and blood-brain barrier breakdown. We investigated serum and cerebrospinal fluid (CSF) antibodies to neural and tight junction proteins and environmental pollutants in 139 children ages 11.91 ± 4.2 y with high versus low air pollution exposures. We also measured metals in serum and CSF. MCMA children showed significantly higher serum actin IgG, occludin/zonulin 1 IgA, IgG, myelin oligodendrocyte glycoprotein IgG and IgM (p < 0.01), myelin basic protein IgA and IgG, S-100 IgG and IgM, and cerebellar IgG (p < 0.001). Serum IgG antibodies to formaldehyde, benzene, and bisphenol A, and concentrations of Ni and Cd were significantly higher in exposed children (p < 0.001). CSF MBP antibodies and nickel concentrations were higher in MCMA children (p = 0.03). Air pollution exposure damages epithelial and endothelial barriers and is a robust trigger of tight junction and neural antibodies. Cryptic 'self' tight junction antigens can trigger an autoimmune response potentially contributing to the neuroinflammatory and Alzheimer and Parkinson's pathology hallmarks present in megacity children. The major factor determining the impact of neural antibodies is the integrity of the blood-brain barrier. Defining the air pollution linkage of the brain/immune system interactions and damage to physical and immunological barriers with short and long term neural detrimental effects to children's brains ought to be of pressing importance for public health.

Role of B7 costimulatory molecules in immune responses and T-helper cell differentiation in response to recombinant HagB from Porphyromonas gingivalis.

PubMed

Zhang, Ping; Martin, Michael; Yang, Qiu-Bo; Michalek, Suzanne M; Katz, Jannet

2004-02-01

In addition to antigen-specific signals mediated through the T-cell receptor, T cells also require antigen nonspecific costimulation for activation. The B7 family of molecules on antigen-presenting cells, which include B7-1 (CD80) and B7-2 (CD86), play important roles in providing costimulatory signals required for development of antigen-specific immune responses. Hemagglutinin B (HagB) is a nonfimbrial adhesin of the periodontopathic microorganism Porphyromonas gingivalis and is thought to be involved in the attachment of the bacterium to host tissues. However, the immune mechanisms involved in responses to HagB and their roles in pathogenesis have yet to be elucidated. Therefore, the purpose of this study was to determine the role of B7 costimulatory molecules on T-helper-cell differentiation for the induction of immune responses to HagB. Mice deficient in either or both of the costimulatory molecules B7-1 and B7-2 were used to explore their role in immune responses to HagB after subcutaneous immunization. B7-1(-/-) mice had levels of immunoglobulin G (IgG) anti-HagB antibody activity in serum similar to those of wild-type mice, whereas lower serum IgG anti-HagB antibody responses were seen in B7-2(-/-) mice. Moreover, significantly lower numbers of IgG antibody-secreting cells and lower levels of CD4(+)-T-cell proliferation were observed in B7-2(-/-) mice compared to wild-type mice. No serum IgG response to HagB was detected in B7-1/B7-2(-/-) mice. Analysis of the subclass of the serum IgG responses and the cytokines induced in response to HagB revealed that B7-2(-/-) mice had significantly lower IgG1 and higher IgG2a anti-HagB antibody responses compared to wild-type mice. The B7-2(-/-) mice also had significantly reduced levels of interleukin-4 (IL-4) and IL-5 and enhanced level of gamma interferon. Furthermore, assessment of B7-1 and B7-2 expression on B cells and macrophages derived from wild-type BALB/c mice after in vitro stimulation with HagB revealed a predominant upregulation in the expression of the B7-2 costimulatory molecule on B cells and macrophages. Essentially no change was seen in the expression of B7-1. Taken together, these results suggest a critical role for B7, especially B7-2, for the preferential induction of a Th2-like response to HagB.

Evaluation of IgG4+ Plasma Cell Infiltration in Patients with Systemic Plasmacytosis and Other Plasma Cell-infiltrating Skin Diseases.

PubMed

Takeoka, Shintaro; Kamata, Masahiro; Hau, Carren Sy; Tateishi, Mihoko; Fukaya, Saki; Hayashi, Kotaro; Fukuyasu, Atsuko; Tanaka, Takamitsu; Ishikawa, Takeko; Ohnishi, Takamitsu; Sasajima, Yuko; Watanabe, Shinichi; Tada, Yayoi

2018-04-27

Systemic plasmacytosis is a rare skin disorder characterized by marked infiltration of plasma cells in the dermis. IgG4-related disease is pathologically characterized by lymphoplasmacytic infiltration rich in IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis, accompanied by elevated levels of serum IgG4. Reports of cases of systemic plasmacytosis with abundant infiltration of IgG4+ plasma cells has led to discussion about the relationship between systemic plasmacytosis and IgG4-related disease. This study examined IgG4+/IgG+ plasma cell ratios in 4 patients with systemic plasmacytosis and 12 patients with other skin diseases that show marked infiltration of plasma cells. Furthermore, we examined whether these cases met one of the pathological diagnostic criteria for IgG4-related disease (i.e. IgG4+/IgG plasma cells ratio of over 40%). Only one out of 4 patients with systemic plasmacytosis met the criterion. These results suggest that systemic plasmacytosis and IgG4-related disease are distinct diseases.

Sin Nombre virus-specific immunoglobulin M and G kinetics in hantavirus pulmonary syndrome and the role played by serologic responses in predicting disease outcome.

PubMed

MacNeil, Adam; Comer, James A; Ksiazek, Thomas G; Rollin, Pierre E

2010-07-15

Sin Nombre virus (SNV) is the primary cause of hantavirus pulmonary syndrome (HPS) in the United States. Although other studies have demonstrated a possible association between neutralizing antibody titers and the severity of HPS, the exact nature of serologic responses and their association with outcomes have not been fully characterized. We examined immunoglobulin M (IgM) and immunoglobulin G (IgG) serologic responses in 94 clinical samples from 81 patients with confirmed HPS. We further compared a subset of 31 patients with fatal HPS and 20 surviving patients for whom samples were available within a week after the onset of HPS. SNV-specific IgM antibodies displayed a trend suggesting an early peak, whereas IgG antibody values peaked later. Among individuals with samples from the first week after the onset of HPS, all surviving patients had SNV-specific IgG responses, compared with <50% of patients with fatal HPS, and the distribution of IgG responses was significantly higher in surviving patients. Production of SNV-specific IgM antibodies occurs early during the clinical course of HPS, whereas production of IgG antibodies may be more protracted. The presence and overall distribution of higher IgG antibody titers in surviving patients with HPS suggests that production of SNV-specific IgG may be a strong predictor of favorable outcomes.

Anti-pertussis antibody kinetics following DTaP-IPV booster vaccination in Norwegian children 7-8 years of age.

PubMed

Aase, Audun; Herstad, Tove Karin; Jørgensen, Silje Bakken; Leegaard, Truls Michael; Berbers, Guy; Steinbakk, Martin; Aaberge, Ingeborg

2014-10-14

At the age of 7-8 years a booster of diphtheria, tetanus, acellular pertussis and polio vaccine is recommended for children in Norway. In this cross-sectional study we have analysed the antibody levels against pertussis vaccine antigens in sera from 498 children aged 6-12 years. The purposes of this study were to investigate the duration of the booster response against the pertussis vaccine antigens pertussis toxin (PT) and filamentous haemagglutinin (FHA); to determine the presence of high levels of pertussis antibodies in absence of recent vaccination; and to analyse how booster immunisation may interfere with the serological pertussis diagnostics. Prior to the booster the IgG antibody levels against PT revealed a geometric mean of 7.3IU/ml. After the booster the geometric mean peak anti-PT IgG response reached to 45.6IU/ml, followed by a steady decline in antibody levels over the next few years. The IgG anti-FHA levels followed the anti-PT IgG profiles. Three years after the booster the geometric mean IgG levels were only slightly above pre-booster levels. Prior to the booster 44% of the sera contained ≤5IU/ml of anti-PT IgG compared to18% 3 years after and 30% 4 years after the booster. When recently vaccinated children were excluded, 6.2% of the children had anti-PT IgG levels above 50IU/ml which may indicate pertussis infection within the last 2 years. This study indicates that the currently used acellular pertussis vaccines induce moderate immune responses to the pertussis antigens and that the antibodies wane within few years after the booster. This lack of sustained immune response may partly be responsible for the increased number of pertussis cases observed in this age group during the last years. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Improved Carbohydrate Metabolism After Bariatric Surgery Raises Antioxidized LDL Antibody Levels in Morbidly Obese Patients

PubMed Central

Garrido-Sánchez, Lourdes; García-Almeida, Jose M.; García-Serrano, Sara; Cardona, Isabel; García-Arnes, Juan; Soriguer, Federico; Tinahones, Francisco J.; García-Fuentes, Eduardo

2008-01-01

OBJECTIVE—Antioxidized LDL (anti-oxLDL) antibodies have recently been suggested to be protective against the development of diabetes. We measured the changes in anti-oxLDL antibody levels in the inverse situation of improvement in carbohydrate metabolism. RESEARCH DESIGN AND METHODS—The study was undertaken in 73 morbidly obese individuals, 21 of whom had type 2 diabetes, before and 7 months after they underwent bariatric surgery and in 11 healthy, nonobese individuals. Measurements were made of the area under the curve of glucose (AUCGlu) by an intravenous glucose tolerance test and of oxidized LDL (oxLDL) and IgG and IgM anti-oxLDL antibodies. RESULTS—The morbidly obese patients with diabetes had significantly higher levels of oxLDL compared with the morbidly obese patients with normal fasting glucose and the control subjects and significantly lower levels of IgM anti-oxLDL antibodies. An inverse correlation was found between the levels of oxLDL and IgM anti-oxLDL antibodies (r = −0.352, P = 0.012). Although the levels of IgG and IgM anti-oxLDL antibodies rose after surgery, this increase was only significant in the diabetic patients, who experienced an improvement in their metabolic profile. Different multiple linear regression models showed that the AUCGlu was the main factor explaining the behavior of the levels of oxLDL and anti-oxLDL antibodies. CONCLUSIONS—We found a close association between carbohydrate metabolism and IgM anti-oxLDL antibodies, which were significantly reduced in the morbidly obese patients with diabetes. The improvement in carbohydrate metabolism after bariatric surgery led to a significant increase in the levels of IgG and IgM anti-oxLDL antibodies. PMID:18835956

The IgG2a antibody response to thyroglobulin is linked to the Igh locus in mouse.

PubMed

Kuppers, R C; Epstein, L D; Outschoorn, I M; Rose, N R

1994-01-01

The IgG-subclass usage by several strains of mice in the response to immunization with mouse thyroglobulin (mTg) was examined in the experimental autoimmune thyroiditis model. While the subclass usage by most mouse strains was similar, the Ighb allotype-bearing mice consistently produced lower IgG2a levels to mTg. Using CBA-Ighb congenic and recombinant inbred strains of mice, the lower level of IgG2a in the Ighb mouse was mapped to the Igh locus. The regulation of IgG2a appeared to be cis controlled, as the CBA x C57BL/6F1 mouse also produced reduced IgG2a of the Ighb (B6) allotype but not of the Ighj (CBA) allotype.

Absolute Quantitation of Glycoforms of Two Human IgG Subclasses Using Synthetic Fc Peptides and Glycopeptides

NASA Astrophysics Data System (ADS)

Roy, Rini; Ang, Evelyn; Komatsu, Emy; Domalaon, Ronald; Bosseboeuf, Adrien; Harb, Jean; Hermouet, Sylvie; Krokhin, Oleg; Schweizer, Frank; Perreault, Hélène

2018-05-01

Immunoglobulins, such as immunoglobulin G (IgG), are of prime importance in the immune system. Polyclonal human IgG comprises four subclasses, of which IgG1 and IgG2 are the most abundant in healthy individuals. In an effort to develop an absolute MALDI-ToF-MS quantitative method for these subclasses and their Fc N-glycoforms, (glyco)peptides were synthesized using a solid-phase approach and used as internal standards. Tryptic digest glycopeptides from monoclonal IgG1 and IgG2 samples were first quantified using EEQYN(GlcNAc)STYR and EEQFN(GlcNAc)STFR standards, respectively. For IgG1, a similar glycopeptide where tyrosine (Y) was isotopically labelled was used to quantify monoclonal IgG1 that had been treated with the enzyme Endo-F2, i.e., yielding tryptic glycopeptide EEQYN(GlcNAc)STYR. The next step was to quantify single subclasses within polyclonal human IgG samples. Although ion abundances in the MALDI spectra often showed higher signals for IgG2 than IgG1, depending on the spotting solvent used, determination of amounts using the newly developed quantitative method allowed to obtain accurate concentrations where IgG1 species were predominant. It was observed that simultaneous analysis of IgG1 and IgG2 yielded non-quantitative results and that more success was obtained when subclasses were quantified one by one. More experiments served to assess the respective extraction and ionization efficiencies of EEQYNSTYR/EEQFNSTFR and EEQYN(GlcNAc)STYR/EEQFN(GlcNAc)STFR mixtures under different solvent and concentration conditions.

Comparative evaluation of serum and salivary immunoglobulin G and A levels with total serum protein in oral submucous fibrosis patients: A case control study.

PubMed

Kandasamy, M; Jaisanghar, N; Austin, Ravi David; Srivastava, Kumar Chandan; Anusuya, G Sai; Anisa, N

2016-10-01

The objective of this study is to estimate and compare the serum and salivary immunoglobulin G and A (IgG, IgA) levels in various stages of oral submucous fibrosis (OSMF) patients and relate it to total serum protein (TSP) and hemoglobin (Hb) levels. The sample for the present study comprised a total of 20 healthy controls, 20 OSMF patients. About 5 ml of blood and 2 ml of saliva were collected. Quantitative analysis of serum and salivary IgG, IgA was done by turbidometric immunoassay. TSP and Hb were estimated by Biuret and cyanmethemoglobin methods, respectively. Serum and salivary IgA and IgG levels were statistically significantly increased ( P < 0.001) in OSMF patients when compared to controls. Also serum and salivary IgG and IgA levels showed significantly increased ( P < 0.01) in all the three staging of OSMF when compared to control group. Hb levels and TSP levels were significantly decreased ( P < 0.001) in OSMF patients when compared to controls. One-way ANOVA, Pearson's correlation, and unpaired t -test were used for statistical analysis. The elevated levels of IgG and IgA are also in favor of polygammapathy, which are nonspecific and nondiagnostic objective reflections of an underlying disease. Decreased TSP is a result of host response and Hb, acts as an indicator of nutritional status plays an important role. It is also observed from the present study that the severity of OSMF was directly proportional to the estimated elevated levels of the major IgG and IgA. A need is also felt for the knowledge of immunoprofile estimation in etiology and pathogenesis that would prove a great asset in the proper assessment of this condition.

Increased levels of anti-non-Gal IgG following pig-to-baboon bone marrow transplantation correlate with failure of engraftment

PubMed Central

Liang, Fan; Wamala, Isaac; Scalea, Joseph; Tena, Aseda; Cormack, Taylor; Pratts, Shannon; Struuck, Raimon Duran; Elias, Nahel; Hertl, Martin; Huang, Christene A.; Sachs, David H.

2013-01-01

Background The development of genetically modified pigs which lack the expression of alpha 1–3 galactosyl transferase, (GalT-KO pigs) has facilitated the xenogeneic transplantation of porcine organs and tissues into primates by avoiding hyperacute rejection due to pre-existing antibodies against the Gal epitope. However, antibodies against other antigens (anti-non-Gal antibodies), are found at varying levels in the pre-transplant sera of most primates. We have previously found that baboons with high levels of pre-transplant anti-non-Gal IgG, conditioned with a non-myeloablative conditioning regimen, failed to engraft following pig-to-baboon bone marrow transplantation [8]. Two baboons with low levels of pre-transplant anti-non-Gal IgG, conditioned with the same regimen, showed porcine bone marrow progenitors at 28 days following transplantation, suggesting engraftment. These baboons also showed evidence of donor-specific hypo-responsiveness. This observation led us to investigate the hypothesis that selecting for baboon recipients with low pre-transplant anti-non-Gal IgG levels might improve engraftment levels following GalT-KO pig-to-baboon bone marrow transplantation. Methods Five baboons, with low pre-transplant anti-non-Gal IgG levels, received transplantation of bone marrow cells (1–5 × 10^9/kg of recipient weight) from GalT-KO pigs. They received a non-myeloablative conditioning regimen consisting of low-dose total body irradiation (150cGy), thymic irradiation (700cGy), anti-thymocyte globulin (ATG) and tacrolimus. In addition, two baboons received Rituximab and Bortezomib (Velcade) treatment as well as extra-corporeal immunoadsorption using GalT-KO pig livers. Bone marrow engraftment was assessed by porcine-specific PCR on colony forming units (CFU) of day 28 bone marrow aspirates. Anti-non-Gal antibody levels were assessed by serum binding towards GalT-KO PBMC using flow cytometry (FACS). Peripheral macro-chimerism was measured by FACS using pig and baboon-specific antibodies and baboon anti-pig cellular responses were assessed by mixed lymphocyte reactions (MLR). Results As previously reported, two of five baboons demonstrated detectable bone marrow engraftment at four weeks after transplantation. Engraftment was associated with lack of an increase in anti–non-Gal IgG levels as well as cellular hypo-responsiveness towards pig. Three subsequent baboons with similarly low levels of pre-existing anti-non-Gal IgG showed no engraftment and an increase in anti-non-Gal IgG antibody levels following transplantation. Peripheral macrochimerism was only seen for a few days following transplantation regardless of antibody development. Conclusions Selecting for baboon recipients with low levels of pre-transplant anti-non-Gal IgG did not ensure bone marrow engraftment. Failure to engraft was associated with an increase in anti-non-Gal IgG levels following transplantation. These results suggest that anti-non-Gal-IgG is likely involved in early bone marrow rejection and that successful strategies for combating anti-non-Gal IgG development may allow better engraftment. Since engraftment was only low and transient regardless of antibody development, innate immune, or species compatibility mechanisms will likely also need to be addressed in order to achieve long term engraftment. PMID:24289469

Different Dynamics for IgG and IgA Memory B Cells in Adolescents following a Meningococcal Serogroup C Tetanus Toxoid Conjugate Booster Vaccination Nine Years after Priming: A Role for Priming Age?

PubMed Central

Stoof, Susanne P.; Buisman, Anne-Marie; van Rooijen, Debbie M.; Boonacker, Rianne; van der Klis, Fiona R. M.; Sanders, Elisabeth A. M.; Berbers, Guy A. M.

2015-01-01

Background Antibody levels wane rapidly after Meningococcal serogroup C conjugate (MenCC) vaccination in young children, rendering the need for an adolescent booster dose. It is not clear whether circulating memory B cells are associated with persistence of MenC-specific antibody levels. Methods Measurement of MenC-specific IgG and IgA memory B cells and levels of serum and salivary MenC-specific IgG and IgA in healthy 10-, 12- and 15-year-olds prior to and one month and one year after a MenCC booster vaccination. All participants had received a primary MenCC vaccination nine years earlier. Results The number of circulating MenC-specific IgG memory B cells prior to booster was low and not predictive for MenC-specific IgG responses in serum or saliva post-booster, whereas the number of MenC-specific IgA memory B cells pre-booster positively correlated with MenC-specific IgA levels in saliva post-booster (R = 0.5, P<0.05). The booster induced a clear increase in the number of MenC-specific IgG and IgA memory B cells. The number of MenC-PS-specific IgG memory B cells at 1 month post-booster was highest in the 12-year-olds. The number of MenC-specific memory B cells at one month post-booster showed no correlation with the rate of MenC-specific antibody decay throughout the first year post-booster. Conclusions Circulating MenC-specific IgA memory B cells correlate with IgA responses in saliva, whereas circulating MenC-specific IgG memory B cells are not predictive for MenC-specific IgG responses in serum or saliva. Our results are suggestive for age-dependent differences in pre-existing memory against MenC. PMID:26458006

Different Dynamics for IgG and IgA Memory B Cells in Adolescents following a Meningococcal Serogroup C Tetanus Toxoid Conjugate Booster Vaccination Nine Years after Priming: A Role for Priming Age?

PubMed

Stoof, Susanne P; Buisman, Anne-Marie; van Rooijen, Debbie M; Boonacker, Rianne; van der Klis, Fiona R M; Sanders, Elisabeth A M; Berbers, Guy A M

2015-01-01

Antibody levels wane rapidly after Meningococcal serogroup C conjugate (MenCC) vaccination in young children, rendering the need for an adolescent booster dose. It is not clear whether circulating memory B cells are associated with persistence of MenC-specific antibody levels. Measurement of MenC-specific IgG and IgA memory B cells and levels of serum and salivary MenC-specific IgG and IgA in healthy 10-, 12- and 15-year-olds prior to and one month and one year after a MenCC booster vaccination. All participants had received a primary MenCC vaccination nine years earlier. The number of circulating MenC-specific IgG memory B cells prior to booster was low and not predictive for MenC-specific IgG responses in serum or saliva post-booster, whereas the number of MenC-specific IgA memory B cells pre-booster positively correlated with MenC-specific IgA levels in saliva post-booster (R = 0.5, P<0.05). The booster induced a clear increase in the number of MenC-specific IgG and IgA memory B cells. The number of MenC-PS-specific IgG memory B cells at 1 month post-booster was highest in the 12-year-olds. The number of MenC-specific memory B cells at one month post-booster showed no correlation with the rate of MenC-specific antibody decay throughout the first year post-booster. Circulating MenC-specific IgA memory B cells correlate with IgA responses in saliva, whereas circulating MenC-specific IgG memory B cells are not predictive for MenC-specific IgG responses in serum or saliva. Our results are suggestive for age-dependent differences in pre-existing memory against MenC.

An Immunoglobulin G1 Monoclonal Antibody Highly Specific to the Wall of Cryptosporidium Oocysts

PubMed Central

Weir, C.; Vesey, G.; Slade, M.; Ferrari, B.; Veal, D. A.; Williams, K.

2000-01-01

The detection of Cryptosporidium oocysts in drinking water is critically dependent on the quality of immunofluorescent reagents. Experiments were performed to develop a method for producing highly specific antibodies to Cryptosporidium oocysts that can be used for water testing. BALB/c mice were immunized with six different antigen preparations and monitored for immunoglobulin G (IgG) and IgM responses to the surface of Cryptosporidium oocysts. One group of mice received purified oocyst walls, a second group received a soluble protein preparation extracted from the outside of the oocyst wall, and the third group received whole inactivated oocysts. Three additional groups were immunized with sequentially prepared oocyst extracts to provide for a comparison of the immune response. Mice injected with the soluble protein extract demonstrated an IgG response to oocysts surface that was not seen in the whole-oocyst group. Mice injected with whole oocysts showed an IgM response only, while mice injected with purified oocyst walls showed little increase in IgM or IgG levels. Of the additional reported preparations only one, BME (2-mercaptoethanol treated), produced a weak IgM response to the oocyst wall. A mouse from the soluble oocyst extract group yielding a high IgG response was utilized to produce a highly specific IgG1 monoclonal antibody (Cry104) specific to the oocyst surface. Comparative flow cytometric analysis indicated that Cry104 has a higher avidity and specificity to oocysts in water concentrates than other commercially available antibodies. PMID:10973448

Amino acid and glucose metabolism in fed-batch CHO cell culture affects antibody production and glycosylation.

PubMed

Fan, Yuzhou; Jimenez Del Val, Ioscani; Müller, Christian; Wagtberg Sen, Jette; Rasmussen, Søren Kofoed; Kontoravdi, Cleo; Weilguny, Dietmar; Andersen, Mikael Rørdam

2015-03-01

Fed-batch Chinese hamster ovary (CHO) cell culture is the most commonly used process for IgG production in the biopharmaceutical industry. Amino acid and glucose consumption, cell growth, metabolism, antibody titer, and N-glycosylation patterns are always the major concerns during upstream process optimization, especially media optimization. Gaining knowledge on their interrelations could provide insight for obtaining higher immunoglobulin G (IgG) titer and better controlling glycosylation-related product quality. In this work, different fed-batch processes with two chemically defined proprietary media and feeds were studied using two IgG-producing cell lines. Our results indicate that the balance of glucose and amino acid concentration in the culture is important for cell growth, IgG titer and N-glycosylation. Accordingly, the ideal fate of glucose and amino acids in the culture could be mainly towards energy and recombinant product, respectively. Accumulation of by-products such as NH4(+) and lactate as a consequence of unbalanced nutrient supply to cell activities inhibits cell growth. The levels of Leu and Arg in the culture, which relate to cell growth and IgG productivity, need to be well controlled. Amino acids with the highest consumption rates correlate with the most abundant amino acids present in the produced IgG, and thus require sufficient availability during culture. Case-by-case analysis is necessary for understanding the effect of media and process optimization on glycosylation. We found that in certain cases the presence of Man5 glycan can be linked to limitation of UDP-GlcNAc biosynthesis as a result of insufficient extracellular Gln. However, under different culture conditions, high Man5 levels can also result from low α-1,3-mannosyl-glycoprotein 2-β-N-acetylglucosaminyltransferase (GnTI) and UDP-GlcNAc transporter activities, which may be attributed to high level of NH4+ in the cell culture. Furthermore, galactosylation of the mAb Fc glycans was found to be limited by UDP-Gal biosynthesis, which was observed to be both cell line and cultivation condition-dependent. Extracellular glucose and glutamine concentrations and uptake rates were positively correlated with intracellular UDP-Gal availability. All these findings are important for optimization of fed-batch culture for improving IgG production and directing glycosylation quality. © 2014 Wiley Periodicals, Inc.

Toxoplasma gondii Infection and Mixed Anxiety and Depressive Disorder: A Case-Control Seroprevalence Study in Durango, Mexico

PubMed Central

Alvarado-Esquivel, Cosme; Sanchez-Anguiano, Luis Francisco; Hernandez-Tinoco, Jesus; Berumen-Segovia, Luis Omar; Torres-Prieto, Yazmin Elizabeth; Estrada-Martinez, Sergio; Perez-Alamos, Alma Rosa; Ortiz-Jurado, Maria Nalleli; Molotla-de-Leon, Gabriel; Beristain Garcia, Isabel; Rabago-Sanchez, Elizabeth; Liesenfeld, Oliver

2016-01-01

Background The parasite Toxoplasma gondii (T. gondii) may invade the brain and might induce behavioral changes. We sought to determine the association of T. gondii infection and mixed anxiety and depressive disorder. Methods Through an age- and gender-matched case-control seroprevalence study, we examined 65 patients suffering from mixed anxiety and depressive disorder (WHO ICD-10 code: F41.2) attending in a public hospital of mental health and 260 control subjects without this disorder from the general population. Sera of participants were analyzed for anti-Toxoplasma IgG and IgM antibodies using enzyme-linked immunoassays. Results Fifteen (23.1%) of the 65 patients and 18 (6.9%) of the 260 controls had anti-T. gondii IgG antibodies (odds ratio (OR): 4.03; 95% confidence interval (CI): 1.90 - 8.53; P < 0.001). The frequency of high (> 150 IU/mL) anti-T. gondii IgG levels was similar in cases and controls (OR: 0.25; 95% CI: 0.05 - 1.06; P = 0.05). Seroprevalence was similar in male cases and controls (P = 1.0); however, seroprevalence was significantly higher in female cases than in female controls (OR: 7.08; 95% CI: 2.83 - 17.67; P < 0.00001). Patients aged 31 - 50 years old had a significantly higher seroprevalence of T. gondii infection than controls of the same age group (OR: 21.04; 95% CI: 5.22 - 84.80; P < 0.00001). Anti-T. gondii IgM antibodies were found in four (26.7%) of the 15 anti-T. gondii IgG seropositive cases and in 10 (55.6%) of the 18 anti-T. gondii IgG seropositive controls (P = 0.15). Conclusions Results support for the first time an association between seropositivity to T. gondii and mixed anxiety and depressive disorder. Further research to confirm this association and to determine the seroepidemiology of T. gondii infection in patients with this disorder is needed. PMID:27298660

Toxoplasma gondii Infection and Mixed Anxiety and Depressive Disorder: A Case-Control Seroprevalence Study in Durango, Mexico.

PubMed

Alvarado-Esquivel, Cosme; Sanchez-Anguiano, Luis Francisco; Hernandez-Tinoco, Jesus; Berumen-Segovia, Luis Omar; Torres-Prieto, Yazmin Elizabeth; Estrada-Martinez, Sergio; Perez-Alamos, Alma Rosa; Ortiz-Jurado, Maria Nalleli; Molotla-de-Leon, Gabriel; Beristain Garcia, Isabel; Rabago-Sanchez, Elizabeth; Liesenfeld, Oliver

2016-07-01

The parasite Toxoplasma gondii (T. gondii) may invade the brain and might induce behavioral changes. We sought to determine the association of T. gondii infection and mixed anxiety and depressive disorder. Through an age- and gender-matched case-control seroprevalence study, we examined 65 patients suffering from mixed anxiety and depressive disorder (WHO ICD-10 code: F41.2) attending in a public hospital of mental health and 260 control subjects without this disorder from the general population. Sera of participants were analyzed for anti-Toxoplasma IgG and IgM antibodies using enzyme-linked immunoassays. Fifteen (23.1%) of the 65 patients and 18 (6.9%) of the 260 controls had anti-T. gondii IgG antibodies (odds ratio (OR): 4.03; 95% confidence interval (CI): 1.90 - 8.53; P < 0.001). The frequency of high (> 150 IU/mL) anti-T. gondii IgG levels was similar in cases and controls (OR: 0.25; 95% CI: 0.05 - 1.06; P = 0.05). Seroprevalence was similar in male cases and controls (P = 1.0); however, seroprevalence was significantly higher in female cases than in female controls (OR: 7.08; 95% CI: 2.83 - 17.67; P < 0.00001). Patients aged 31 - 50 years old had a significantly higher seroprevalence of T. gondii infection than controls of the same age group (OR: 21.04; 95% CI: 5.22 - 84.80; P < 0.00001). Anti-T. gondii IgM antibodies were found in four (26.7%) of the 15 anti-T. gondii IgG seropositive cases and in 10 (55.6%) of the 18 anti-T. gondii IgG seropositive controls (P = 0.15). Results support for the first time an association between seropositivity to T. gondii and mixed anxiety and depressive disorder. Further research to confirm this association and to determine the seroepidemiology of T. gondii infection in patients with this disorder is needed.

Antibody responses to tetanus toxoid and Haemophilus influenzae type b conjugate vaccines following autologous peripheral blood stem cell transplantation (PBSCT).

PubMed

Chan, C Y; Molrine, D C; Antin, J H; Wheeler, C; Guinan, E C; Weinstein, H J; Phillips, N R; McGarigle, C; Harvey, S; Schnipper, C; Ambrosino, D M

1997-07-01

Accelerated granulocyte and platelet recovery following peripheral blood stem cell transplantation (PBSCT) are well documented. We hypothesize that functional immunity may also be enhanced in PBSCT and performed a phase II trial of immunizations in patients with lymphoma undergoing autologous transplantation with peripheral blood stem cells or bone marrow. Seventeen BMT and 10 PBSCT recipients were immunized at 3, 6, 12, and 24-months post-transplantation with Haemophilus influenzae type b (HIB)-conjugate and tetanus toxoid (TT) vaccines. IgG anti-HIB and anti-TT antibody concentrations were measured and compared between the two groups. Geometric mean IgG anti-HIB antibody concentrations were significantly higher for PBSCT recipients compared to BMT recipients at 24 months post-transplantation (11.3 micrograms/ml vs 0.93 microgram/ml, P = 0.051) and following the 24 month immunization (66.2 micrograms/ml vs 1.30 micrograms/ml, P = 0.006). Similar results were noted for IgG anti-TT antibody with significantly higher geometric mean antibody concentrations in the PBSCT group at 24 months post-transplantation (182 micrograms/ml vs 21.6 micrograms/ml, P = 0.039). Protective levels of total anti-HIB antibody were achieved earlier in PBSCT recipients compared with those of BMT recipients. PBSCT recipients had higher antigen-specific antibody concentrations following HIB and TT immunizations. These results suggest enhanced recovery of humoral immunity in PBSCT recipients and earlier protection against HIB with immunization.

Toxoplasma gondii antibody profile in HIV-1-infected and uninfected pregnant women and the impact on congenital toxoplasmosis diagnosis in Rio de Janeiro, Brazil.

PubMed

Fernandes, Márcia Antunes; Batista, Giovanni Inácio; Carlos, Juliano da Costa Silveira; Gomes, Ivete Martins; Azevedo, Kátia Martins Lopes de; Setúbal, Sérgio; Oliveira, Solange Artimos de; Velarde, Luis Guilhermo Coca; Cardoso, Claudete Aparecida Araújo

2012-01-01

Compare the anti-T. gondii IgG titer between HIV-1 infected and non HIV-1 infected pregnant women and report three cases of congenital toxoplasmosis resulting from reactivation of infection during pregnancy of HIV-1 infected women. This study was conducted among 2,270 pregnant women with chronic Toxoplasma gondii infection (absence of IgM and presence of IgG), including 82 HIV-1 infected and 2,188 non-infected women. The average anti-T. gondii IgG titer was 127 for the 2,188 non-HIV-1 infected women, and 227 for the 82 HIV-1-infected women (p = 0,007). These results suggested that higher anti-T. gondii IgG titers in HIV-1-infected pregnant women may not be indicative of an elevated risk for fetal infection. In this study three cases of congenital toxoplasmosis that resulted from infection reactivation during pregnancy of HIV-1-infected women were manifested by fetal death, symptomatic infection, and infant without symptoms, respectively. In two of these women, a ten-fold increase in IgG levels above used cutoff was observed (2,320 UI/mL and 3,613 UI/mL, respectively). In the third pregnant women anti-T. gondii IgG titers during pregnancy did not rise despite the occurrence of congenital toxoplasmosis (204; 198; 172 UI/mL). Congenital toxoplasmosis resulting reactivation of infection during pregnancy in the studied group leads us to believe that it is a public health problem, especially in our population, in which seroprevalence of T. gondii infections is high. These findings also suggest that special attention is necessary during pregnancy, because the serologic diagnosis may not be indicative of toxoplasmosis reactivation.

IgG4 related sclerosing mastitis: expanding the morphological spectrum of IgG4 related diseases.

PubMed

Chougule, Abhijit; Bal, Amanjit; Das, Ashim; Singh, Gurpreet

2015-01-01

IgG4 related disease (IgG4RD) is a recently recognised condition characterised by mass forming lesions associated with storiform fibrosis, obliterative phlebitis, lymphoplasmacytic infiltrate rich in IgG4 positive plasma cells and elevated serum IgG4 levels. Although rare, mammary involvement has been reported as IgG4 related sclerosing mastitis, the morphological counterpart of a growing family of IgG4 related diseases. A total of 17 cases belonging to mass forming benign inflammatory breast lesions such as plasma cell mastitis, granulomatous lobular mastitis, non-specific mastitis and inflammatory pseudotumour were investigated as a possible member of IgG4 related sclerosing mastitis. Clinical, radiological, histopathological and immunohistochemistry findings were noted in all cases. Cases diagnosed as inflammatory pseudotumour showed all the histopathological features of IgG4RD along with increased number of IgG4 positive plasma cells and IgG4/IgG ratio >40%. However, only a few IgG4 positive cells were seen in plasma cell mastitis, granulomatous lobular mastitis and non-specific mastitis cases. These cases also did not fulfill the morphological criteria for the diagnosis of IgG4 related diseases. IgG4RD should be excluded in plasma cell rich lesions diagnosed on core biopsies by IgG4 immunostaining. This can avoid unnecessary surgery as IgG4 related diseases respond to simple and effective steroid treatment.

Immunoglubolin dynamics and cancer prevalence in Tasmanian devils (Sarcophilus harrisii)

PubMed Central

Ujvari, Beata; Hamede, Rodrigo; Peck, Sarah; Pemberton, David; Jones, Menna; Belov, Katherine; Madsen, Thomas

2016-01-01

Immunoglobulins such as IgG and IgM have been shown to induce anti-tumour cytotoxic activity. In the present study we therefore explore total serum IgG and IgM expression dynamics in 23 known-aged Tasmanian devils (Sarcophilus harrisii) of which 9 where affected by Devil Facial Tumour Disease (DFTD). DFTD is clonally transmissible cancer that has caused massive declines in devil numbers. Our analyses revealed that IgM and IgG expression levels as well as IgM/IgG ratios decreased with increasing devil age. Neither age, sex, IgM nor IgG expression levels affected devil DFTD status in our analyses. However, devils with increased IgM relative to IgG expression levels had significantly lower DFTD prevalence. Our results therefore suggest that IgM/IgG ratios may play an important role in determining devil susceptibility to DFTD. We consequently propose that our findings warrant further studies to elucidate the underpinning(s) of devil IgM/IgG ratios and DFTD status. PMID:27126067

Low pretransplant IgA level is associated with early post-lung transplant seromucous infection.

PubMed

Murthy, Sudish C; Avery, Robin K; Budev, Marie; Gupta, Sandeep; Pettersson, Gösta B; Nowicki, Edward R; Mehta, Atul; Chapman, Jeffrey T; Rajeswaran, Jeevanantham; Blackstone, Eugene H

2018-04-13

Infection is an important cause of morbidity and mortality after lung transplantation. Immunoglobulins are part of both seromucous (IgA) and serum (IgG) infection defense mechanisms. We therefore hypothesized that lower pretransplant IgA levels would be associated with more early post-lung transplant seromucous infections and greater mortality independent of IgG. From January 2000 to July 2010, 538 patients undergoing primary lung transplantation had pretransplant IgA (n = 429) and IgG (n = 488) measured as a clinical routine. Median IgA was 200 mg·dL -1 (2% < 70 mg·dL -1 , lower limit of normal); median IgG was 970 mg·dL -1 (5% < 600 mg·dL -1 ). Intensive microbiology review was used to categorize infections and their causative organisms within the first posttransplant year. In total, 397 seromucous infections were observed in 247 patients, most bacterial. Although IgA and IgG were moderately correlated (r = 0.5, P < .0001), low pretransplant IgA was a strong risk factor (P = .01) for seromucous infections, but pretransplant IgG was not (P ≥ .6). As pretransplant IgA levels fell below 200 mg·dL -1 , the risk of these posttransplant infections rose nearly linearly. Lower pretransplant levels of IgA were associated with greater posttransplant mortality to end of follow-up (P = .004), but pretransplant IgG was not (P ≥ .3). Low levels of preoperative IgA, an important immunoglobulin involved in mucosal immunologic defense, but not IgG, are associated with seromucous infections in the year after lung transplantation and increased follow-up mortality. It would appear prudent to identify patients with relative IgA deficiency at listing and to increase vigilance of monitoring for, and prophylaxis against, seromucous infection in this high-risk population. Copyright © 2018. Published by Elsevier Inc.

IgG4-Related Kidney Disease: Report of a Case Presenting as a Renal Mass.

PubMed

Bianchi, Daniele; Topazio, Luca; Gaziev, Gabriele; Iacovelli, Valerio; Bove, Pierluigi; Mauriello, Alessandro; Finazzi Agrò, Enrico

2017-01-01

IgG4-related disease (IgG4-RD) is a nosological entity defined as a chronic immune-mediated fibro-inflammatory condition characterized by a tendency to form tumefactive, tissue-destructive lesions or by organ failure. Urologic involvement in IgG4-RD has been described in some short series of patients and in isolated case reports, most often involving the kidneys in so-called IgG4-related kidney disease (IgG4-RKD). The disease can occasionally mimic malignancies and is at risk of being misdiagnosed due to its rarity. We report the case of a 56-year-old man presenting with a right renal mass suspected of being malignant. Laboratory tests showed normal creatinine levels, a high erythrocyte sedimentation rate, and high levels of C-reactive protein and microalbuminuria. The patient underwent radical right nephroureterectomy and histopathologic examination revealed features proving IgG4-RKD. He was therefore referred to immunologists. Typical clinical presentation of IgG4-RKD includes altered renal function with inconstant or no radiologic findings. Conversely, in the case we presented, a single nodule was detected upon imaging evaluation, thus mimicking malignancy. This raises the issue of a proper differential diagnosis. A multidisciplinary approach can be useful, although in clinical practice the selection of patients suspected of having IgG4-RKD is critical in the cases presenting with a renal mass that mimics malignancy.

Relative stabilities of IgG1 and IgG4 Fab domains: Influence of the light–heavy interchain disulfide bond architecture

PubMed Central

Heads, James T; Adams, Ralph; D'Hooghe, Lena E; Page, Matt J T; Humphreys, David P; Popplewell, Andrew G; Lawson, Alastair D; Henry, Alistair J

2012-01-01

The stability of therapeutic antibodies is a prime pharmaceutical concern. In this work we examined thermal stability differences between human IgG1 and IgG4 Fab domains containing the same variable regions using the thermofluor assay. It was found that the IgG1 Fab domain is up to 11°C more stable than the IgG4 Fab domain containing the same variable region. We investigated the cause of this difference with the aim of developing a molecule with the enhanced stability of the IgG1 Fab and the biological properties of an IgG4 Fc. We found that replacing the seven residues, which differ between IgG1 CH1 and IgG4 CH1 domains, while retaining the native IgG1 light-heavy interchain disulfide (L–H) bond, did not affect thermal stability. Introducing the IgG1 type L–H interchain disulfide bond (DSB) into the IgG4 Fab resulted in an increase in thermal stability to levels observed in the IgG1 Fab with the same variable region. Conversely, replacement of the IgG1 L–H interchain DSB with the IgG4 type L–H interchain DSB reduced the thermal stability. We utilized the increased stability of the IgG1 Fab and designed a hybrid antibody with an IgG1 CH1 linked to an IgG4 Fc via an IgG1 hinge. This construct has the expected biophysical properties of both the IgG4 Fc and IgG1 Fab domains and may therefore be a pharmaceutically relevant format. PMID:22761163

Seroprevalence, Seroconversion, and Risk Factors for Toxoplasmosis among Pregnant Women in Taipei, Taiwan.

PubMed

Hung, Ching-Sheng; Su, Hung-Wen; Lee, Yu-Luen; Weng, Hui-Wen; Wang, Yin-Chin; Naito, Toshio; Tsubouchi, Akiko; Wang, Giueng-Chueng; Fan, Chia-Kwung

2015-01-01

Herein, we determined the seroprevalence, seroconversion, and risk factors associated with Toxoplasma gondii (T. gondii) infection among pregnant women in Taipei, Taiwan. Pregnant women attending antenatal consultation in a Taipei medical center were invited, and 104 women completed a self-administered structured questionnaire. Venous blood samples were collected during the first and third trimester after consent was obtained. Serum IgG and IgM antibodies (Abs) as well as IgG avidity were analyzed using an enzyme-linked fluorescent assay. Of the samples collected in the first trimester, seven were seropositive for IgG Abs and one was seropositive for IgG + IgM Abs with a borderline avidity index, resulting in an overall seroprevalence of 7.7%. No statistically significant association was found between toxoplasmosis and age, pregnancy history, or any risk factors. Seroconversion was not detected from paired sera between the first and third trimesters. Pregnant women with senior high school education level or those who claimed to knowing Toxoplasma exhibited a significantly higher seroprevalence than those with bachelor degree (P = 0.05) or those who claimed not to have this knowledge (P = 0.05). Therefore, failure to understand the importance of T. gondii infection and the prevention measures resulted in the development of toxoplasmosis among these women.

Immunoprotection of recombinant Eg.P29 against Echinococcus granulosus in sheep.

PubMed

Wang, Hao; Li, Zihua; Gao, Fu; Zhao, Jiaqing; Zhu, Mingxing; He, Xin; Niu, Nan; Zhao, Wei

2016-06-01

This study aims to investigate the immunoprotection of recombinant Eg.P29 (rEg.P29) vaccine and analyze the underlying mechanism in sheep. Three groups of male sheep were immunized subcutaneously with rEg.P29 and PBS, Freund's complete adjuvant as controls, respectively. After prime-boost vaccination, the sheep were challenged with encapsulated Echinococcus granulosus eggs. The percentage of protection in sheep was determined 36 weeks after the infection. Humoral immune response was analyzed for specific IgG, IgG1, IgG2, IgM and IgE levels. Moreover, cytokines including interferon (IFN)-γ, interleukin (IL)-2, IL-4,and IL-10 were also evaluated. Immunization with rEg.P29 induced protective immune responses up to 94.5 %, compared with immunoadjuvant group. The levels of specific IgG, IgG1, IgG2, and IgE as well as IFN-γ, IL-2, and IL-4 significantly increased after two immunizations (P < 0.05); however, the levels of IgM and IL-10 did not show difference. rEg.P29 showed Immunoprotection and induced Th1 and Th2 immune responses; hence, rEg.P29 is a potential vaccine for E. granulosus infection.

Sequential determination of serum viral titers, virus-specific IgG antibodies, and TNF-α, IL-6, IL-10, and IFN-γ levels in patients with Crimean-Congo hemorrhagic fever.

PubMed

Kaya, Safak; Elaldi, Nazif; Kubar, Ayhan; Gursoy, Nevcihan; Yilmaz, Meral; Karakus, Gulderen; Gunes, Turabi; Polat, Zubeyde; Gozel, Mustafa Gokhan; Engin, Aynur; Dokmetas, Ilyas; Bakir, Mehmet; Yilmaz, Neziha; Sencan, Mehmet

2014-07-28

Although there have been a number of studies on the pathogenesis of Crimean-Congo hemorrhagic fever (CCHF) recently, knowledge on this topic is still insufficient. This study aims to reveal the kinetics of serum CCHF virus (CCHFV) titers, serum levels of anti-CCHFV immunoglobulin (Ig)G, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, and interferon (IFN)-γ in CCHF patients. In total, 31 CCHF cases (11 fatal) were studied. Serum samples were obtained daily from all patients from the time of admission and continued for a 7-day hospitalization period for serologic (ELISA), virologic (real-time PCR), and cytokine (ELISA) analysis. The mean serum CCHFV titer at admission was 5.5E + 09 copies/mL in fatal cases and 5.7E + 08 copies/mL in survivors (p < 0.001). Compared to survivors, both the mean serum levels of IL-6 and TNF-α at admission were found to be significantly increased in fatal cases. The serum levels of IL-6, TNF-α and serum CCHFV titer at admission were significantly and positively correlated with disseminated intravascular coagulation (DIC) scores (r = 0.626, p = 0.0002; r = 0.461, p = 0.009; and r = 0.625, p = 0.003, respectively). When the data obtained from the sequential determination of CCHFV titer and levels of anti-CCHFV IgG, IL-6, TNF-α, IL-10 and IFN-γ were grouped according to the days of illness, the initial serum CCHFV titer of a fatal patient was 5.5E + 09 (copies/mL) and it was 6.1E + 09 (copies/mL) in a survivor on the 2 day of illness. While significant alterations were observed in all cytokines during the monitoring period, IL-6 levels remained consistently higher in fatal cases and TNF-α levels increased in both in fatal and non-fatal CCHF cases. The increased CCHFV load and higher concentrations of IL-6 and TNF-α, the presence of DIC, and the absence of CCHFV specific immunity are strongly associated with death in CCHF.

Giardiasis in mice: analysis of humoral and cellular immune responses to Giardia muris.

PubMed

Anders, R F; Roberts-Thomson, I C; Mitchell, G F

1982-01-01

Humoral and cellular immune responses have been evaluated in two inbred strains of mice which differ markedly in their susceptibility to infection with Giardia muris. Serum IgG and IgA antibody levels and IgA levels in intestinal washes were determined by a solid-phase radioimmunoassay using G. muris antigen prepared by sonication of trophozoites, while cell-mediated immunity was assessed by a radiometric ear-assay for delayed-type hypersensitivity. Following infection of BALB/c mice (resistant) and C3H/He mice (susceptible), the IgG and IgA antibody levels in serum progressively increased over the period of study with C3H/He mice having significantly higher titres of IgA antibodies than BALB/c late in the infection. Systemic immunization with G. muris trophozoites resulted in high titres of IgG antibodies in the serum. IgA antibodies were detected in intestinal washes 2 weeks after infection with a subsequent fall in levels in BALB/c mice but a progressive increase levels in C3H/He mice. Prior immunization resulted in IgA antibodies being detected earlier in the intestinal washings after a challenge infection. Delayed-type hypersensitivity to G. muris antigens could not be detected during an infection but a positive response was elicited following antigen priming in mice pretreated with cyclophosphamide. The immune responses evaluated in this study were assessed using a whole G. muris trophozoite sonicate and variations in the quantitative aspects of the responses did not account for observed differences in the course of infection in the two strains of mice.

Seroepidemiology of diphtheria and pertussis in Beijing, China: A cross-sectional study

PubMed Central

Li, Xiaomei; Chen, Meng; Zhang, Tiegang; Li, Juan; Zeng, Yang; Lu, Li

2015-01-01

The aim of this study was to assess the level of humoral immunity against diphtheria and pertussis by measuring IgG to diphtheria toxoid (DT) and pertussis toxin (PT) in general population of Beijing. A total of 2147 subjects aged 0–74 y were selected with a random sample of resident population in Beijing. The information of socio-demographic characteristics, vaccination history, disease history of diphtheria and pertussis were collected for each subject by questionnaire. Serum samples were tested for IgG antibodies to DT and PT by using commercial ELISA kits. The overall positivity rate of anti-DT IgG was 66.28% with the mean concentration of 2.169 IU/ml. Age stratified data showed that the highest positivity rate of 97.63% was observed in 1–4 y and the rates decreased with age. The positivity rates were only around 50% or below since 25 y old. The positivity rate of anti-PT IgG was 12.34% with the mean concentration of 15.163 IU/ml. The highest level of positivity rate (22.23%) and antibody level (23.101 IU/ml) was seen in <1 year old. In subjects older than 10 y old, the anti-PT IgG positivity rate was 10.19%–13.51% and concentration was 13.295 IU/ml −16.353 IU/ml, with no significant differences between these groups (χ2 = 1.664, P = 0.948; F = 0.369, P = 0.899). The subjects with anti-PT IgG ≥100 IU/ml were observed in nearly all the groups older than 5 y except for 10–14 age group. The estimated incidences of pertussis infection were higher than 6000/100000 in these age groups. A sharp increase of immunity level of diphtheria was observed at 1 y and 6 y respectively, which was consistent with the current immunization schedule. But there was no significant increase of immunity to pertussis observed after booster immunization at 18–24 months, but the proportions of undetectable were lowest in <1, 1, 2 years in children <14 years. As shown in the present study, the adult population was generally lack of protective antibody against diphtheria and all the age groups showed a low immunity to pertussis indicating the potential risk of transmission and outbreaks of the 2 diseases in Beijing. PMID:26177302

Promotion of allergic immune responses by intranasally-administrated nanosilica particles in mice

NASA Astrophysics Data System (ADS)

Yoshida, Tokuyuki; Yoshioka, Yasuo; Fujimura, Maho; Yamashita, Kohei; Higashisaka, Kazuma; Morishita, Yuki; Kayamuro, Hiroyuki; Nabeshi, Hiromi; Nagano, Kazuya; Abe, Yasuhiro; Kamada, Haruhiko; Tsunoda, Shin-Ichi; Itoh, Norio; Yoshikawa, Tomoaki; Tsutsumi, Yasuo

2011-12-01

With the increase in use of nanomaterials, there is growing concern regarding their potential health risks. However, few studies have assessed the role of the different physical characteristics of nanomaterials in allergic responses. Here, we examined whether intranasally administered silica particles of various sizes have the capacity to promote allergic immune responses in mice. We used nanosilica particles with diameters of 30 or 70 nm (nSP30 or nSP70, respectively), and conventional micro-sized silica particles with diameters of 300 or 1000 nm (nSP300 or mSP1000, respectively). Mice were intranasally exposed to ovalbumin (OVA) plus each silica particle, and the levels of OVA-specific antibodies (Abs) in the plasma were determined. Intranasal exposure to OVA plus smaller nanosilica particles tended to induce a higher level of OVA-specific immunoglobulin (Ig) E, IgG and IgG1 Abs than did exposure to OVA plus larger silica particles. Splenocytes from mice exposed to OVA plus nSP30 secreted higher levels of Th2-type cytokines than mice exposed to OVA alone. Taken together, these results indicate that nanosilica particles can induce allergen-specific Th2-type allergic immune responses in vivo. This study provides the foundations for the establishment of safe and effective forms of nanosilica particles.

Serum immunoglobulin E response as a marker for unfavorable prognosis following cholesteryl pullulan-MAGE A4 vaccination

PubMed Central

Abiko, Takehiro; Tsuchikawa, Takahiro; Miyauchi, Kengo; Wada, Masataka; Kyogoku, Noriaki; Shichinohe, Toshiaki; Miyahara, Yoshihiro; Kageyama, Shinichi; Ikeda, Hiroaki; Shiku, Hiroshi; Hirano, Satoshi

2018-01-01

Since 2009, a cancer vaccine clinical trial was conducted with melanoma antigen gene-A4 as an immunogenic agent. The levels of IgG1, IgG2 and IgG3, which are known to be Type 1 T helper cell-associated antibodies, and the levels of IgG4 and IgE, which are known to be Type 2 T helper cell-associated antibodies, were measured and used as biomarkers for predicting therapeutic effect. The results of the present study indicated a strong positive correlation between IgG2 and IgG4, with a correlation coefficient of R=0.808 (P<0.0001). The survival time of patients in which IgE responses were induced was significantly shorter compared with the survival time of patients with no IgE induction. The results of the present study suggest that caution is required when antigen-specific IgE responses are induced during cancer vaccination therapy. PMID:29467889

Circulating antibodies to Saccharomyces cerevisiae (bakers'/brewers' yeast) in gastrointestinal disease.

PubMed Central

Darroch, C J; Barnes, R M; Dawson, J

1999-01-01

AIM: To measure circulating antibodies to yeast organisms that could be used to characterise the yeast specific immune response in gastrointestinal disease. METHODS: A quantitative, isotype specific enzyme linked immunosorbent assay was developed to measure circulating antibodies to an aqueous extract of Saccharomyces cerevisiae (sacc). Comparisons of specific antibody concentrations were made between 224 healthy controls and 51 patients with Crohn's disease, 41 with ulcerative colitis, 24 with indeterminate colitis, 23 with chronic liver disease, 17 with coeliac disease, and seven with irritable bowel syndrome. Additional comparisons were made between Crohn's disease and ulcerative colitis patients. Within the Crohn's disease group, the dependence of antibody levels on several clinical variables was assessed. RESULTS: IgG and IgA anti-sacc antibodies were significantly raised in Crohn's disease. IgG antibodies were also raised in patients with chronic liver disease. Among patients with Crohn's disease, IgG antibody concentrations were higher in those with serum alpha 1 acid glycoprotein (AAG) above the normal range and there was a strong trend towards increased IgG anti-sacc in the presence of small bowel disease, whereas IgA anti-sacc correlated positively with disease duration. No differences were detected according to whether patients were taking steroids. Neither the Crohn's disease nor the chronic liver disease group differed from normal subjects in respect of IgG antibodies to bovine milk casein. On linear regression analysis of complete data from 39 Crohn's disease patients, AAG was found to be a significant predictor of both IgG and IgA antibodies, and male sex and disease duration to be additional predictors of IgA antibodies. There was a significant difference in IgG antibodies between Crohn's disease and ulcerative colitis. CONCLUSIONS: Raised antibodies to yeast, although not completely specific for Crohn's disease, may have a future role in diagnosis. The assays described here could be used to address this question in the context of a prospective study. PMID:10343612

Quantitative analysis of blood cells and inflammatory factors in wounds.

PubMed

Cerveró-Ferragut, S; López-Riquelme, N; Martín-Tomás, E; Massa-Domínguez, B; Pomares-Vicente, J; Soler-Pérez, M; Sánchez-Hernández, J F

2017-03-02

The aim of this study was to quantify blood cells and inflammatory markers, involved in the healing process, in exudates from wounds in different healing phases, to assess these markers in order to identify the inflammatory phase of the wounds. Patients who presented with postsurgical wounds, which closed by first and second intention, and those who presented with pressure ulcers (PUs), which were closed by second intention, were included in the study. We examined wounds from 37 patients and collected samples from 52 wounds in the inflammatory phase, 30 in the proliferative phase and 29 in the maturation phase. The number of neutrophils and platelets in the exudate collected from wounds in the inflammatory phase was significantly higher (p<0.001), while the number of lymphocytes, was significantly lower in exudate from wounds in the inflammatory phase (p<0.001). Wound c-reactive protein (CRP) and immunoglobulin G (IgG) levels were higher in the inflammatory group (p<0.001). We found a significantly positive correlation between CRP levels and the percentage of neutrophils and monocytes (r=0.346, p=0.004; r=0.293, p=0.015), and a significantly negative correlation between CRP levels and the percentage of lymphocytes (r=-0.503, p<0.001). A stepwise logistic regression analysis was used to identify an optimal combination of these biomarkers. The optimal biomarker combinations were neutrophils + monocytes + platelets + IgG + CRP, with an area under the curve (AUC) of 0.981 [confidence interval (CI) 95%: 0.955-1.000, p<0.001] for the diagnosis of wounds in the inflammatory phase. The optimal cutpoint yielded 96.9 % sensitivity and 94.6 % specificity. The biomarker combination predicted the inflammatory phase and was superior to individual biomarkers. Our findings suggest that the combination of the markers, percentage of neutrophils and monocytes, platelets, CRP and IgG levels could be useful prognostic indicators of the inflammatory phase.

Immunomodulatory impression of anti and pro-inflammatory cytokines in relation to humoral immunity in human scabies

PubMed Central

Abd El-Aal, Amany Ahmed; Hassan, Marwa Adel; Gawdat, Heba Ismail; Ali, Meran Ahmed; Barakat, Manal

2016-01-01

The chief manifestations of scabies are mediated through hypersensitivity-like reactions and immune responses which are so far not well understood and remain poorly characterized. The aim of this study is to investigate the role of inflammatory cytokines in relation to humoral immunity in patients with scabies. Serum levels of total IgE, specific IgG, IL-10, IL-6, INF-γ, and TNF-α were investigated in a cross-sectional study including 37 patients with manifestations suggestive of scabies and serologically positive for anti-Sarcoptes IgG, in addition to 20 healthy controls. The median value of total IgE was 209 (range, 17–1219 IU/mL), reflecting its wide range within cases. IL-10 showed significant higher levels (287 ± 139) in cases than in controls (17.4 ± 11.32). A positive correlation was reported between total IgE and severity of manifestations (r = 0.429, P <0.005). A significant positive correlation was observed between total IgE and both IgG and IL-6. On the contrary, a negative correlation was recorded between IL-6 and TNF-α which makes us suggested anti-inflammatory rather than pro-inflammatory effect of IL-6. Moreover, a negative correlation was noticed between the anti-inflammatory cytokine IL-10 and severity of manifestations, specific IgG, total IgE, and INF-γ. Therefore, the current study theorized a regulatory role of IL-10 in inflammatory responses of scabietic patients suggesting further future analysis of its therapeutic potential. PMID:26813861

Celiac disease serum markers and recurrent pregnancy loss.

PubMed

Sharshiner, Rita; Romero, Stephanie T; Bardsley, Tyler R; Branch, D Ware; Silver, Robert M

2013-12-01

Celiac disease has been associated with numerous unfavorable health outcomes, including pregnancy complications such as infertility, preterm birth, and preeclampsia. However, the association between celiac disease and recurrent pregnancy loss (RPL) remains uncertain. Our purpose was to compare serum markers of celiac disease in women with and without RPL. Therefore, we performed a case-control study of 116 women with unexplained recurrent pregnancy loss and 116 age-matched controls. Maternal sera were analyzed for immunoglobulin A (IgA) and immunoglobulin G (IgG) tissue transglutaminase (tTG) antibodies and endomysial (EM) antibodies. Groups were similar with regard to age, race and ethnicity, and BMI. One case and one control tested positive (≥20 Units) for IgA tTG antibodies and mean levels of IgA tTG antibodies were similar in cases and controls (5.5±2.86 versus 6.0±12.45; p=0.16). No cases or controls were positive for IgG tTG antibodies. However, cases had higher levels of IgG tTG antibody compared with controls (4.0±2.40 versus 3.3±1.30; p=0.0064). One subject (a control) tested positive for IgA EM antibodies and no subjects tested positive for IgG EM antibodies. In conclusion, positive results for tTG and EM antibodies were similar in women with and without RPL. Given these results, testing for occult celiac disease is not recommended in the evaluation of women with idiopathic RPL. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Mucosal immunogenicity of plant lectins in mice

PubMed Central

Lavelle, E C; Grant, G; Pusztai, A; Pfüller, U; O’Hagan, D T

2000-01-01

The mucosal immunogenicity of a number of plant lectins with different sugar specificities was investigated in mice. Following intranasal (i.n.) or oral administration, the systemic and mucosal antibody responses elicited were compared with those induced by a potent mucosal immunogen (cholera toxin; CT) and a poorly immunogenic protein (ovalbumin; OVA). After three oral or i.n. doses of CT, high levels of specific serum antibodies were measured and specific IgA was detected in the serum, saliva, vaginal wash, nasal wash and gut wash of mice. Immunization with OVA elicited low titres of serum IgG but specific IgA was not detected in mucosal secretions. Both oral and i.n. delivery of all five plant lectins investigated [Viscum album (mistletoe lectin 1; ML‐1), Lycospersicum esculentum (tomato lectin; LEA), Phaseolus vulgaris (PHA), Triticum vulgaris (wheat germ agglutinin (WGA), Ulex europaeus I (UEA‐1)] stimulated the production of specific serum IgG and IgA antibody after three i.n. or oral doses. Immunization with ML‐1 induced high titres of serum IgG and IgA in addition to specific IgA in mucosal secretions. The response to orally delivered ML‐1 was comparable to that induced by CT, although a 10‐fold higher dose was administered. Immunization with LEA also induced high titres of serum IgG, particularly after i.n. delivery. Low specific IgA titres were also detected to LEA in mucosal secretions. Responses to PHA, WGA and UEA‐1 were measured at a relatively low level in the serum, and little or no specific mucosal IgA was detected. PMID:10651938

Immunomodulatory impression of anti and pro-inflammatory cytokines in relation to humoral immunity in human scabies.

PubMed

Abd El-Aal, Amany Ahmed; Hassan, Marwa Adel; Gawdat, Heba Ismail; Ali, Meran Ahmed; Barakat, Manal

2016-06-01

The chief manifestations of scabies are mediated through hypersensitivity-like reactions and immune responses which are so far not well understood and remain poorly characterized. The aim of this study is to investigate the role of inflammatory cytokines in relation to humoral immunity in patients with scabies. Serum levels of total IgE, specific IgG, IL-10, IL-6, INF-γ, and TNF-α were investigated in a cross-sectional study including 37 patients with manifestations suggestive of scabies and serologically positive for anti-Sarcoptes IgG, in addition to 20 healthy controls. The median value of total IgE was 209 (range, 17-1219 IU/mL), reflecting its wide range within cases. IL-10 showed significant higher levels (287 ±: 139) in cases than in controls (17.4 ± 11.32). A positive correlation was reported between total IgE and severity of manifestations (r = 0.429, P <0.005). A significant positive correlation was observed between total IgE and both IgG and IL-6. On the contrary, a negative correlation was recorded between IL-6 and TNF-α which makes us suggested anti-inflammatory rather than pro-inflammatory effect of IL-6. Moreover, a negative correlation was noticed between the anti-inflammatory cytokine IL-10 and severity of manifestations, specific IgG, total IgE, and INF-γ. Therefore, the current study theorized a regulatory role of IL-10 in inflammatory responses of scabietic patients suggesting further future analysis of its therapeutic potential. © The Author(s) 2016.

PD-1(HIGH) Follicular CD4 T Helper Cell Subsets Residing in Lymph Node Germinal Centers Correlate with B Cell Maturation and IgG Production in Rhesus Macaques.

PubMed

Xu, Huanbin; Wang, Xiaolei; Lackner, Andrew A; Veazey, Ronald S

2014-01-01

CD4+ T follicular helper (TFH) cells guide development and maturation of B cells and are crucial for effective antibody responses. Here we found rhesus macaque TFH cells, defined as CXCR5+CD4 T cells, contain two major populations: PD-1(INT) and PD-1(HIGH) cells. Of these, PD-1(HIGH)CD4+ T cells highly co-express ICOS but little CCR7, and reside in lymph node germinal centers (GCs), but not in blood. These cells secrete IL-21 and express transcriptional factor Bcl-6 at higher levels than CXCR5+PD-1(INT)CD4+ T cells. In addition, the frequency of PD-1(HIGH)CD4+ T cells is low in lymph nodes of newborns, but increases with age. Levels of PD-1(HIGH)CD4+ T cells correlate with mature B cells in lymph nodes, and PD-1 blockade in PD-1(HIGH)CD4+ T and B cell co-cultures significantly inhibits IgG production. In summary, PD-1(HIGH)CD4+ T cells residing in GC represent a specific TFH subset that contributes to maturation of B cells and IgG production.

Serum immunoglobulin E and immunoglobulin G reactivity to Agaricus bisporus proteins in mushroom cultivation workers.

PubMed

Khakzad, Z; Hedayati, M T; Mahdian, S; Mayahi, S

2015-06-01

Although molds are regarded as the main fungal allergen sources, evidence indicates that spores of Basidiomycota including Agaricus bisporus ( A. bisporus ) can be also found at high concentrations in the environment and may cause as many respiratory allergies as molds. The aim of the present study was to evaluate specific immunoglobulin E (IgE) and immunoglobulin G (IgG) antibodies against A. bisporus via immunoblotting technique in individuals working at mushroom cultivation centers. In this study, 72 workers involved in the cultivation and harvest of button mushrooms were enrolled. For the analysis of serum IgE and IgG, A. bisporus grown in Sabouraud dextrose broth was harvested and ruptured by liquid nitrogen and glass beads. The obtained sample was centrifuged and the supernatant was collected as "crude extract" (CE). CE was separated via Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis (SDS-PAGE). The separated proteins were transferred to a nitrocellulose filter and the bands responsive to IgE and IgG were identified by anti-human conjugated antibodies. All participants were screened in terms of total IgE level. Among 72 workers, 18 (25%) had a total IgE level higher than 188 IU/mL. In SDS-PAGE, the CE of A. bisporus showed 23 different protein bands with a molecular weight range of 13-80 kDa. The sera of 23.6% and 55.5% of participants showed positive response, with specific IgE and IgG antibodies against A. bisporus in the blot, respectively. The bands with molecular weights of 62 and 68 kDa were the most reactive protein components of A. bisporus to specific IgE antibodies. Moreover, bands with molecular weights of 57 and 62 kDa showed the highest reactivity to IgG, respectively. Also, 62 and 68 kDa components were the most reactive bands with both specific IgG and IgE antibodies. The obtained findings revealed that A. bisporus has different allergens and antigens, which contribute to its potential as an aeroallergen in hypersensitivity-related reactions of the lungs.

Seroprevalence of rubella in Colombia: a birth-year cohort analysis

PubMed Central

Hincapie-Palacio, Doracelly; Lenis Ballesteros, Viviana; Ospina, Martha Ospina; Toro, Olga Lucía Pérez; Díaz, Francisco J

2013-01-01

OBJECTIVE To estimate the seroprevalence of rubella and associated factors. METHODS Population-based seroprevalence study in a random sample of 2,124 individuals, aged six to 64 years, representative by age, sex and area in Medellín, Colombia, 2009. Biological and socioeconomic variables were analyzed for their association with serum protection against rubella, according to birth-year cohort; those born before (1954-1990) and after (1991-2003) the introduction of universal immunization. Titer of IgG antibodies against the rubella virus was detected using a high sensitivity (AxSYM®Rubella IgG – Abbott Laboratories) and a high specificity test (VIDAS RUB IgG II®– BioMerieux Laboratories). Proportions and weighted averages derived from a complex sample, including a correction factor for differences in gender participation, were estimated. Association with protection for groups of biological and social variables according to birth cohort was analyzed using a logistic regression model. RESULTS Titers of IgG antibodies were higher in those born before (mean 110 UI/ml, 95%CI 100.5;120.2) compared to those born after (mean 64 UI/ml; 95%CI 54.4;72.8; p = 0.000) the introduction of mass immunization. The proportion of protection increased from 88.9% in those born 1990-1994, to 89.2% in those born 1995-1999 and to 92.1% in those born between 2000 and 2003, possibly due to boosters being administered from 1998 onwards. In those born before the introduction of the immunization, seroprotection was associated with previous contact with cases (OR 2.6; 95%CI 1.1;5.9), self- perceived health status (OR 2.5; 95%CI 1.05;6.0), educational level (OR 0.2; 95%CI 0.08;0.8) and years of residence in the neighborhood (RD 0,96; 95%CI 0.98;1.0) after adjusting for all variables. In those born after, serum protection was associated with effective sleep time (OR 1,4; 95%CI 1.09;1.8) and self-perceived health status (OR 5.5; 95%CI 1.2;23.8). CONCLUSIONS The seroprevalence profile changed with the mass immunization plan, with higher titers of IgG antibodies in those born before the start of the immunization. It is recommended that the level of long-term protection be monitored and concerted action taken to improve potentially associated socioeconomic conditions. PMID:24626546

Estimation of protective levels of anti-O-specific lipopolysaccharide immunoglobulin G antibody against experimental Escherichia coli infection.

PubMed

Schiff, D E; Wass, C A; Cryz, S J; Cross, A S; Kim, K S

1993-03-01

Serum obtained after immunization with an O18 polysaccharide-toxin A conjugate vaccine was evaluated for the estimation of protective levels of anti-O-specific lipopolysaccharide (LPS) immunoglobulin G (IgG) antibody against bacteremia and death caused by a homologous serotype of Escherichia coli K1 strains. Passive transfer of rabbit serum conferred significant protection from a lethal E. coli infection in a neonatal rat model. The overall incidence of bacteremia and mortality was 4% in rat pups receiving undiluted postvaccination serum, while that in control animals was 100% (P < 0.001). The overall incidences of bacteremia were 5 and 72% for animals with serum anti-O18 LPS IgG concentrations of > 1.0 and < 1.0 microgram/ml, respectively, while the overall incidences of mortality for animals with serum anti-O18 LPS IgG levels of > 1.0 and < 1.0 microgram/ml were 0 and 72%, respectively (P < 0.001). Protection against E. coli infection was also demonstrated with human anti-O18 polysaccharide IgG. None of the animals with human anti-O18 LPS IgG levels of > 1 microgram/ml had bacteremia after bacterial challenge, whereas all animals with bacteremia at 18 h had levels of < 1 microgram/ml. These findings suggest that serum anti-O18 LPS IgG concentrations of > 1.0 microgram/ml may provide protection against bacteremia and death caused by a homologous E. coli K1 infection.

Domestic cat microsphere immunoassays: detection of antibodies during feline immunodeficiency virus infection.

PubMed

Wood, Britta A; Carver, Scott; Troyer, Ryan M; Elder, John H; VandeWoude, Sue

2013-10-31

Microsphere immunoassays (MIAs) allow rapid and accurate evaluation of multiple analytes simultaneously within a biological sample. Here we describe the development and validation of domestic cat-specific MIAs for a) the quantification of total IgG and IgA levels in plasma, and b) the detection of IgG and IgA antibodies to feline immunodeficiency virus (FIV) capsid (CA) and surface (SU) proteins, and feline CD134 in plasma. These assays were used to examine the temporal antibody response of domestic cats infected with apathogenic and pathogenic FIVs, and domestic cats infected with parental and chimeric FIVs of varying pathogenicity. The results from these studies demonstrated that a) total IgG antibodies increase over time after infection; b) α-CA and α-SU IgG antibodies are detectable between 9 and 28 days post-infection and increase over time, and these antibodies combined represent a fraction (1.8 to 21.8%) of the total IgG increase due to infection; c) measurable α-CD134 IgG antibody levels vary among individuals and over time, and are not strongly correlated with viral load; d) circulating IgA antibodies, in general, do not increase during the early stage of infection; and e) total IgG, and α-CA and α-SU IgG antibody kinetics and levels vary with FIV viral strain/pathogenicity. The MIAs described here could be used to screen domestic cats for FIV infection, and to evaluate the FIV-specific or total antibody response elicited by various FIV strains/other diseases. © 2013.

Domestic cat microsphere immunoassays: Detection of antibodies during feline immunodeficiency virus infection

PubMed Central

Wood, Britta A.; Carver, Scott; Troyer, Ryan M.; Elder, John H.; VandeWoude, Sue

2013-01-01

Microsphere immunoassays (MIAs) allow rapid and accurate evaluation of multiple analytes simultaneously within a biological sample. Here we describe the development and validation of domestic cat-specific MIAs for a) the quantification of total IgG and IgA levels in plasma, and b) the detection of IgG and IgA antibodies to feline immunodeficiency virus (FIV) capsid (CA) and surface (SU) proteins, and feline CD134 in plasma. These assays were used to examine the temporal antibody response of domestic cats infected with apathogenic and pathogenic FIVs, and domestic cats infected with parental and chimeric FIVs of varying pathogenicity. The results from these studies demonstrated that a) total IgG antibodies increase over time after infection; b) α-CA and α-SU IgG antibodies are detectable between 9–28 days post-infection and increase over time, and these antibodies combined represent a fraction (1.8 to 21.8%) of the total IgG increase due to infection; c) measurable α-CD134 IgG antibody levels vary among individuals and over time, and are not strongly correlated with viral load; d) circulating IgA antibodies, in general, do not increase during the early stage of infection; and e) total IgG, and α-CA and α-SU IgG antibody kinetics and levels vary with FIV viral strain/pathogenicity. The MIAs described here could be used to screen domestic cats for FIV infection, and to evaluate the FIV-specific or total antibody response elicited by various FIV strains/other diseases. PMID:23954271

Anti-rubella, Mumps and Measles IgG Antibodies in Medical Students of Tehran University.

PubMed

Keshavarz, Maryam; Nicknam, Mohammad Hossein; Tebyanian, Majid; Shahkarami, Mohammad Kazem; Izad, Maryam

2016-06-01

Measles, mumps and rubella are viral infectious diseases that may result in serious complications. Since the production of vaccines, the number of cases of these diseases has been dropped. Nevertheless, these infectious diseases are still one of the major health problems in developing countries. In this study, in order to evaluate the protective responses against measles, mumps and rubella, the level and avidity of virus-specific IgG antibodies were measured in 53 medical students of Tehran University, aged between 20-30 years. Except for mumps vaccine, all the students had been vaccinated against measles and rubella according to Iran's nationwide mass vaccination protocol for all persons aged 5-25 in 2003. Our results showed that 96.2% of the volunteers had a protective level (>15 IU/ml) of IgG against rubella, 79.2% had a protective level (>11 IU/ml) of IgG against measles and 64.16% had a protective level (>11 IU/ml) of IgG against mumps. Over ten years after nationwide measles-rubella vaccination campaign, most young adults aged 20-30 had protective levels of humoral immunity against measles and rubella. However, Iranian young population is still unvaccinated against mumps, and therefore relatively large number of young adults had no protective level of IgG against it. This finding may be due to reduction in circulating of wild strain. We recommend screening of medical students for immunity against infectious agents such as measles, mumps, rubella, because they are at a high risk of these infectious agents.

Investigation of the prevalence of antibody immunodeficiency in a polio endemic area in India.

PubMed

Mohanty, Madhu C; Deshpande, Jagadish M

2014-05-01

Protection against paralytic poliomyelitis is provided mainly by antibody mediated host defense. Despite intensive oral polio vaccine (OPV) immunization campaigns wild poliovirus transmission could not be stopped in Uttar Pradesh (UP) and Bihar states of India by the end of 2010. The objective of our study was to quantitate serum IgG and IgA in children of western UP, India, to determine the prevalence of antibody immunodeficiency. A cross-sectional survey for IgG and IgA concentrations in serum samples from healthy children and children with acute flaccid paralysis (AFP), up to the age of 5 years, was performed using sandwich ELISA. The overall mean IgG concentration for 1882 children of western UP, India, was 10.57 ± 4.53 (SD) g/L and mean IgA concentration for 979 children was 1.2 ± 0.818 g/L. Two 7-month-old female children had IgG levels below 2 g/L and there was an absence of neutralizing polio antibodies. The mean serum IgG level of children with AFP (n=979) was lower than levels observed in healthy children (n=903). The proportion of children with IgG levels below 2 g/L and IgA levels below 0.07 g/L was 0.7% in both healthy children and AFP cases. There was no abnormal prevalence of immunodeficiency in children in western UP which could have delayed achieving the eradication of polio in the state. The immunoglobulin levels reported here may be used as age-specific normal values for Indian children.

Effect of transmission intensity and age on subclass antibody responses to Plasmodium falciparum pre-erythrocytic and blood-stage antigens.

PubMed

Noland, Gregory S; Jansen, Paul; Vulule, John M; Park, Gregory S; Ondigo, Bartholomew N; Kazura, James W; Moormann, Ann M; John, Chandy C

2015-02-01

Cytophilic immunoglobulin (IgG) subclass responses (IgG1 and IgG3) to Plasmodium falciparum antigens have been associated with protection from malaria, yet the relative importance of transmission intensity and age in generation of subclass responses to pre-erythrocytic and blood-stage antigens have not been clearly defined. We analyzed IgG subclass responses to the pre-erythrocytic antigens CSP, LSA-1, and TRAP and the blood-stage antigens AMA-1, EBA-175, and MSP-1 in asymptomatic residents age 2 years or older in stable (n=116) and unstable (n=96) transmission areas in Western Kenya. In the area of stable malaria transmission, a high prevalence of cytophilic (IgG1 and IgG3) antibodies to each antigen was seen in all age groups. Prevalence and levels of cytophilic antibodies to pre-erythrocytic and blood-stage P. falciparum antigens increased with age in the unstable transmission area, yet IgG1 and IgG3 responses to most antigens for all ages in the unstable transmission area were less prevalent and lower in magnitude than even the youngest age group from the stable transmission area. The dominance of cytophilic responses over non-cytophilic (IgG2 and IgG4) was more pronounced in the stable transmission area, and the ratio of IgG3 over IgG1 generally increased with age. In the unstable transmission area, the ratio of cytophilic to non-cytophilic antibodies did not increase with age, and tended to be IgG3-biased for pre-erythrocytic antigens yet IgG1-biased for blood-stage antigens. The differences between areas could not be attributed to active parasitemia status, as there were minimal differences in antibody responses between those positive and negative for Plasmodium infection by microscopy in the stable transmission area. Individuals in areas of unstable transmission have low cytophilic to non-cytophilic IgG subclass ratios and low IgG3:IgG1 ratios to P. falciparum antigens. These imbalances could contribute to the persistent risk of clinical malaria in these areas and serve as population-level, age-specific biomarkers of transmission. Copyright © 2014 Elsevier B.V. All rights reserved.

Immunization of Mice by BCG Formulated HCV Core Protein Elicited Higher Th1-Oriented Responses Compared to Pluronic-F127 Copolymer

PubMed Central

Yazdanian, Maryam; Memarnejadian, Arash; Mahdavi, Mehdi; Sadat, Seyed Mehdi; Motevali, Fatemeh; Vahabpour, Rouhollah; Khanahmad, Hossein; Siadat, Seyed Davar; Aghasadeghi, Mohammad Reza; Roohvand, Farzin

2013-01-01

Background A supreme vaccine for Hepatitis C virus (HCV) infection should elicit strong Th1-oriented cellular responses. In the absence of a Th1-specific adjuvant, immunizations by protein antigens generally induce Th2-type and weak cellular responses. Objectives To evaluate the adjuvant effect of BCG in comparison with nonionic copolymer-Pluronic F127 (F127) as a classic adjuvant in the formulation of HCV core protein (HCVcp) as a candidate vaccine for induction of Th1 immune responses. Materials and Methods Expression of N-terminally His-Tagged HCVcp (1-122) by pIVEX2.4a-core vector harboring the corresponding gene under the control of arabinose-inducible (araBAD) promoter was achieved in BL21-AI strain of E.coli and purified through application of nitrilotriacetic acid (Ni-NTA) chromatography. Mice were immunized subcutaneously (s.c.) in base of the tail with 100 μl of immunogen (F127+HCVcp or BCG+HCVcp; 5 μgHCVcp/mouse/dose) or control formulations (PBS, BCG, F127) at weeks 0, 3, 6. Total and subtypes of IgG, as well as cellular immune responses (Proliferation, In vivo CTL and IFN-γ/IL-4 ELISpot assays against a strong and dominant H2-d restricted, CD8+-epitopic peptide, core 39-48; RRGPRLGVRA of HCVcp) were compared in each group of immunized animals. Results Expression and purification of core protein around the expected size (21 kDa) was confirmed by Western blotting. The HCVcp + BCG vaccinated mice showed significantly higher lymphocyte proliferation and IFN-γ production but lower levels of cell lysis (45% versus 62% in CTL assay) than the HCVcp+F127 immunized animals. “Besides, total anti-core IgG and IgG1 levels were significantly higher in HCVcp + F127 immunized mice as compared to HCVcp + BCG vaccinated animals, indicating relatively higher efficacy of F127 for the stimulation of humoral and Th2-oriented immune responses”. Conclusions Results showed that HCVcp + BCG induced a moderate CTL and mixed Th1/Th2 immune responses with higher levels of cell proliferation and IFN-γ secretion, indicating that BCG may have a better outcome when formulated in HCVcp-based subunit vaccines. PMID:24348641

The level of BLyS (BAFF) correlates with the titre of autoantibodies in human Sjögren's syndrome.

PubMed

Mariette, X; Roux, S; Zhang, J; Bengoufa, D; Lavie, F; Zhou, T; Kimberly, R

2003-02-01

Increased levels of B lymphocyte stimulator (BLyS) have been detected in serum from patients with systemic lupus erythematosus and rheumatoid arthritis. To determine the level of BLyS in serum from patients with primary's Sjögren's syndrome (SS), another autoimmune disease in which B cell activation is high. Serum samples from 49 patients with primary SS according to the revised European criteria were assayed for BLyS, quantitative immunoglobulins, and autoantibody levels and compared with samples from 47 healthy control subjects. The median level of BLyS was 5.99 ng/ml (25th-75th centile range 3.20-8.93 ng/ml) in SS v 2.49 ng/ml (25th-75th centile range 1.96-2.96 ng/ml) in healthy controls (p<0.001). More importantly, among patients with SS, the presence of anti-SSA antibodies was associated with significantly higher levels of BLyS (medians 7.90 ng/ml v 3.70 ng/ml; p=0.008) as was the presence of anti-SSB antibodies (medians 7.14 ng/ml v 3.70 ng/ml; p=0.02) and of rheumatoid factor (medians 7.70 ng/ml v 3.80 ng/ml; p=0.016). The level of BLyS in three patients with a monoclonal gammopathy was higher than in the other patients (medians 26.53 ng/ml v 5.92 ng/ml; p=0.13). Higher levels of BLyS were associated with higher levels of gammaglobulins and IgG. There was a strong correlation between BLyS and rheumatoid factor level (r=0.71, p<0.0001), anti-SSA IgG level (r=0.32, p=0.02) and anti-SSA IgM level (r=0.39, p=0.006). In human SS the level of BLyS correlates with the level of autoantibodies. Thus, BLyS may play a part in activating specific autoreactive B cells and modulating the level of production of autoantibodies which are the hallmark of the disease. These findings raise the possibility of a novel therapeutic approach in human SS.

No Evidence for a Trade-Off between Reproductive Investment and Immunity in a Rodent

PubMed Central

Xu, Yan-Chao; Yang, Deng-Bao; Wang, De-Hua

2012-01-01

Life history theory assumes there are trade-offs between competing functions such as reproduction and immunity. Although well studied in birds, studies of the trade-offs between reproduction and immunity in small mammals are scarce. Here we examined whether reduced immunity is a consequence of reproductive effort in lactating Brandt's voles (Lasiopodomys brandtii). Specifically, we tested the effects of lactation on immune function (Experiment I). The results showed that food intake and resting metabolic rate (RMR) were higher in lactating voles (6≤ litter size ≤8) than that in non-reproductive voles. Contrary to our expectation, lactating voles also had higher levels of serum total Immunoglobulin G (IgG) and anti-keyhole limpet hemocyanin (KLH) IgG and no change in phytohemagglutinin (PHA) response and anti-KLH Immunoglobulin M (IgM) compared with non-reproductive voles, suggesting improved rather than reduced immune function. To further test the effect of differences in reproductive investment on immunity, we compared the responses between natural large (n≥8) and small litter size (n≤6) (Experiment II) and manipulated large (11–13) and small litter size (2–3) (Experiment III). During peak lactation, acquired immunity (PHA response, anti-KLH IgG and anti-KLH IgM) was not significantly different between voles raising large or small litters in both experiments, despite the measured difference in reproductive investment (greater litter size, litter mass, RMR and food intake in the voles raising larger litters). Total IgG was higher in voles with natural large litter size than those with natural small litter size, but decreased in the enlarged litter size group compared with control and reduced group. Our results showed that immune function is not suppressed to compensate the high energy demands during lactation in Brandt's voles and contrasting the situation in birds, is unlikely to be an important aspect mediating the trade-off between reproduction and survival. PMID:22649512

Protection of BALB/C mice against Brucella abortus 544 challenge by vaccination with combination of recombinant human serum albumin-l7/l12 (Brucella abortus ribosomal protein) and lipopolysaccharide.

PubMed

Pakzad, Iraj; Rezaee, Abbas; Rasaee, Mohammad J; Hossieni, Ahmad Zavaran; Tabbaraee, Bahman; Kazemnejad, Anoshirvan

2010-01-01

The immunogenic Brucella abortus ribosomal protein L7/L12 and Lipopolysaccharide (LPS) are promising candidate antigens for the development of subunit vaccines against brucellosis. This study was aimed to evaluate the protection of combination of recombinant HSA-L7/L12 fusion protein with LPS in Balb/c mouse. The recombinant HSA-L7/L12 fusion protein in Saccharomyces cerevisiae was expressed and purified by affinity chromatography column. LPS was extracted by n-butanol, purified by ultracentrifugation. BALB/c mouses were immunized in 9 groups with PBS, HSA, tHSA-L7/L12, L7/L12, LPS, LPS+ HSA, LPS+ tHSA-L7/L12, LPS+ L7/L12, B. abortus S19. ELISA, LTT tests and challenging two weeks after last injection were carried out. Bacterial count of spleen of immunized BALB/c mouse was done four weeks after challenging with virulent strain B. abortus 544. In ELISA test the specific antibodies of tHSA-L7/L12 exhibited a dominance of immunoglobulin IgG1 over IgG2a. LPS-HSA and tHSA-L7/L12 + LPS produced a significantly higher antibody titer than LPS alone and L7/L12+LPS (P < 0.05). The predominant IgG subtype for LPS and L7/L12+LPS were IgG3. However, tHSA-L7/L12+ LPS and LPS+ HAS elicited predominantly IgG1 and IgG3 subtypes. In addition, the tHSA-L7/L12 fusion protein and L7/L12 elicited a strong T-cell proliferative response upon restimulation in vitro with recombinant tHSA-L7/L12 and L7/L12, suggesting the induction of a cellular immunity response in vivo. However, there was no significant difference proliferative response in L7/L12 and tHSA-L7/L12 fusion protein (P > 0.05). The combination of tHSA-L7/L12 fusion protein with LPS and B. abortus S19 induce higher level of protection against challenge with the virulent strain B. abortus 544 in BALB/c mice than other groups (P = 0.005). The combination of tHSA-L7/L12 fusion protein with LPS had higher protective ability than LPS and fusion protein distinctly.

Contributions of HLA haplotypes, IL8 level and Toxoplasma gondii infection in defining celiac disease's phenotypes.

PubMed

Rostami-Nejad, Mohammad; Hejazi, Seyed Hossein; Peña, Amado Salvador; Asadzadeh-Aghdaei, Hamid; Rostami, Kamran; Volta, Umberto; Zali, Mohammad Reza

2018-05-18

It is not clear why some patients with coeliac disease (CD) present with severe symptoms and small intestinal mucosal damages while others present with milder symptoms and no frank enteropathy. There is no study to assess the associated factors with mild/severe symptoms and enteropathy. The terminologies like latent, silent and potential are difficult to use and are unrepresentative. In the present study we describe coeliac disease's phenotypes based on HLA haplotypes, IL8 production and past infection with Toxoplasma gondii (T. gondii) infection. In this case-control study, sera originating from 150 healthy subjects and 150 patients diagnosed with CD during the years 2013-14 were analyzed for the presence of antibodies specific T. gondii of the IgG and IgM subclasses. The level of IL8 were measured and HLA-DQ2 and HLA-DQ8 alleles were genotyped. The correlation between these parameters and the damages in intestinal mucosal were assessed using an accepted histopathological classification. High levels of IgG antibodies against T. gondii were found in the sera of control group compared to the CD group (52.6% vs. 39.4%, P = 0.02). Mean serum levels of IL8 was significantly higher in CD patients compared with control (P ≤ 0.05). By comparing the level of anti- T. gondii IgG and mucosal damage in celiac disease, we found a significant relationship between the severity of mucosal damages and anti- T. gondii IgG level (P = 0.02). No correlation was detected between Toxoplasma gondii infection and types of HLA (P > 0.05). However, patients with severely abnormal histology carried HLA-DQ2 risk alleles (92 patients (61%)) more often than the controls and those with mild histological abnormalities. CD patients with severe histological changes had more often Toxoplasma gondii infection than those affected with mild histological features. This suggests that CD's phenotypes are correlated to additional factors like infections and to particular HLA DQ2 alleles that may need additional investigations and potentially will require additional treatment.

Hypogammaglobulinemia associated with accelerated catabolism of IgG secondary to its interaction with an IgG-reactive monoclonal IgM

PubMed Central

Waldmann, Thomas A.; Johnson, John S.; Talal, Norman

1971-01-01

Hypogammaglobulinemia due to a new pathophysiological mechanism was studied in a patient with Sjögren's syndrome, a monoclonal IgM and a mixed (IgM-IgG) cryoglobulinemia. The IgM (IgMdk) component of the cryogel possessed light chains of λ-type with highly restricted electrophoretic mobility analagous to those of a Waldenström's macroglobulin. IgMdk reacted specifically with native IgG, with IgG subclasses 1, 2, and 4, and with the Fc piece of IgG to form a cryogel. Serum concentrations of IgG 1, 2, and 4 were 10% of normal, whereas the IgG3 level was slightly increased and the IgM level was markedly increased. Viscosity and analytical ultracentrifugation studies with the purified mixed cryogel (IgM-LgG) indicated soluble complex formation over a temperature range (36-38°C) attainable in vivo. Immunoglobulin turnover studies revealed a markedly elevated rate of IgM synthesis with a normal survival of IgM, IgA, and IgE. IgG3, which failed to form complexes with IgMdk at body temperature, had a normal synthetic rate and survival. In contrast, the other IgG subclasses showed reduced synthesis and shortened survival. These studies are the first indicating a short survival of some IgG subclasses with a normal survival of another. The hypogammaglobulinemia appears to be due in part to a new mechanism of accelerated protein catabolism: The rapid elimination of IgG due to its interaction with an IgG-reactive monoclonal IgM. PMID:4993860

Evaluation of sex, race, body mass index and pre-vaccination serum progesterone levels and post-vaccination serum anti-anthrax protective immunoglobulin G on injection site adverse events following anthrax vaccine adsorbed (AVA) in the CDC AVA human clinical trial.

PubMed

Pondo, Tracy; Rose, Charles E; Martin, Stacey W; Keitel, Wendy A; Keyserling, Harry L; Babcock, Janiine; Parker, Scott; Jacobson, Robert M; Poland, Gregory A; McNeil, Michael M

2014-06-12

Anthrax vaccine adsorbed (AVA) administered intramuscularly (IM) results in fewer adverse events (AEs) than subcutaneous (SQ) administration. Women experience more AEs than men. Antibody response, female hormones, race, and body mass index (BMI) may contribute to increased frequency of reported injection site AEs. We analyzed data from the CDC AVA human clinical trial. This double blind, randomized, placebo controlled trial enrolled 1563 participants and followed them through 8 injections (AVA or placebo) over a period of 42 months. For the trial's vaccinated cohort (n=1267), we used multivariable logistic regression to model the effects of study group (SQ or IM), sex, race, study site, BMI, age, and post-vaccination serum anti-PA IgG on occurrence of AEs of any severity grade. Also, in a women-only subset (n=227), we assessed effect of pre-vaccination serum progesterone level and menstrual phase on AEs. Participants who received SQ injections had significantly higher proportions of itching, redness, swelling, tenderness and warmth compared to the IM study group after adjusting for other risk factors. The proportions of redness, swelling, tenderness and warmth were all significantly lower in blacks vs. non-black participants. We found arm motion limitation, itching, pain, swelling and tenderness were more likely to occur in participants with the highest anti-PA IgG concentrations. In the SQ study group, redness and swelling were more common for obese participants compared to participants who were not overweight. Females had significantly higher proportions of all AEs compared to males. Menstrual phase was not associated with any AEs. Female and non-black participants had a higher proportion of AVA associated AEs and higher anti-PA IgG concentrations. Antibody responses to other vaccines may also vary by sex and race. Further studies may provide better understanding for higher proportions of AEs in women and non-black participants. Published by Elsevier Ltd.

Evaluation of sex, race, body mass index and pre-vaccination serum progesterone levels and post-vaccination serum anti-anthrax protective immunoglobulin G on injection site adverse events following anthrax vaccine adsorbed (AVA) in the CDC AVA human clinical trial✩

PubMed Central

Pondo, Tracy; Rose, Charles E.; Martin, Stacey W.; Keitel, Wendy A.; Keyserling, Harry L.; Babcock, Janiine; Parker, Scott; Jacobson, Robert M.; Poland, Gregory A.; McNeil, Michael M.

2017-01-01

Background Anthrax vaccine adsorbed (AVA) administered intramuscularly (IM) results in fewer adverse events (AEs) than subcutaneous (SQ) administration. Women experience more AEs than men. Antibody response, female hormones, race, and body mass index (BMI) may contribute to increased frequency of reported injection site AEs. Methods We analyzed data from the CDC AVA human clinical trial. This double blind, randomized, placebo controlled trial enrolled 1563 participants and followed them through 8 injections (AVA or placebo) over a period of 42 months. For the trial’s vaccinated cohort (n = 1267), we used multivariable logistic regression to model the effects of study group (SQ or IM), sex, race, study site, BMI, age, and post-vaccination serum anti-PA IgG on occurrence of AEs of any severity grade. Also, in a women-only subset (n = 227), we assessed effect of pre-vaccination serum progesterone level and menstrual phase on AEs. Results Participants who received SQ injections had significantly higher proportions of itching, redness, swelling, tenderness and warmth compared to the IM study group after adjusting for other risk factors. The proportions of redness, swelling, tenderness and warmth were all significantly lower in blacks vs. non-black participants. We found arm motion limitation, itching, pain, swelling and tenderness were more likely to occur in participants with the highest anti-PA IgG concentrations. In the SQ study group, redness and swelling were more common for obese participants compared to participants who were not overweight. Females had significantly higher proportions of all AEs compared to males. Menstrual phase was not associated with any AEs. Conclusions Female and non-black participants had a higher proportion of AVA associated AEs and higher anti-PA IgG concentrations. Antibody responses to other vaccines may also vary by sex and race. Further studies may provide better understanding for higher proportions of AEs in women and non-black participants. PMID:24768633

Increased levels of IgE and autoreactive, polyreactive IgG in wild rodents: implications for the hygiene hypothesis

USGS Publications Warehouse

Devalapalli, A.P.; Lesher, A.; Shieh, K.; Solow, J.S.; Everett, M.L.; Edala, A.S.; Whitt, P.; Long, Renee R.; Newton, N.; Parker, W.

2006-01-01

To probe the potential role of Th1 versus Th2 reactivity underlying the hygiene hypothesis, intrinsic levels of Th1-associated and Th2-associated antibodies in the serum of wild rodents were compared with that in various strains of laboratory rodents. Studies using rat lung antigens as a target indicated that wild rats have substantially greater levels of autoreactive, polyreactive immunoglobulin G (IgG), but not autoreactive, polyreactive IgM than do laboratory rats, both on a quantitative and qualitative basis. Increased levels of serum IgG and IgE were observed in both wild rats and wild mice relative to their laboratory-raised counterparts, with the effect being most pronounced for IgE levels. Further, wild rats had greater intrinsic levels of both Th1- and Th2-associated IgG subclasses than did lab rats. The habitat (wild versus laboratory raised) had a more substantial impact on immunoglobulin concentration than did age, strain or gender in the animals studied. The presence in wild rodents of increased intrinsic, presumably protective, non-pathogenic responses similar to both autoimmune (autoreactive IgG, Th1-associated) and allergic (IgE, Th2-associated) reactions as well as increased levels of Th1-associated and Th2-associated IgG subclasses points toward a generally increased stimulation of the immune system in these animals rather than a shift in the nature of the immunoreactivity. It is concluded that, at least to the extent that feedback inhibition is a controlling element of immunoreactivity, an overly hygienic environment may affect the threshold of both types of immune responses more so than the balance between the different responses.

Increased levels of IgE and autoreactive, polyreactive IgG in wild rodents: implications for the hygiene hypothesis.

PubMed

Devalapalli, A P; Lesher, A; Shieh, K; Solow, J S; Everett, M L; Edala, A S; Whitt, P; Long, R R; Newton, N; Parker, W

2006-08-01

To probe the potential role of Th1 versus Th2 reactivity underlying the hygiene hypothesis, intrinsic levels of Th1-associated and Th2-associated antibodies in the serum of wild rodents were compared with that in various strains of laboratory rodents. Studies using rat lung antigens as a target indicated that wild rats have substantially greater levels of autoreactive, polyreactive immunoglobulin G (IgG), but not autoreactive, polyreactive IgM than do laboratory rats, both on a quantitative and qualitative basis. Increased levels of serum IgG and IgE were observed in both wild rats and wild mice relative to their laboratory-raised counterparts, with the effect being most pronounced for IgE levels. Further, wild rats had greater intrinsic levels of both Th1- and Th2-associated IgG subclasses than did lab rats. The habitat (wild versus laboratory raised) had a more substantial impact on immunoglobulin concentration than did age, strain or gender in the animals studied. The presence in wild rodents of increased intrinsic, presumably protective, non-pathogenic responses similar to both autoimmune (autoreactive IgG, Th1-associated) and allergic (IgE, Th2-associated) reactions as well as increased levels of Th1-associated and Th2-associated IgG subclasses points toward a generally increased stimulation of the immune system in these animals rather than a shift in the nature of the immunoreactivity. It is concluded that, at least to the extent that feedback inhibition is a controlling element of immunoreactivity, an overly hygienic environment may affect the threshold of both types of immune responses more so than the balance between the different responses.

IgG4-Related Disease Simulating Carcinoma Colon With Diffuse Peritoneal Carcinomatosis on 18F-FDG PET/CT.

PubMed

Vadi, Shelvin Kumar; Parihar, Ashwin Singh; Kumar, Rajender; Singh, Harmandeep; Mittal, Bhagwant Rai; Bal, Amanjit; Sinha, Saroj Kumar

2018-05-14

IgG4-related disease (IgG4-RD) continues to be a diagnostic challenge and a great mimicker of malignancies. We report here a case of young man who presented with subacute intestinal obstruction with initial imaging and clinical features suggestive of carcinoma colon. 18F-FDG PET/CT showed diffuse peritoneal carcinomatosis pattern typically seen with abdominal malignancies. However, the histopathology and the raised IgG4 levels diagnosed it to be IgG4-RD. Although 18F-FDG PET/CT has typical patterns corresponding to the multisystemic involvement of IgG4-RD, the index case did not show any such findings.

Evaluation of humoral immunity profiles to identify heart recipients at risk for development of severe infections: A multicenter prospective study.

PubMed

Sarmiento, Elizabeth; Jaramillo, Maria; Calahorra, Leticia; Fernandez-Yañez, Juan; Gomez-Sanchez, Miguel; Crespo-Leiro, Maria G; Paniagua, Maria; Almenar, Luis; Cebrian, Monica; Rabago, Gregorio; Levy, Beltran; Segovia, Javier; Gomez-Bueno, Manuel; Lopez, Javier; Mirabet, Sonia; Navarro, Joaquin; Rodriguez-Molina, Juan Jose; Fernandez-Cruz, Eduardo; Carbone, Javier

2017-05-01

New biomarkers are necessary to improve detection of the risk of infection in heart transplantation. We performed a multicenter study to evaluate humoral immunity profiles that could better enable us to identify heart recipients at risk of severe infections. We prospectively analyzed 170 adult heart recipients at 8 centers in Spain. Study points were before transplantation and 7 and 30 days after transplantation. Immune parameters included IgG, IgM, IgA and complement factors C3 and C4, and titers of specific antibody to pneumococcal polysaccharide antigens (anti-PPS) and to cytomegalovirus (CMV). To evaluate potential immunologic mechanisms leading to IgG hypogammaglobulinemia, before heart transplantation we assessed serum B-cell activating factor (BAFF) levels using enzyme-linked immunoassay. The clinical follow-up period lasted 6 months. Clinical outcome was need for intravenous anti-microbials for therapy of infection. During follow-up, 53 patients (31.2%) developed at least 1 severe infection. We confirmed that IgG hypogammaglobulinemia at Day 7 (defined as IgG <600 mg/dl) is a risk factor for infection in general, bacterial infections in particular, and CMV disease. At Day 7 after transplantation, the combination of IgG <600 mg/dl + C3 <80 mg/dl was more strongly associated with the outcome (adjusted odds ratio 7.40; 95% confidence interval 1.48 to 37.03; p = 0.014). We found that quantification of anti-CMV antibody titers and lower anti-PPS antibody concentrations were independent predictors of CMV disease and bacterial infections, respectively. Higher pre-transplant BAFF levels were a risk factor of acute cellular rejection. Early immunologic monitoring of humoral immunity profiles proved useful for the identification of heart recipients who are at risk of severe infection. Copyright © 2017 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Modulation of natural IgM autoantibodies to oxidative stress-related neo-epitopes on apoptotic cells in newborns of mothers with anti-Ro autoimmunity

PubMed Central

Grönwall, Caroline; Clancy, Robert M.; Getu, Lelise; Lloyd, Katy A.; Siegel, Don L.; Reed, Joanne H.; Buyon, Jill; Silverman, Gregg J.

2016-01-01

At birth, the human immune system already contains substantial levels of polymeric IgM, with autoantibodies to neo-epitopes on apoptotic cells (ACs) that are proposed to play homeostatic and anti-inflammatory roles. Yet the biologic origins and developmental regulation of these naturally arising antibodies remain poorly understood. Herein, we report that levels of IgM-antibodies to malondialdehyde (MDA) protein adducts, a common type of in vivo generated oxidative stress-related neoepitope, directly correlate with the relative binding of neonatal-IgM to ACs. While levels of IgM to phosphorylcholine (PC), a natural antibody prevalent in adults, were relatively scant in cord blood, there was significantly greater relative representation of IgM anti-MDA antibodies in newborns compared to adults. To investigate the potential interrelationships between neonatal IgM with pathogenic IgG-autoantibodies, we studied 103 newborns born to autoimmune mothers with IgG anti-Ro (i.e., 70 with neonatal lupus and 33 without neonatal lupus). In these subjects the mean levels of IgM anti-Ro60 were significantly higher than in the newborns from non-autoimmune mothers. In contrast, levels of IgM anti-MDA in IgG anti-Ro exposed neonates were significantly lower than in neonates from non-autoimmune mothers. The presence or absence of neonatal lupus did not influence the total levels of IgM in the anti-Ro exposed newborns. Taken together, our studies provide evidence that the immune development of the natural IgM-repertoire may be affected, and become imprinted by, the transfer of maternal IgG into the fetus. PMID:27289167

Modulation of natural IgM autoantibodies to oxidative stress-related neo-epitopes on apoptotic cells in newborns of mothers with anti-Ro autoimmunity.

PubMed

Grönwall, Caroline; Clancy, Robert M; Getu, Lelise; Lloyd, Katy A; Siegel, Don L; Reed, Joanne H; Buyon, Jill P; Silverman, Gregg J

2016-09-01

At birth, the human immune system already contains substantial levels of polymeric IgM, that include autoantibodies to neo-epitopes on apoptotic cells (ACs) that are proposed to play homeostatic and anti-inflammatory roles. Yet the biologic origins and developmental regulation of these naturally arising antibodies remain poorly understood. Herein, we report that levels of IgM-antibodies to malondialdehyde (MDA) protein adducts, a common type of in vivo generated oxidative stress-related neoepitope, directly correlate with the relative binding of neonatal-IgM to ACs. Levels of IgM to phosphorylcholine (PC), a natural antibody prevalent in adults, were relatively scant in cord blood, while there was significantly greater relative representation of IgM anti-MDA antibodies in newborns compared to adults. To investigate the potential interrelationships between neonatal IgM with pathogenic IgG-autoantibodies, we studied 103 newborns born to autoimmune mothers with IgG anti-Ro (i.e., 70 with neonatal lupus and 33 without neonatal lupus). In these subjects the mean levels of IgM anti-Ro60 were significantly higher than in the newborns from non-autoimmune mothers. In contrast, levels of IgM anti-MDA in IgG anti-Ro exposed neonates were significantly lower than in neonates from non-autoimmune mothers. The presence or absence of neonatal lupus did not appear to influence the total levels of IgM in the anti-Ro exposed newborns. Taken together, our studies provide evidence that the immune development of the natural IgM-repertoire may be affected, and become imprinted by, the transfer of maternal IgG into the fetus. Copyright © 2016 Elsevier Ltd. All rights reserved.

Oxidized low-density lipoprotein in children with familial hypercholesterolemia and unaffected siblings: effect of pravastatin.

PubMed

Rodenburg, Jessica; Vissers, Maud N; Wiegman, Albert; Miller, Elizabeth R; Ridker, Paul M; Witztum, Joseph L; Kastelein, John J P; Tsimikas, Sotirios

2006-05-02

To assess the role of oxidized phospholipids (OxPLs) in children with familial hypercholesterolemia (FH) and the effect of pravastatin. Oxidized phospholipids are a major component of oxidized low-density lipoprotein (OxLDL) and are bound to lipoprotein (a) [Lp(a)]. The significance of OxPL markers in children is unknown. Children with FH were randomized to placebo (n = 88) or pravastatin (n = 90) after instruction on American Heart Association step II diet. Unaffected siblings (n = 78) served as controls. The OxPL content on apolipoprotein B-100 (apoB) detected by antibody E06 (OxPL/apoB ratio), immunoglobulin (Ig)G and IgM immune complexes per apoB (IC/apoB) and on all apoB particles (total apoB-IC = IC/apoB multiplied by plasma apoB levels), autoantibodies to malondialdehyde (MDA)-low-density lipoprotein (LDL), Lp(a), and apoB levels were measured at baseline and after two years of treatment. Compared with unaffected siblings, children with FH had significantly lower levels of OxPL/apoB but higher levels of IgG and IgM total apoB-IC and IgM MDA-LDL autoantibodies. From baseline to two-year follow-up, compared with placebo pravastatin treatment resulted in a greater mean percentage change in apoB (-18.7% vs. 0.3%; p = 0.001), total IgG apoB-IC (-31.9% vs. -12.2%; p < 0.001), and total IgM apoB-IC (-25.5% vs. 13.2%; p = 0.001). Interestingly, pravastatin also resulted in higher OxPL/apoB (48.7% vs. 29.3%; p = 0.028) and Lp(a) levels (21.9% vs. 10.7%; p = 0.044). Compared with unaffected siblings, children with FH are characterized by elevated levels of apoB-IC and IgM MDA-LDL autoantibodies. Compared with placebo, pravastatin led to a greater reduction in apoB-IC but also to a greater increase in OxPL/apoB and Lp(a), which may represent a novel mechanism of mobilization and clearance of OxPL.

Neuron-derived IgG protects dopaminergic neurons from insult by 6-OHDA and activates microglia through the FcγR I and TLR4 pathways.

PubMed

Zhang, Jie; Niu, Na; Wang, Mingyu; McNutt, Michael A; Zhang, Donghong; Zhang, Baogang; Lu, Shijun; Liu, Yuqing; Liu, Zhihui

2013-08-01

Oxidative and immune attacks from the environment or microglia have been implicated in the loss of dopaminergic neurons of Parkinson's disease. The role of IgG which is an important immunologic molecule in the process of Parkinson's disease has been unclear. Evidence suggests that IgG can be produced by neurons in addition to its traditionally recognized source B lymphocytes, but its function in neurons is poorly understood. In this study, extensive expression of neuron-derived IgG was demonstrated in dopaminergic neurons of human and rat mesencephalon. With an in vitro Parkinson's disease model, we found that neuron-derived IgG can improve the survival and reduce apoptosis of dopaminergic neurons induced by 6-hydroxydopamine toxicity, and also depress the release of NO from microglia triggered by 6-hydroxydopamine. Expression of TNF-α and IL-10 in microglia was elevated to protective levels by neuron-derived IgG at a physiologic level via the FcγR I and TLR4 pathways and microglial activation could be attenuated by IgG blocking. All these data suggested that neuron-derived IgG may exert a self-protective function by activating microglia properly, and IgG may be involved in maintaining immunity homeostasis in the central nervous system and serve as an active factor under pathological conditions such as Parkinson's disease. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Allergen-specific IgG antibodies purified from mite-allergic patients sera block the IgE recognition of Dermatophagoides pteronyssinus antigens: an in vitro study.

PubMed

Siman, Isabella Lima; de Aquino, Lais Martins; Ynoue, Leandro Hideki; Miranda, Juliana Silva; Pajuaba, Ana Claudia Arantes Marquez; Cunha-Júnior, Jair Pereira; Silva, Deise Aparecida Oliveira; Taketomi, Ernesto Akio

2013-01-01

One of the purposes of specific immunotherapy (SIT) is to modulate humoral immune response against allergens with significant increases in allergen-specific IgG levels, commonly associated with blocking activity. The present study investigated in vitro blocking activity of allergen-specific IgG antibodies on IgE reactivity to Dermatophagoides pteronyssinus (Dpt) in sera from atopic patients. Dpt-specific IgG antibodies were purified by ammonium sulfate precipitation followed by protein-G affinity chromatography. Purity was checked by SDS-PAGE and immunoreactivity by slot-blot and immunoblot assays. The blocking activity was evaluated by inhibition ELISA. The electrophoretic profile of the ammonium sulfate precipitated fraction showed strongly stained bands in ligand fraction after chromatography, compatible with molecular weight of human whole IgG molecule. The purity degree was confirmed by detecting strong immunoreactivity to IgG, negligible to IgA, and no reactivity to IgE and IgM. Dpt-specific IgG fraction was capable of significantly reducing levels of IgE anti-Dpt, resulting in 35%-51% inhibition of IgE reactivity to Dpt in atopic patients sera. This study showed that allergen-specific IgG antibodies purified from mite-allergic patients sera block the IgE recognition of Dermatophagoides pteronyssinus antigens. This approach reinforces that intermittent measurement of serum allergen-specific IgG antibodies will be an important objective laboratorial parameter that will help specialists to follow their patients under SIT.

IgG4-Related Kidney Disease: Report of a Case Presenting as a Renal Mass

PubMed Central

Topazio, Luca; Gaziev, Gabriele; Iacovelli, Valerio; Bove, Pierluigi; Mauriello, Alessandro; Finazzi Agrò, Enrico

2017-01-01

IgG4-related disease (IgG4-RD) is a nosological entity defined as a chronic immune-mediated fibro-inflammatory condition characterized by a tendency to form tumefactive, tissue-destructive lesions or by organ failure. Urologic involvement in IgG4-RD has been described in some short series of patients and in isolated case reports, most often involving the kidneys in so-called IgG4-related kidney disease (IgG4-RKD). The disease can occasionally mimic malignancies and is at risk of being misdiagnosed due to its rarity. We report the case of a 56-year-old man presenting with a right renal mass suspected of being malignant. Laboratory tests showed normal creatinine levels, a high erythrocyte sedimentation rate, and high levels of C-reactive protein and microalbuminuria. The patient underwent radical right nephroureterectomy and histopathologic examination revealed features proving IgG4-RKD. He was therefore referred to immunologists. Typical clinical presentation of IgG4-RKD includes altered renal function with inconstant or no radiologic findings. Conversely, in the case we presented, a single nodule was detected upon imaging evaluation, thus mimicking malignancy. This raises the issue of a proper differential diagnosis. A multidisciplinary approach can be useful, although in clinical practice the selection of patients suspected of having IgG4-RKD is critical in the cases presenting with a renal mass that mimics malignancy. PMID:28912998

Serological and molecular analysis of parvovirus B19 infection in Mayan women with systemic lupus erythematosus in Mexico.

PubMed

Valencia Pacheco, Guillermo; Nakazawa Ueji, Yumi E; Rodríguez Dzul, Edwin A; Angulo Ramírez, Angélica V; López Villanueva, Ricardo F; Quintal Ortiz, Irma G; Rosado Paredes, Elsy P

2017-09-30

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that mainly affects women, characterized by the production of autoantibodies. Its causal agent is unknown, but the combination of environmental, hormonal and genetic factors may favor the development of the disease. Parvovirus B19 has been associated with the development of SLE, since it induces the production of anti-single stranded DNA antibodies. It is unknown whether PV-B19 infection is an environmental factor that trigger or reactivate SLE in the Mexican Mayan population. A preliminary serological and molecular study of PV-B19 infection in Mayan women with established SLE was done. IgG and IgM anti PV-B19 were evaluated in 66 SLE patients and 66 control subjects, all women of Mayan origin. Viral DNA and viral load were analyzed by qPCR. Insignificant levels of IgM were observed in 14.3% (4/28) of the patients and 11.4% (4/35) of control subjects. IgG was detected in 82.1% (23/28) of the patients and 82.9% (29/35) of control subjects, but were significantly higher in patients. Viral DNA was found in 86.0% (57/66) of the patients and 81.0% (54/66) of control subjects. Viral load, quantified in 28/66 patients and 31/66 controls which were positive for IgM and IgG, was significantly higher in controls. The high prevalence of PV-B19 in Yucatan, and the presence of IgM, IgG, and viral load in Mayan women with established SLE suggest that PV-B19 infection could be an environmental factor to trigger or reactivate SLE.

Elevated Immune Response Among Children 4 Years of Age With Pronounced Local Adverse Events After the Fifth Diphtheria, Tetanus, Acellular Pertussis Vaccination.

PubMed

van der Lee, Saskia; Kemmeren, Jeanet M; de Rond, Lia G H; Öztürk, Kemal; Westerhof, Anneke; de Melker, Hester E; Sanders, Elisabeth A M; Berbers, Guy A M; van der Maas, Nicoline A T; Rümke, Hans C; Buisman, Anne-Marie

2017-09-01

In the Netherlands, acellular pertussis vaccines replaced the more reactogenic whole-cell pertussis vaccines. This replacement in the primary immunization schedule of infants coincided with a significant increase in pronounced local adverse events (AEs) in 4 years old children shortly after the administration of a fifth diphtheria, tetanus, acellular pertussis and inactivated polio (DTaP-IPV) vaccine. The objective of this study was to investigate possible differences in vaccine antigen-specific immune responses between children with and without a pronounced local AE after the fifth DTaP-IPV vaccination. Blood was sampled in 2 groups of 4-year-olds: a case group reporting pronounced local swelling and/or erythema up to extensive limb swelling at the injection site (n = 30) and a control group (n = 30). Peripheral blood mononuclear cells were stimulated with individual vaccine antigens. Plasma antigen-specific IgG, IgG subclass and total IgE concentrations and T-cell cytokine [interferon-gamma, interleukin (IL)-13, IL-17 and IL-10] production by stimulated peripheral blood mononuclear cells were determined by multiplex bead-based fluorescent multiplex immunoassays. In children with AEs, significantly higher total IgE and vaccine antigen-specific IgG and IgG4 responses as well as levels of the T-helper 2 (Th2) cytokine IL-13 were found after pertussis, tetanus and diphtheria stimulation compared with controls. Children with pronounced local reactions show higher humoral and cellular immune responses. Acellular vaccines are known to skew toward more Th2 responses. The pronounced local AEs may be associated with more Th2 skewing after the fifth DTaP-IPV vaccination, but other biologic factors may also impact the occurrence of these pronounced local reactions.

Serological and molecular analysis of parvovirus B19 infection in Mayan women with systemic lupus erythematosus in Mexico

PubMed Central

Nakazawa Ueji, Yumi E; Rodríguez Dzul, Edwin A; Angulo Ramírez, Angélica V; López Villanueva, Ricardo F; Quintal Ortiz, Irma G; Rosado Paredes, Elsy P

2017-01-01

Abstract Background: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that mainly affects women, characterized by the production of autoantibodies. Its causal agent is unknown, but the combination of environmental, hormonal and genetic factors may favor the development of the disease. Parvovirus B19 has been associated with the development of SLE, since it induces the production of anti-single stranded DNA antibodies. It is unknown whether PV-B19 infection is an environmental factor that trigger or reactivate SLE in the Mexican Mayan population. Aim: A preliminary serological and molecular study of PV-B19 infection in Mayan women with established SLE was done. Methods: IgG and IgM anti PV-B19 were evaluated in 66 SLE patients and 66 control subjects, all women of Mayan origin. Viral DNA and viral load were analyzed by qPCR. Results: Insignificant levels of IgM were observed in 14.3% (4/28) of the patients and 11.4% (4/35) of control subjects. IgG was detected in 82.1% (23/28) of the patients and 82.9% (29/35) of control subjects, but were significantly higher in patients. Viral DNA was found in 86.0% (57/66) of the patients and 81.0% (54/66) of control subjects. Viral load, quantified in 28/66 patients and 31/66 controls which were positive for IgM and IgG, was significantly higher in controls. Conclusion: The high prevalence of PV-B19 in Yucatan, and the presence of IgM, IgG, and viral load in Mayan women with established SLE suggest that PV-B19 infection could be an environmental factor to trigger or reactivate SLE. PMID:29213152

Serum IgG and IgA levels in polio and non-polio acute flaccid paralysis cases in western Uttar Pradesh, India.

PubMed

Mohanty, Madhu C; Nalavade, Uma P; Deshpande, Jagadish M

2015-03-08

IgG and IgA immunocompetence of children with wild poliovirus poliomyelitis and non-polio acute flaccid paralysis. 932 cases of acute flaccid paralysis, reported in 2008-2009, were tested for presence of polio and non-polio enteroviruses according to the WHO standards. Serum IgA and IgG levels were determined by sandwich ELISA. Mean (SD) IgA levels [0.87 (0.62)g/L; n=28] of virologically confirmed poliomyelitis cases were lower than those of virus negative [1.21 (0.83)g/L; n=612] and non-polio Enterovirus positive [1.22 (0.79)g/L; n=240] cases of acute flaccid paralysis. No significant difference was observed in the concentration of IgG among these groups. IgA plays an important role in protection against poliomyelitis.

The neonatal Fc receptor (FcRn) binds independently to both sites of the IgG homodimer with identical affinity.

PubMed

Abdiche, Yasmina Noubia; Yeung, Yik Andy; Chaparro-Riggers, Javier; Barman, Ishita; Strop, Pavel; Chin, Sherman Michael; Pham, Amber; Bolton, Gary; McDonough, Dan; Lindquist, Kevin; Pons, Jaume; Rajpal, Arvind

2015-01-01

The neonatal Fc receptor (FcRn) is expressed by cells of epithelial, endothelial and myeloid lineages and performs multiple roles in adaptive immunity. Characterizing the FcRn/IgG interaction is fundamental to designing therapeutic antibodies because IgGs with moderately increased binding affinities for FcRn exhibit superior serum half-lives and efficacy. It has been hypothesized that 2 FcRn molecules bind an IgG homodimer with disparate affinities, yet their affinity constants are inconsistent across the literature. Using surface plasmon resonance biosensor assays that eliminated confounding experimental artifacts, we present data supporting an alternate hypothesis: 2 FcRn molecules saturate an IgG homodimer with identical affinities at independent sites, consistent with the symmetrical arrangement of the FcRn/Fc complex observed in the crystal structure published by Burmeister et al. in 1994. We find that human FcRn binds human IgG1 with an equilibrium dissociation constant (KD) of 760 ± 60 nM (N = 14) at 25°C and pH 5.8, and shows less than 25% variation across the other human subtypes. Human IgG1 binds cynomolgus monkey FcRn with a 2-fold higher affinity than human FcRn, and binds both mouse and rat FcRn with a 10-fold higher affinity than human FcRn. FcRn/IgG interactions from multiple species show less than a 2-fold weaker affinity at 37°C than at 25°C and appear independent of an IgG's variable region. Our in vivo data in mouse and rat models demonstrate that both affinity and avidity influence an IgG's serum half-life, which should be considered when choosing animals, especially transgenic systems, as surrogates.

Characterization and screening of IgG binding to the neonatal Fc receptor

PubMed Central

Neuber, Tobias; Frese, Katrin; Jaehrling, Jan; Jäger, Sebastian; Daubert, Daniela; Felderer, Karin; Linnemann, Mechthild; Höhne, Anne; Kaden, Stefan; Kölln, Johanna; Tiller, Thomas; Brocks, Bodo; Ostendorp, Ralf; Pabst, Stefan

2014-01-01

The neonatal Fc receptor (FcRn) protects immunoglobulin G (IgG) from degradation and increases the serum half-life of IgG, thereby contributing to a higher concentration of IgG in the serum. Because altered FcRn binding may result in a reduced or prolonged half-life of IgG molecules, it is advisable to characterize Fc receptor binding of therapeutic antibody lead candidates prior to the start of pre-clinical and clinical studies. In this study, we characterized the interactions between FcRn of different species (human, cynomolgus monkey, mouse and rat) and nine IgG molecules from different species and isotypes with common variable heavy (VH) and variable light chain (VL) domains. Binding was analyzed at acidic and neutral pH using surface plasmon resonance (SPR) and biolayer interferometry (BLI). Furthermore, we transferred the well-accepted, but low throughput SPR-based method for FcRn binding characterization to the BLI-based Octet platform to enable a higher sample throughput allowing the characterization of FcRn binding already during early drug discovery phase. We showed that the BLI-based approach is fit-for-purpose and capable of discriminating between IgG molecules with significant differences in FcRn binding affinities. Using this high-throughput approach we investigated FcRn binding of 36 IgG molecules that represented all VH/VL region combinations available in the fully human, recombinant antibody library Ylanthia®. Our results clearly showed normal FcRn binding profiles for all samples. Hence, the variations among the framework parts, complementarity-determining region (CDR) 1 and CDR2 of the fragment antigen binding (Fab) domain did not significantly change FcRn binding. PMID:24802048

Analysis of ovine colostrum to detect antibody against progressive pneumonia virus.

PubMed Central

Taylor, T B; Banowetz, G M; Schipper, I A; Gabrielson, D A

1982-01-01

Immunoglobulins were isolated and purified from the colostrum and serum of progressive pneumonia virus infected sheep and also from non-infected control sheep. Four classes of immunoglobulins were isolated from sheep colostrum (IgG1, IgG2, IgA and Ig10s). Three classes of immunoglobulins were isolated from sheep serum (IgG1, IgG2 and IgM). Low levels of virus neutralizing activity were demonstrated only in the whole serum and purified serum IgG1 preparations. No complement fixing activity was detected in any of the antibody preparations from colostrum. PMID:6284323

Macrophage-derived insulin-like growth factor-1 affects influenza vaccine efficacy through the regulation of immune cell homeostasis.

PubMed

Yoon, Il-Sub; Park, Hyelim; Kwak, Hye-Won; Woo Jung, Yong; Nam, Jae-Hwan

2017-08-24

The level of antibody production induced by a vaccine involves a variety of host factors. One of these, insulin-like growth factor-1 (IGF-1), plays an important role in lymphocyte maturation and antibody expression. Here, we investigated the role of macrophage-derived IGF-1 in the induction of influenza vaccine-specific antibodies using macrophage-derived IGF-1 gene knockout (MIKO) mice. The titers of vaccine-specific total immunoglobulin G (IgG) and IgG1 after immunization were about two- to fourfold lower in MIKO mice than in WT mice. Moreover, MIKO mice showed a relatively weak booster effect of repeated immunization. In contrast, antigen-nonspecific total IgG was about threefold higher in MIKO mice than in WT mice. After viral challenge, the viral titer and the pathological damage in lungs of MIKO mice were higher than those in WT mice despite vaccination. Interestingly, the proportions of proinflammatory immune cells including M1 macrophages, Th1 and Th17 cells was higher in unvaccinated MIKO mice than in unvaccinated WT mice. This suggests that nonspecific activation of immune cells may paradoxically impair the response to the vaccine. In addition, although the proportions of T follicular helper (Tfh) cells and GL-7 + germinal center (GC) B cells were higher in MIKO mice than in WT mice, the population of CD138 + B220 + antibody-secreting plasmablasts was lower in MIKO mice, which may be a cause of the low influenza-specific antibody titer in MIKO mice. Taken together, these results suggest that macrophage-derived IGF-1 might play an important role in the vaccine-triggered immune response by regulating immune cell homeostasis. Copyright © 2017 Elsevier Ltd. All rights reserved.

CSF cytokine profile in MOG-IgG+ neurological disease is similar to AQP4-IgG+ NMOSD but distinct from MS: a cross-sectional study and potential therapeutic implications.

PubMed

Kaneko, Kimihiko; Sato, Douglas Kazutoshi; Nakashima, Ichiro; Ogawa, Ryo; Akaishi, Tetsuya; Takai, Yoshiki; Nishiyama, Shuhei; Takahashi, Toshiyuki; Misu, Tatsuro; Kuroda, Hiroshi; Tanaka, Satoru; Nomura, Kyoichi; Hashimoto, Yuji; Callegaro, Dagoberto; Steinman, Lawrence; Fujihara, Kazuo; Aoki, Masashi

2018-06-06

To evaluate cerebrospinal fluid (CSF) cytokine profiles in myelin oligodendrocyte glycoprotein IgG-positive (MOG-IgG+) disease in adult and paediatric patients. In this cross-sectional study, we measured 27 cytokines in the CSF of MOG-IgG+ disease in acute phase before treatment (n=29). The data were directly compared with those in aquaporin-4 antibody-positive (AQP4-IgG+) neuromyelitis optica spectrum disorder (NMOSD) (n=20), multiple sclerosis (MS) (n=20) and non-inflammatory controls (n=14). In MOG-IgG+ disease, there was no female preponderance and the ages were younger (mean 18 years, range 3-68; 15 were below 18 years) relative to AQP4-IgG+ NMOSD (41, 15-77) and MS (34, 17-48). CSF cell counts were higher and oligoclonal IgG bands were mostly negative in MOG-IgG+ disease and AQP4-IgG+ NMOSD compared with MS. MOG-IgG+ disease had significantly elevated levels of interleukin (IL)-6, IL-8, granulocyte-colony stimulating factor and granulocyte macrophage-colony stimulating factor, interferon-γ, IL-10, IL-1 receptor antagonist, monocyte chemotactic protein-1 and macrophage inflammatory protein-1α as compared with MS. No cytokine in MOG-IgG+ disease was significantly different from AQP4-IgG+ NMOSD. Moreover many elevated cytokines were correlated with each other in MOG-IgG+ disease and AQP4-IgG+ NMOSD but not in MS. No difference in the data was seen between adult and paediatric MOG-IgG+ cases. The CSF cytokine profile in the acute phase of MOG-IgG+ disease is characterised by coordinated upregulation of T helper 17 (Th17) and other cytokines including some Th1-related and regulatory T cells-related ones in adults and children, which is similar to AQP4-IgG+ NMOSD but clearly different from MS. The results suggest that as with AQP4-IgG+ NMOSD, some disease-modifying drugs for MS may be ineffective in MOG-IgG+ disease while they may provide potential therapeutic targets. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

IL-27 induces the production of IgG1 by human B cells.

PubMed

Boumendjel, Amel; Tawk, Lina; Malefijt, René de Waal; Boulay, Vera; Yssel, Hans; Pène, Jérôme

2006-12-01

It has been reported that IL-27 specifically induces the production of IgG2a by mouse B cells and inhibits IL-4-induced IgG1 synthesis. Here, we show that human naïve cord blood expresses a functional IL-27 receptor, consisting of the TCCR and gp130 subunits, although at lower levels as compared to naïve and memory splenic B cells. IL-27 does not induce proliferative responses and does not increase IgG1 production by CD19(+)CD27(+) memory B cells. However, it induces a low, but significant production of IgG1 by naïve CD19(+)CD27(-)IgD(+)IgG(-) spleen and cord blood B cells, activated via CD40, whereas it has no effect on the production of the other IgG subclasses. In addition, IL-27 induces the differentiation of a population of B cells that express high levels of CD38, in association with a down-regulation of surface IgD expression, and that are surface IgG(+/int), CD20(low), CD27(high), indicating that IL-27 promotes isotype switching and plasma cell differentiation of naive B cells. However, as compared to the effects of IL-21 and IL-10, both switch factors for human IgG1 and IgG3, those of IL-27 are modest and regulate exclusively the production of IgG1. Finally, although IL-27 has no effect on IL-4 and anti-CD40-induced Cepsilon germline promoter activity, it up-regulates IL-4-induced IgE production by naive B cells. These results point to a partial redundancy of switch factors regulating the production of IgG1 in humans, and furthermore indicate the existence of a common regulation of the human IgG1and murine IgG2a isotypes by IL-27.

Single Nucleotide Polymorphisms in P2X7 Gene Are Associated with Serum Immunoglobulin G Responses to Mycobacterium tuberculosis in Tuberculosis Patients

PubMed Central

Wu, Jiangdong; Lu, Lijun; Zhang, Le; Ding, Yulei; Wu, Fang; Zuo, Weize; Zhang, Wanjiang

2015-01-01

Objective. Our study investigated the association between single nucleotide polymorphisms (SNPs) in P2X7 gene and serum immunoglobulin G (IgG) responses to mycobacterium tuberculosis (MTB) in TB patients. Methods. A total of 103 TB patients were enrolled as case group and 87 healthy individuals at same geographical region as control group. The SNP detection of 1513A>C and -762T>C was performed using PCR-RFLP, and the levels of serum IgG responses to MTB in all subjects were determined. Results. AC and CC of 1513A>C and TC and CC of -762T>C had higher frequencies in case group than in control group. TB patients carrying TC and CC of -762T>C had higher positive rate of IgG responses to MTB than those carrying TT. Additionally, patients carrying TC and CC of -762T>C had more MTB in sputum than those carrying TT. Conclusion. P2X7 SNPs, 1513A>C and -762T>C, may be associated with the susceptibility to tuberculosis, and -762T>C SNP may contribute to the development of MTB. The mutant genotype of -762T>C (TC and CC) may lower human capability of phagocytosis to MTB, leading to an increased morbidity of TB. PMID:26798189

Dynamics of the serologic response in vaccinated and unvaccinated mumps cases during an epidemic.

PubMed

Kaaijk, Patricia; Gouma, Sigrid; Hulscher, Hinke I; Han, Wanda G; Kleijne, Deborah E; van Binnendijk, Rob S; van Els, Cécile A

2015-01-01

In the last decade, several mumps outbreaks were reported in various countries despite high vaccination coverage. In most cases, young adults were affected who have acquired immunity against mumps solely by vaccination and not by previous wild-type mumps virus infection. To investigate mumps-specific antibody levels, functionality and dynamics during a mumps epidemic, blood samples were obtained longitudinally from 23 clinical mumps cases, with or without a prior history of vaccination, and from 20 healthy persons with no serological evidence of recent mumps virus infection. Blood samples from mumps cases were taken 1-2 months and 7-10 months after onset of disease. Both vaccinated and unvaccinated mumps cases had significantly higher geomean concentrations of mumps-specific IgG (resp. 13,617 RU/ml (95% CI of 9,574-19,367 RU/ml) vs. 1,552 (445-5412) RU/ml at 1-2 months; and 6,514 (5,247-8,088) RU/ml vs. 1,143 (480-2,725) RU/ml at 7-10 months) than healthy controls (169 (135-210) RU/ml) (p = 0.001). Patterns in virus-neutralizing (VN) antibody responses against the mumps vaccine virus were similar, vaccinated and unvaccinated mumps cases had significantly higher ND50 values at both time points of sampling (resp 4,695 (3,779-5,832) RU/ml vs. 1,533 (832-2,825) RU/ml at 1-2 months; 2,478 (1,968-3,122) RU/ml vs. 1,221 (1,029-1,449) RU/ml at 7-10 months) compared with (previously vaccinated) healthy controls (122 (196-76)) RU/ml) (p = 0.001) The unvaccinated mumps cases had significantly lower mumps-specific IgG and VN antibody concentrations at both sampling points compared with previously vaccinated cases, but their antibody concentrations did not differ significantly at the 2 time points. In contrast, the mumps-specific IgG and VN antibody concentrations of the previously vaccinated mumps cases were significantly higher within the first 2 months after onset of mumps and declined thereafter, characteristic for a secondary response. A moderate correlation was found between the level of mumps-specific IgG serum antibodies and VN antibodies for the mumps cases (r = 0.64; p<0.001).

Dynamics of the serologic response in vaccinated and unvaccinated mumps cases during an epidemic

PubMed Central

Kaaijk, Patricia; Gouma, Sigrid; Hulscher, Hinke I; Han, Wanda G; Kleijne, Deborah E; van Binnendijk, Rob S; van Els, Cécile A

2015-01-01

In the last decade, several mumps outbreaks were reported in various countries despite high vaccination coverage. In most cases, young adults were affected who have acquired immunity against mumps solely by vaccination and not by previous wild-type mumps virus infection. To investigate mumps-specific antibody levels, functionality and dynamics during a mumps epidemic, blood samples were obtained longitudinally from 23 clinical mumps cases, with or without a prior history of vaccination, and from 20 healthy persons with no serological evidence of recent mumps virus infection. Blood samples from mumps cases were taken 1–2 months and 7–10 months after onset of disease. Both vaccinated and unvaccinated mumps cases had significantly higher geomean concentrations of mumps-specific IgG (resp. 13,617 RU/ml (95% CI of 9,574–19,367 RU/ml) vs. 1,552 (445–5412) RU/ml at 1–2 months; and 6,514 (5,247–8,088) RU/ml vs. 1,143 (480–2,725) RU/ml at 7–10 months) than healthy controls (169 (135–210) RU/ml) (p = 0.001). Patterns in virus-neutralizing (VN) antibody responses against the mumps vaccine virus were similar, vaccinated and unvaccinated mumps cases had significantly higher ND50 values at both time points of sampling (resp 4,695 (3,779–5,832) RU/ml vs. 1,533 (832–2,825) RU/ml at 1–2 months; 2,478 (1,968–3,122) RU/ml vs. 1,221 (1,029–1,449) RU/ml at 7–10 months) compared with (previously vaccinated) healthy controls (122 (196–76)) RU/ml) (p = 0.001) The unvaccinated mumps cases had significantly lower mumps-specific IgG and VN antibody concentrations at both sampling points compared with previously vaccinated cases, but their antibody concentrations did not differ significantly at the 2 time points. In contrast, the mumps-specific IgG and VN antibody concentrations of the previously vaccinated mumps cases were significantly higher within the first 2 months after onset of mumps and declined thereafter, characteristic for a secondary response. A moderate correlation was found between the level of mumps-specific IgG serum antibodies and VN antibodies for the mumps cases (r = 0.64; p<0.001). PMID:26047038

Metal Ion Interactions with Immunoglobulin G (IgG). 1. Preliminary Studies with Electron Paramagnetic Resonance (EPR) Spectroscopy and Ultrafiltration

DTIC Science & Technology

1978-12-12

EPR and ultrafiltration studies are recommceided to conduct luture metal ion- IgG binding research. Using Scatchard plots, bind.ng levels can be...of the binding sites can be best pursued by EPR and ultrafiltration using the fragments of IgG . This report noted some difference in the binding...immunoelectrophoresis, ultrafiltration, UV spectroscopy, atomic absorption spectroscopy, and electron paramagnetic resonance (EPR). IgG used ,- ,is non

Structural basis for pH-insensitive inhibition of immunoglobulin G recycling by an anti-neonatal Fc receptor antibody

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kenniston, Jon A.; Taylor, Brandy M.; Conley, Gregory P.

The neonatal Fc receptor FcRn plays a critical role in the trafficking of IgGs across tissue barriers and in retaining high circulating concentrations of both IgG and albumin. Although generally beneficial from an immunological perspective in maintaining IgG populations, FcRn can contribute to the pathogenesis of autoimmune disorders when an abnormal immune response targets normal biological components. We previously described a monoclonal antibody (DX-2507) that binds to FcRn with high affinity at both neutral and acidic pH, prevents the simultaneous binding of IgG, and reduces circulating IgG levels in preclinical animal models. Here, we report a 2.5 Å resolution X-raymore » crystal structure of an FcRn–DX-2507 Fab complex, revealing a nearly complete overlap of the IgG–Fc binding site in FcRn by complementarity-determining regions in DX-2507. This overlap explains how DX-2507 blocks IgG binding to FcRn and thereby shortens IgG half-life by preventing IgGs from recycling back into circulation. Moreover, the complex structure explains how the DX-2507 interaction is pH-insensitive unlike normal Fc interactions and how serum albumin levels are unaffected by DX-2507 binding. These structural studies could inform antibody-based therapeutic approaches for limiting the effects of IgG-mediated autoimmune disease.« less

Highly sensitive detection of human IgG using a novel bio-barcode assay combined with DNA chip technology

NASA Astrophysics Data System (ADS)

Liu, Zhenbao; Zhou, Bo; Wang, Haiqing; Lu, Feng; Liu, Tianjun; Song, Cunxian; Leng, Xigang

2013-09-01

A simple and ultrasensitive detection of human IgG based on signal amplification using a novel bio-barcode assay and DNA chip technology was developed. The sensing platform was a sandwich system made up of antibody-modified magnetic microparticles (Ab-MMPs)/human IgG/Cy3-labeled single-stranded DNA and antibody-modified gold nanoparticles (Cy3-ssDNA-Ab-AuNPs). The MMPs (2.5 μm in diameter) modified with mouse anti-human IgG monoclonal-antibodies could capture human IgG and further be separated and enriched via a magnetic field. The AuNPs (13 nm in diameter) conjugated with goat anti-human IgG polyclonal-antibodies and Cy3-ssDNA could further combine with the human IgG/Ab-MMP complex. The Cy3-ssDNA on AuNPs was then released by TCEP to hybridize with the DNA chip, thus generating a detectable signal by the fluorescence intensity of Cy3. In order to improve detection sensitivity, a three-level cascaded signal amplification was developed: (1) The MMP enrichment as the first-level; (2) Large quantities of Cy3-ssDNA on AuNPs as the second-level; (3) The Cy3-ssDNA conjugate with DNA chip as the third-level. The highly sensitive technique showed an increased response of the fluorescence intensity to the increased concentration of human IgG through a detection range from 1 pg mL-1 to 10 ng mL-1. This sensing technique could not only improve the detection sensitivity for the low concentration of human IgG but also present a robust and efficient signal amplification model. The detection method has good stability, specificity, and reproducibility and could be applied in the detection of human IgG in the real samples.

Quantitative measurement of human thyroglobulin-specific antibodies by use of a sensitive enzyme-linked immunoassay.

PubMed

Kuppers, R C; Outschoorn, I M; Hamilton, R G; Burek, C L; Rose, N R

1993-04-01

A quantitative enzyme-linked immunoassay that measures in absolute terms the subclass concentration of human thyroglobulin (huTg)-specific IgG autoantibody was developed. Unique to this study was the use of an affinity-purified anti-huTg standard with a known concentration of the four IgG subclasses. The sensitivity of the ELISA assay was 1-5 ng/ml depending on the IgG subclass being measured. We examined 22 sera of patients with autoimmune thyroid disease. The total huTg-specific antibody concentrations in serum ranged from 0 to nearly 3000 micrograms/ml of IgG. The IgG subclass distribution in individuals with low huTg-specific IgG (< 10 micrograms/ml) was primarily IgG1 and IgG3 Ab. Patients with intermediate levels of huTg IgG (10-600 micrograms/ml) expressed all four subclasses; however, no particular subclass was dominant. Individuals with > 1000 micrograms/ml also showed huTg-Ab in all four subclasses, however, IgG1 and IgG2 were dominant. All four IgG subclasses were used in the response to huTg, although the pattern of usage varied between individuals. There was no dominant subclass usage seen in this patient population.

Anti-LRP/LR Specific Antibody IgG1-iS18 Impedes Adhesion and Invasion of Liver Cancer Cells

PubMed Central

Chetty, Carryn; Khumalo, Thandokuhle; Da Costa Dias, Bianca; Reusch, Uwe; Knackmuss, Stefan; Little, Melvyn; Weiss, Stefan F. T.

2014-01-01

Two key events, namely adhesion and invasion, are pivotal to the occurrence of metastasis. Importantly, the 37 kDa/67 kDa laminin receptor (LRP/LR) has been implicated in enhancing these two events thus facilitating cancer progression. In the current study, the role of LRP/LR in the adhesion and invasion of liver cancer (HUH-7) and leukaemia (K562) cells was investigated. Flow cytometry revealed that the HUH-7 cells displayed significantly higher cell surface LRP/LR levels compared to the poorly-invasive breast cancer (MCF-7) control cells, whilst the K562 cells displayed significantly lower cell surface LRP/LR levels in comparison to the MCF-7 control cells. However, Western blotting and densitometric analysis revealed that all three tumorigenic cell lines did not differ significantly with regards to total LRP/LR levels. Furthermore, treatment of liver cancer cells with anti-LRP/LR specific antibody IgG1-iS18 (0.2 mg/ml) significantly reduced the adhesive potential of cells to laminin-1 and the invasive potential of cells through the ECM-like Matrigel, whilst leukaemia cells showed no significant differences in both instances. Additionally, Pearson's correlation coefficients suggested direct proportionality between cell surface LRP/LR levels and the adhesive and invasive potential of liver cancer and leukaemia cells. These findings suggest the potential use of anti-LRP/LR specific antibody IgG1-iS18 as an alternative therapeutic tool for metastatic liver cancer through impediment of the LRP/LR- laminin-1 interaction. PMID:24798101

Seroepidemiology of helicobacter pylori infection in pregnant women in rural durango, Mexico.

PubMed

Alvarado-Esquivel, Cosme

2013-12-01

The seroepidemiology of Helicobacter pylori infection in pregnant women in Durango, Mexico is largely unknown. The prevalence of anti-H. pylori IgG antibodies was examined in 343 pregnant women living in rural areas in 7 municipalities in Durango State, Mexico, using enzyme-linked immunosorbent assays (ELISA). A correlation of H. pylori seropositivity with socio-demographic, obstetric and behavioral characteristics of pregnant women was also assessed. In total, 179 (52.2%) of the 343 pregnant women (mean age, 24.2 ± 5.9 years) had H. pylori IgG antibodies, 75 (41.9%) of whom had H. pylori IgG antibody levels higher than 100 U/mL. The seroprevalence of H. pylori infection varied from 33.3% to 65% among municipalities. In contrast, the seroprevalence was comparable among women regardless their age, educational level, occupation, socioeconomic status, animal contacts, foreign travel, eating habits, contact with soil, crowding, sanitary conditions at home and educational level of the head of their families. Multivariant analysis of socio-demographic and behavioral variables showed that H. pylori seropositivity was associated with municipality (OR=1.12; 95% CI: 1.01-1.24; P=0.02). Of the obstetric characteristics, the seroprevalence of H. pylori infection increased significantly with the number of pregnancies and deliveries but not with the number of cesarean sections or miscarriages. Rural pregnant women in Durango had a lower seroprevalence of H. pylori infection than those from populations in developing countries. Results support a variability of H. pylori seroprevalence within a region. Further research at a municipal level might help to understand the epidemiology of H. pylori infection.

The chemiluminescent response of human monocytes to red cells sensitized with monoclonal anti-Rh(D) antibodies.

PubMed

Hadley, A G; Kumpel, B M; Merry, A H

1988-01-01

Luminol-enhanced chemiluminescence (CL) was used to assess the metabolic response of human monocytes to red cells sensitized with known amounts of anti-Rh(D). Monoclonal antibodies were used to facilitate a comparison between the functional activities of IgG1 and IgG3 subclasses. The detection of CL provided a simple, rapid and semi-quantitative means of measuring monocyte response to sensitized red cells (IgG-RBC). Monocyte response to IgG3-RBC was quantitatively greater, more rapid and less susceptible to inhibition by fluid phase IgG than monocyte response to IgG1-RBC. The minimum levels of sensitization required to elicit CL from monocytes were approximately 2500 IgG3 molecules per red cell, or approximately 5000 IgG1 molecules per cell.

HIV-specific Fc effector function early in infection predicts the development of broadly neutralizing antibodies.

PubMed

Richardson, Simone I; Chung, Amy W; Natarajan, Harini; Mabvakure, Batsirai; Mkhize, Nonhlanhla N; Garrett, Nigel; Abdool Karim, Salim; Moore, Penny L; Ackerman, Margaret E; Alter, Galit; Morris, Lynn

2018-04-01

While the induction of broadly neutralizing antibodies (bNAbs) is a major goal of HIV vaccination strategies, there is mounting evidence to suggest that antibodies with Fc effector function also contribute to protection against HIV infection. Here we investigated Fc effector functionality of HIV-specific IgG plasma antibodies over 3 years of infection in 23 individuals, 13 of whom developed bNAbs. Antibody-dependent cellular phagocytosis (ADCP), complement deposition (ADCD), cellular cytotoxicity (ADCC) and cellular trogocytosis (ADCT) were detected in almost all individuals with levels of activity increasing over time. At 6 months post-infection, individuals with bNAbs had significantly higher levels of ADCD and ADCT that correlated with antibody binding to C1q and FcγRIIa respectively. In addition, antibodies from individuals with bNAbs showed more IgG subclass diversity to multiple HIV antigens which also correlated with Fc polyfunctionality. Germinal center activity represented by CXCL13 levels and expression of activation-induced cytidine deaminase (AID) was found to be associated with neutralization breadth, Fc polyfunctionality and IgG subclass diversity. Overall, multivariate analysis by random forest classification was able to group bNAb individuals with 85% sensitivity and 80% specificity based on the properties of their antibody Fc early in HIV infection. Thus, the Fc effector function profile predicted the development of neutralization breadth in this cohort, suggesting that intrinsic immune factors within the germinal center provide a mechanistic link between the Fc and Fab of HIV-specific antibodies.

HIV-specific Fc effector function early in infection predicts the development of broadly neutralizing antibodies

PubMed Central

Richardson, Simone I.; Mabvakure, Batsirai; Mkhize, Nonhlanhla N.; Moore, Penny L.; Alter, Galit

2018-01-01

While the induction of broadly neutralizing antibodies (bNAbs) is a major goal of HIV vaccination strategies, there is mounting evidence to suggest that antibodies with Fc effector function also contribute to protection against HIV infection. Here we investigated Fc effector functionality of HIV-specific IgG plasma antibodies over 3 years of infection in 23 individuals, 13 of whom developed bNAbs. Antibody-dependent cellular phagocytosis (ADCP), complement deposition (ADCD), cellular cytotoxicity (ADCC) and cellular trogocytosis (ADCT) were detected in almost all individuals with levels of activity increasing over time. At 6 months post-infection, individuals with bNAbs had significantly higher levels of ADCD and ADCT that correlated with antibody binding to C1q and FcγRIIa respectively. In addition, antibodies from individuals with bNAbs showed more IgG subclass diversity to multiple HIV antigens which also correlated with Fc polyfunctionality. Germinal center activity represented by CXCL13 levels and expression of activation-induced cytidine deaminase (AID) was found to be associated with neutralization breadth, Fc polyfunctionality and IgG subclass diversity. Overall, multivariate analysis by random forest classification was able to group bNAb individuals with 85% sensitivity and 80% specificity based on the properties of their antibody Fc early in HIV infection. Thus, the Fc effector function profile predicted the development of neutralization breadth in this cohort, suggesting that intrinsic immune factors within the germinal center provide a mechanistic link between the Fc and Fab of HIV-specific antibodies. PMID:29630668

IgG1-iS18 impedes the adhesive and invasive potential of early and late stage malignant melanoma cells.

PubMed

Munien, Carmelle; Rebelo, Thalia M; Ferreira, Eloise; Weiss, Stefan F T

2017-02-15

The 37kDa/67kDa laminin receptor (LRP/LR) is a non-integrin laminin receptor which is overexpressed in tumorigenic cells and supports progression of cancer via promoting metastasis, angiogenesis and telomerase activity and impediment of apoptosis. The present study investigates the role of LRP/LR on the metastatic potential of early (A375) and late (A375SM) stage malignant melanoma cells. Flow cytometry revealed that both early and late stage malignant melanoma cells display high levels of LRP/LR on their cell surface. Flow cytometry and western blot analysis showed that late stage malignant melanoma cells display significantly higher total and cell surface LRP/LR levels in comparison to early stage malignant melanoma cells and the poorly invasive breast cancer (MCF-7) control cell line. Targeting LRP/LR using the LRP/LR specific antibody IgG1-iS18 resulted in a significant reduction of the adhesive potential to laminin-1 and the invasive potential through the 'ECM-simulating' Matrigel™ of both early and late stage malignant melanoma cells. Furthermore, Pearson's correlation coefficient confirmed that increased LRP levels correlate with the increased invasive and adhesive potential in early and late stage melanoma cells. Thus, blocking LRP/LR using the IgG1-iS18 antibody may therefore be a promising therapeutic strategy for early and late stage malignant melanoma treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

Autoantibodies of IgM and IgG classes show differences in recognition of multiple autoantigens in chronic obstructive pulmonary disease.

PubMed

Shindi, Reham; Almehairi, Amna; Negm, Ola H; Kalsheker, Noor; Gale, Nichola S; Shale, Dennis J; Harrison, Timothy W; Bolton, Charlotte E; John, Michelle; Todd, Ian; Tighe, Patrick J; Fairclough, Lucy C

2017-10-01

Autoimmunity occurs in chronic obstructive pulmonary disease (COPD). We describe an antigen microarray for detecting serum autoantibodies (AAbs) to determine how IgM, as well as IgG, AAbs distinguish patients with COPD from controls with a history of smoking without COPD. All COPD patients' sera contained elevated levels of AAbs to some of 30 autoantigens. There were significant differences in the autoantigenic specificities of IgM AAbs compared to IgG AAbs in the COPD sera: for example, AAbs to histone and scl-70 were mainly IgG, whereas AAbs to CENP-B and La/ssB were mainly IgM; by contrast, IgM and IgG AAbs to collagen-V were equally prevalent. Thus, a combination of IgM and IgG AAbs specific for multiple autoantigens are detected in all cases of COPD at a level at which all non-COPD controls are negative for AAbs. This highlights the importance of different classes of AAbs to a range of autoantigens in COPD. Copyright © 2017 Elsevier Inc. All rights reserved.

Correlation between the Amount of Anti-D Antibodies and IgG Subclasses with Severity of Haemolytic Disease of Foetus and Newborn.

PubMed

Velkova, Emilija

2015-06-15

The aim of this study was to investigate the influence of subclasses to IgG anti-D on the intensity of hemolytic disease of fetus and newborn (HDFN) at 45 fetuses/newborns with symptoms of mild and severe HDFN in Republic of Macedonia. In retrospective and prospective studies, in a period of 10 years, from 2004 to 2014, there have been immunohemathology tests performed on 22 009 samples on serums of pregnant women. At 37.78% of the total number of tested patients, IgG1 and IgG3 was the reason for severe HDFN. At 17.77% of the total number of tested patients, which had only IgG1detected, was the reason for serious intensity of HDFN. The correlation of the titer to anti-D antibodies in the mother's serum and the intensity of HDFN were researched in 48 newborns. The titers between 1:8 and 1:32 resulted in 3 cases of HDFN with symptoms of severe disease and in 4 cases there were no signs of HDFN. At 12 women that had a titre between 1:32 and 1:512, five of the newborns developed severe HDFN, and seven had symptoms of mild and weak intensity form. In 3 cases the titer was higher than 512, and out of them one newborn had weak symptoms of HDFN, one developed severe HDFN and one ended with foetal death. Only in one case the titer reached a value higher than 1000, and it ended with a fetal death. The titers of the pregnant women serum those are lower than 32 and those higher than 1000 can well predict HDFN. The titers of anti-D antibodies between 64 and 512 have no exact predictive value. IgG1 and IgG3 subclasses of anti-D have no predictive value by themselves, and cannot foresee the outcome of HDFN. The research study results suggest that IgG1 and IgG3 should be included in a multi - parameter protocol for evaluation of the HDFN intensity. They can give a real assessment of the expected HDFN intensity in combination with the titer hight and the significance of the antibodies.

High CMV IgG antibody levels are associated to a lower CD4+ RESPONSE to antiretroviral therapy in HIV-infected women.

PubMed

Giuliano, Marina; Pirillo, Maria Franca; Liotta, Giuseppe; Andreotti, Mauro; Jere, Haswell; Sagno, Jean-Baptiste; Ciccacci, Fausto; Amici, Roberta; Marazzi, Maria Cristina; Vella, Stefano; Palombi, Leonardo; Mancinelli, Sandro

2017-11-01

Virtually all HIV-infected women in sub-Saharan Africa have evidence of Cytomegalovirus (CMV) infection and levels of specific anti-CMV IgG have been suggested to represent more intense reactivation of subclinical infection. Studies have also shown direct influence of CMV on lymphocytes. The aim of this study was to determine if levels of anti-CMV specific antibodies could impact on the immunological response to antiretroviral treatment (ART) in HIV-infected pregnant women. CMV-specific IgG were measured in HIV-infected pregnant women at 26 weeks of gestation (before ART initiation). Women received ART until 6 months postpartum or indefinitely according to local guidelines at the time of the study. Immunological and virological responses were assessed 6 months and 24 months after delivery. A total of 81 women were studied. At baseline high levels (above the median) of specific IgG were associated to a low CD4+ cell count (P<0.001), a high viral load (P=0.003), and to an older age (P=0.051). In a multivariate model adjusting for baseline CD4+ count, baseline viral load and age, the presence of low levels of CMV IgG was the only independent predictor of a a CD4+ count above 500/mm 3 24 months after delivery among women on continuous therapy. In this cohort, levels of CVM IgG had a significant influence on the immunological response to ART, adding information to the known impact of CMV infection in the HIV-positive population, and underlining the need of new strategies to contain the infection. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparison of in-house biotin-avidin tetanus IgG enzyme-linked-immunosorbent assay (ELISA) with gold standard in vivo mouse neutralization test for the detection of low level antibodies.

PubMed

Sonmez, Cemile; Coplu, Nilay; Gozalan, Aysegul; Akin, Lutfu; Esen, Berrin

2017-06-01

Detection of anti-tetanus antibody levels is necessary for both determination of the immune status of individuals and also for planning preventive measures. ELISA is the preferred test among in vitro tests however it can be affected by the cross reacting antibodies. A previously developed in-house ELISA test was found not reliable for the antibody levels ≤1.0IU/ml. A new method was developed to detect low antibody levels correctly. The aim of the present study was to compare the results of the newly developed in-house biotin-avidin tetanus IgG ELISA test with the in vivo mouse neutralization test, for the antibody levels ≤1.0IU/ml. A total of 54 serum samples with the antibody levels of three different levels, =0.01IU/ml, 0.01-0.1IU/ml, 0.1-1IU/ml, which were detected by in vivo mouse neutralization test were studied by the newly developed in-house biotin-avidin tetanus IgG ELISA test. Test was validated by using five different concentrations (0.01IU/ml, 0.06IU/ml, 0.2IU/ml, 0.5IU/ml, 1.0IU/ml). A statistically significant correlation (r 2 =0.9967 p=0,001) between in vivo mouse neutralization test and in-house biotin-avidin tetanus IgG ELISA test, was observed. For the tested concentrations intra-assay, inter-assay, accuracy, sensitivity, specificity and coefficients of variations were determined as ≤15%. In-house biotin-avidin tetanus IgG ELISA test can be an alternative method to in vivo mouse neutralization method for the detection of levels ≤1.0IU/ml. By using in-house biotin-avidin tetanus IgG ELISA test, individuals with non protective levels, will be reliably detected. Copyright © 2017. Published by Elsevier B.V.

ELISA-based assay of immunoglobulin G antibodies against mammalian cell entry 1A (Mce1A) protein: a novel diagnostic approach for leprosy.

PubMed

Lima, Filipe R; Takenami, Iukary; Cavalcanti, Maurílio Al; Riley, Lee W; Arruda, Sérgio

2017-12-01

Leprosy is a chronic infectious disease caused by the obligate intracellular bacillus Mycobacterium leprae. Because leprosy diagnosis is complex and requires professional expertise, new tools and methodologies are needed to detect cases in early stages and prevent transmission. The M. leprae genome contains mce1A, which encodes a putative mammalian cell entry protein (Mce1A). We hypothesised that the presence of Mce1A on the cell surface could be detected by the host's immune system. The aim of this study was to evaluate antibody responses against the Mce1A protein in leprosy patients, household contacts of patients, and the general population to present an addition tool for leprosy diagnosis. A cross-sectional study involving 89 volunteers [55 leprosy cases, 12 household contacts (HHC) and 22 endemic controls (EC)] was conducted at Couto Maia Hospital, in Salvador, Bahia (BA), Brazil. The median anti-Mce1A IgA was significantly higher in multibacillary (MB) and paucibacillary (PB) cases than in EC (p < 0.0001). A similar trend was observed in IgM levels, which were significantly higher in both MB (p < 0.0001) and PB (p = 0.0006) groups compared to in EC individuals. The greatest differences were observed for IgG class-specific antibodies against Mce1A. The median levels of MB and PB were significantly higher compared to both controls HHC and EC (MB or PB vs EC, MB vs HHC p < 0.0001; PB vs HHC, p = 0.0013). Among leprosy cases, IgG enzyme-linked immunosorbent assay sensitivity and specificity were 92.7% and 97.1%, respectively. IgG positivity was confirmed in 92.1% and 94.1% of MB and PB patients, respectively. This novel diagnostic approach presents an easy, non-invasive, and inexpensive method for leprosy screening, which may be applicable in endemic areas.

Impact of vegetarian diet on serum immunoglobulin levels in children.

PubMed

Gorczyca, Daiva; Prescha, Anna; Szeremeta, Karolina

2013-03-01

Nutrition plays an important role in immune response. We evaluated the effect of nutrient intake on serum immunoglobulin levels in vegetarian and omnivore children. Serum immunoglobulin levels and iron status were estimated in 22 vegetarian and 18 omnivore children. Seven-day food records were used to assess the diet. There were no significant differences in serum IgA, IgM, and IgG levels between groups of children. Serum immunoglobulin levels were lower in vegetarian children with iron deficiency in comparison with those without iron deficiency. In the vegetarians, IgG level correlated positively with energy, zinc, copper, and vitamin B(6) intake. In the omnivores, these correlations were stronger with IgM level. Despite negligible differences in serum immunoglobulin levels between vegetarian and omnivore children, the impact of several nutrient intakes on IgM and IgG levels differed between groups. Low iron status in vegetarian children can lead to decreased immunoglobulin levels.

[Analysis of Correlation between IgG Titer of Pregnant Women and Neonatal Hemolytic Complications of Different Blood Groups].

PubMed

Ye, Hai-Hui; Huang, Hong-Hai; Wang, Xiao-Lin; Pi, You-Jun

2017-10-01

To study the relationship between IgG titer of pregnant women and hemolytic disease of newborn(HDN) with different blood groups. Four hundred pregnant women, including pregnant women with type O blood, were selected from May 2014 to January 2015 in our hospital for inspection and a couple of different blood groups, the IgG titer of pregnant women were detected in the inspection process. According to neonatal HDN, newborns were divided into 2 groups: HDN group(85 cases) and non-HDN group(315 cases). The incidence of postpartum neonatal hemolytic disease was tracked and the correlation of IgG titers with HDN were systematically analyzed. In the production and inspection process, the IgG titer in pregnant women was divided into <1:64, 1:64, 1:128, 1:256 and greater than or equal to 1:512 five groups. the comparison of HDN incidence rate in 4 groups of IgG titer >64 and IgG titer <1:64 group showed that the prevalence of ABO hemolytic disease of newborn were 96.9%, 79.6%, 63, 7% and 28.8%, there was a certain correlation of pregnant women IgG titers with ABO hemolytic disease of the newborn, that is, with the increase of IgG titer, the incidence of hemolytic disease of newborns increased in certain degree (r=0.8832), the risk in 4 groups of neonatal HDN was higher than that in IgG titer <1:64 of IgG titer >64 HDN group. There is a certain corelation between prevalence of ABO-HDN and IgG titer of pregnant women. For these pregnant women, the control of the pregnant women IgG titer has a positive clinical significance to reduce the incidence of hemolytic disease of the newborn.

Prime-Boost Vaccination with Toxoplasma Lysate Antigen, but Not with a Mixture of Recombinant Protein Antigens, Leads to Reduction of Brain Cyst Formation in BALB/c Mice

PubMed Central

Wagner, Angelika; Schabussova, Irma; Ruttkowski, Bärbel; Peschke, Roman; Kur, Józef; Kundi, Michael; Joachim, Anja; Wiedermann, Ursula

2015-01-01

Introduction Infection with the ubiquitous parasite Toxoplasma gondii is a threat for immunocompromised patients and pregnant women and effective immune-prophylaxis is still lacking. Methods Here we tested a mixture of recombinant T. gondii antigens expressed in different developmental stages, i.e., SAG1, MAG1 and GRA7 (SMG), and a lysate derived from T. gondii tachyzoites (TLA) for prophylactic vaccination against cyst formation. Both vaccine formulations were applied systemically followed by an oral TLA-booster in BALB/c mice. Results Systemic priming with SMG and oral TLA-booster did not show significant induction of protective immune responses. In contrast, systemic priming and oral booster with TLA induced higher levels of Toxoplasma-specific IgG, IgG1 and IgG2a in sera as well as high levels of Toxoplasma-specific IgG1 in small intestines. Furthermore, high levels of Toxoplasma-specific Th1-, Th17- and Th2-associated cytokines were only detected in restimulated splenocytes of TLA-vaccinated mice. Importantly, in mice orally infected with T. gondii oocysts, only TLA-vaccination and booster reduced brain cysts. Furthermore, sera from these mice reduced tachyzoites invasion of Vero cells in vitro, indicating that antibodies may play a critical role for protection against Toxoplasma infection. Additionally, supernatants from splenocyte cultures of TLA-vaccinated mice containing high levels of IFN-γ lead to substantial production of nitric oxide (NO) after incubation with macrophages in vitro. Since NO is involved in the control of parasite growth, the high levels of IFN-γ induced by vaccination with TLA may contribute to the protection against T. gondii. Conclusion In conclusion, our data indicate that prime-boost approach with TLA, but not with the mixture of recombinant antigens SMG, induces effective humoral and cellular Toxoplasma-specific responses and leads to significant reduction of cerebral cysts, thereby presenting a viable strategy for further vaccine development against T. gondii infection. PMID:26010355

Mycobacterium tuberculosis thymidylate kinase antigen assays for designating incipient, high-risk latent M.tb infection.

PubMed

Wayengera, Misaki; Kateete, David P; Asiimwe, Benon; Joloba, Moses L

2018-03-16

Precise designation of high risk forms of latent Mycobacterium tuberculosis-M.tb infections (LTBI) is impossible. Delineation of high-risk LTBI can, however, allow for chemoprophylaxis and curtail majority cases of active tuberculosis (ATB). There is epidemiological evidence to support the view that LTBI in context of HIV-1 co-infection is high-risk for progression to ATB relative to LTBI among HIV-ve persons. We recently showed that assays of M.tb thymidylate kinase (TMKmt) antigen and host specific IgG can differentiate ATB from LTBI and or no TB (NTB, or healthy controls). In this study, we aimed to expose the differential levels of TMKmt Ag among HIV+ve co-infected LTBI relative to HIV-ve LTBI as a strategy to advance these assays for designating incipient LTBI. TMKmt host specific IgM and IgG detection Enzyme Immuno-Assays (EIA) were conducted on 40 TB exposed house-hold contacts (22 LTBI vs. 18 no TB (NTB) by QunatiFERON-TB GOLD®); and TMKmt Ag detection EIA done on 82 LTBI (46 HIV+ve vs 36 HIV-ve) and 9 NTB (American donors). Purified recombinant TMKmt protein was used as positive control for the Ag assays. IgM levels were found to be equally low across QuantiFERON-TB GOLD® prequalified NTB and TB exposed house-hold contacts. Higher TMKmt host specific IgG trends were found among TB house-hold contacts relative to NTB controls. TMKmt Ag levels among HIV+ve LTBI were 0.2676 ± 0.0197 (95% CI: 0.2279 to 0.3073) relative to 0.1069 ± 0.01628 (95% CI: 0.07385 to 0.14) for HIV-ve LTBI (supporting incipient nature of LTBI in context of HIV-1 co-infection). NTB had TMKmt Ag levels of 0.1013 ± 0.02505 (5% CI: 0.0421 to 0.1606) (intimating that some were indeed LTBI). TMKmt Ag levels represent a novel surrogate biomarker for high-risk LTBI, while host-specific IgG can be used to designate NTB from LTBI.

Infant HIV Type 1 gp120 Vaccination Elicits Robust and Durable Anti-V1V2 Immunoglobulin G Responses and Only Rare Envelope-Specific Immunoglobulin A Responses

PubMed Central

Fouda, Genevieve G.; Cunningham, Coleen K.; McFarland, Elizabeth J.; Borkowsky, William; Muresan, Petronella; Pollara, Justin; Song, Lin Ye; Liebl, Brooke E.; Whitaker, Kaylan; Shen, Xiaoying; Vandergrift, Nathan A.; Overman, R. Glenn; Yates, Nicole L.; Moody, M. Anthony; Fry, Carrie; Kim, Jerome H.; Michael, Nelson L.; Robb, Merlin; Pitisuttithum, Punnee; Kaewkungwal, Jaranit; Nitayaphan, Sorachai; Rerks-Ngarm, Supachai; Liao, Hua-Xin; Haynes, Barton F.; Montefiori, David C.; Ferrari, Guido; Tomaras, Georgia D.; Permar, Sallie R.

2015-01-01

Background Infant responses to vaccines can be impeded by maternal antibodies and immune system immaturity. It is therefore unclear whether human immunodeficiency virus type 1 (HIV-1) vaccination would elicit similar responses in adults and infants. Method HIV-1 Env–specific antibody responses were evaluated in 2 completed pediatric vaccine trials. In the Pediatric AIDS Clinical Trials Group (PACTG) 230 protocol, infants were vaccinated with 4 doses of Chiron rgp120 with MF59 (n = 48), VaxGen rgp120 with aluminum hydroxide (alum; n = 49), or placebo (n = 19) between 0 and 20 weeks of age. In PACTG 326, infants received 4 doses of ALVAC-HIV-1/AIDSVAX B/B with alum (n = 9) or placebo (n = 13) between 0 and 12 weeks of age. Results By 52 weeks of age, the majority of maternally acquired antibodies had waned and vaccine Env-specific immunoglobulin G (IgG) responses in vaccinees were higher than in placebo recipients. Chiron vaccine recipients had higher and more-durable IgG responses than VaxGen vaccine recipients or ALVAC/AIDSVAX vaccinees, with vaccine-elicited IgG responses still detectable in 56% of recipients at 2 years of age. Remarkably, at peak immunogenicity, the concentration of anti-V1V2 IgG, a response associated with a reduced risk of HIV-1 acquisition in the RV144 adult vaccine trial, was 22-fold higher in Chiron vaccine recipients, compared with RV144 vaccinees. Conclusion As exemplified by the Chiron vaccine regimen, vaccination of infants against HIV-1 can induce robust, durable Env-specific IgG responses, including anti-V1V2 IgG. PMID:25170104

Equine sperm-bound antisperm antibodies are associated with poor semen quality.

PubMed

Ferrer, M S; Miller, L M J

2018-06-01

Antisperm antibodies (ASAs) have been associated with infertility in stallions. The objectives of this study were to investigate the frequency of ASA-positive semen samples in satisfactory and non-satisfactory breeder stallions, the association between ASA binding and semen quality, and factors that may affect the diagnosis. Breeding soundness examinations were performed in 21 stallions and the percentage of IgG- and IgA-bound spermatozoa was evaluated using flow cytometry. Median IgG and IgA binding did not differ between the first and second ejaculates. The percentage of IgA-bound spermatozoa was higher in non-satisfactory (n = 10) than satisfactory breeder stallions (n = 11). However, IgG binding or frequency of IgG-positive ejaculates did not differ with stallion classification. The IgG-positive stallions had significantly lower total sperm motility, concentration and total numbers than IgG-negative stallions in the first ejaculate, and lower sperm concentration in the second ejaculate. The IgA-positive stallions had lower total sperm motility, normal spermatozoa and total numbers than IgA-negative stallions in the first ejaculate, and lower total sperm motility, normal spermatozoa and total numbers in the second ejaculate. While IgG binding did not differ with season, IgA binding was higher in the non-breeding season (n = 6 stallions) than the breeding season (n = 15 stallions) in the first ejaculate. Stallion age did not differ with ASA classification. In conclusion, IgG binding was highly prevalent in both groups of stallions, while IgA binding was higher and more prevalent in non-satisfactory breeders. Both isotypes were associated with poor semen quality. Season and sexual rest had an effect on IgA but not IgG binding. Copyright © 2018 Elsevier Inc. All rights reserved.

Effect of supranutritional maternal and colostral selenium supplementation on passive absorption of immunoglobulin G in selenium-replete dairy calves.

PubMed

Hall, Jean A; Bobe, Gerd; Vorachek, William R; Estill, Charles T; Mosher, Wayne D; Pirelli, Gene J; Gamroth, Mike

2014-07-01

Selenium (Se) is an essential micronutrient for ruminant animals affecting both performance and immune functions. Adding 3 mg of Se/L (in the form of Na selenite) to colostrum has been shown to improve IgG absorption in Se-deficient newborn dairy calves. The objective of our study was to determine the effect of supranutritional maternal and colostral Se supplementation on IgG status of Se-replete dairy calves. The study design was a 2 × 2 × 2 factorial design. During the last 8 wk before calving, dairy cows at a commercial dairy were fed either 0 (control cows) or 105 mg of Se-yeast once weekly (supranutritional Se-yeast-supplemented cows), in addition to Na selenite at 0.3 mg of Se/kg of DM in their ration. After birth, calves were fed pooled colostrum from control or supranutritional Se-yeast-supplemented cows to which 0 or 3 mg of Se/L (in the form of Na selenite) was added. Concentrations of whole-blood (WB) Se and serum Se measured at birth and at 48 h and 14 d of age, and serum IgG concentrations measured at 48 h and 14 and 60 d of age were determined. Calves born to Se-yeast-supplemented cows had higher WB-Se and serum-Se concentrations for the first 2 wk, and higher IgG absorption efficiency (62% at 48 h), resulting in higher serum-IgG concentrations (43% at 48 h and 65% at 14 d) and higher total serum-IgG content (50% at 48 h and 75% at 14 d), compared with calves born to control cows. Calves that received colostrum with added Na selenite had higher WB-Se concentrations for the first 2 wk, but only at 14 d of age were serum-Se concentrations, serum-IgG concentrations (53% higher), and total serum-IgG content (56% higher) higher, compared with calves that were fed colostrum without added Na selenite. Calves born to Se-yeast-supplemented cows that received colostrum from Se-yeast cows without added Na selenite had a higher IgG absorption efficiency compared with all other treatment groups. Our results support that feeding cows supranutritional Se-yeast supplement during the dry period or spiking colostrum with Na selenite both improve IgG status of Se-replete calves. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Seropositivity for the human heat shock protein (Hsp)60 accompanying seropositivity for Chlamydia trachomatis is less prevalent among tubal ectopic pregnancy cases than individuals with normal reproductive history.

PubMed

Ozyurek, Eser S; Karacan, Tolga; Ozdalgicoglu, Cenk; Yilmaz, Salih; Isik, Salman; San, Mevlide; Kaya, Erdal

2018-04-01

To investigate the role of anti-human heat shock protein 60 (hHsp60) antibody positivity in the pathogenesis of ectopic pregnancy, following Chlamydia trachomatis (CT) infection. In a case-control study, serological tests for anti-hHsp60 were performed in ectopic pregnancies (study group) and parturients with normal reproductive histories (control group). All participants in both groups were CT IgG(+). hHsp60 IgG(+) prevalences were compared between the two groups, by semiquantitative ELISA. Data were evaluated using nonparametric and parametric tests and multivariable regression. After an initial pilot study, two groups were formed: 63 ectopic gestations (study group) and 95 normal parturients (control group), all CT IgG(+). Blood samples from all cases were tested for anti-hHsp60 IgG. Age, gravidity, and practising contraception were higher in the control group, while a history of pelvic infections were more common in the study group. Hsp60 IgG(+) was found to be significantly higher in the control group (63/95, 66.3%) compared to study group (30/63, 47.6%). Regression analysis revealed anti-hHsp60 positivity was an independent factor delineating the two groups. Immunity to hHsp60 is less common in CT IgG(+) ectopic pregnancies than CT IgG(+) fertile subjects without a history of ectopic pregnancies. Hence, our findings suggest that hHsp60 seropositivity may decrease the probability of an ectopic gestation in subjects with previous CT infections. Copyright © 2018 Elsevier B.V. All rights reserved.

Expansion of blood IgG4+ B, TH2, and regulatory T cells in patients with IgG4-related disease.

PubMed

Heeringa, Jorn J; Karim, A Faiz; van Laar, Jan A M; Verdijk, Robert M; Paridaens, Dion; van Hagen, P Martin; van Zelm, Menno C

2018-05-01

IgG 4 -related disease (IgG 4 -RD) is a systemic fibroinflammatory condition affecting various organs and has a diverse clinical presentation. Fibrosis and accumulation of IgG 4 + plasma cells in tissue are hallmarks of the disease, and IgG 4 -RD is associated with increased IgG 4 serum levels. However, disease pathogenesis is still unclear, and these cellular and molecular parameters are neither sensitive nor specific for the diagnosis of IgG 4 -RD. Here we sought to develop a flow cytometric gating strategy to reliably identify blood IgG 4 + B cells to study their cellular and molecular characteristics and investigate their contribution in disease pathogenesis. Sixteen patients with histologically confirmed IgG 4 -RD, 11 patients with sarcoidosis, and 30 healthy subjects were included for 11-color flow cytometric analysis of peripheral blood for IgG 4 -expressing B cells and T H subsets. In addition, detailed analysis of activation markers and chemokine receptors was performed on IgG 4 -expressing B cells, and IgG 4 transcripts were analyzed for somatic hypermutations. Cellular and molecular analyses revealed increased numbers of blood IgG 4 + memory B cells in patients with IgG 4 -RD. These cells showed reduced expression of CD27 and CXCR5 and increased signs of antibody maturation. Furthermore, patients with IgG 4 -RD, but not patients with sarcoidosis, had increased numbers of circulating plasmablasts and CD21 low B cells, as well as T H 2 and regulatory T cells, indicating a common disease pathogenesis in patients with IgG 4 -RD. These results provide new insights into the dysregulated IgG 4 response in patients with IgG 4 -RD. A specific "peripheral lymphocyte signature" observed in patients with IgG 4 -RD, could support diagnosis and treatment monitoring. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

IgG Donor-Specific Anti-Human HLA Antibody Subclasses and Kidney Allograft Antibody-Mediated Injury.

PubMed

Lefaucheur, Carmen; Viglietti, Denis; Bentlejewski, Carol; Duong van Huyen, Jean-Paul; Vernerey, Dewi; Aubert, Olivier; Verine, Jérôme; Jouven, Xavier; Legendre, Christophe; Glotz, Denis; Loupy, Alexandre; Zeevi, Adriana

2016-01-01

Antibodies may have different pathogenicities according to IgG subclass. We investigated the association between IgG subclasses of circulating anti-human HLA antibodies and antibody-mediated kidney allograft injury. Among 635 consecutive kidney transplantations performed between 2008 and 2010, we enrolled 125 patients with donor-specific anti-human HLA antibodies (DSA) detected in the first year post-transplant. We assessed DSA characteristics, including specificity, HLA class specificity, mean fluorescence intensity (MFI), C1q-binding, and IgG subclass, and graft injury phenotype at the time of sera evaluation. Overall, 51 (40.8%) patients had acute antibody-mediated rejection (aABMR), 36 (28.8%) patients had subclinical ABMR (sABMR), and 38 (30.4%) patients were ABMR-free. The MFI of the immunodominant DSA (iDSA, the DSA with the highest MFI level) was 6724±464, and 41.6% of patients had iDSA showing C1q positivity. The distribution of iDSA IgG1-4 subclasses among the population was 75.2%, 44.0%, 28.0%, and 26.4%, respectively. An unsupervised principal component analysis integrating iDSA IgG subclasses revealed aABMR was mainly driven by IgG3 iDSA, whereas sABMR was driven by IgG4 iDSA. IgG3 iDSA was associated with a shorter time to rejection (P<0.001), increased microcirculation injury (P=0.002), and C4d capillary deposition (P<0.001). IgG4 iDSA was associated with later allograft injury with increased allograft glomerulopathy and interstitial fibrosis/tubular atrophy lesions (P<0.001 for all comparisons). Integrating iDSA HLA class specificity, MFI level, C1q-binding status, and IgG subclasses in a Cox survival model revealed IgG3 iDSA and C1q-binding iDSA were strongly and independently associated with allograft failure. These results suggest IgG iDSA subclasses identify distinct phenotypes of kidney allograft antibody-mediated injury. Copyright © 2016 by the American Society of Nephrology.

Serum antibody responses in pigs trickle-infected with Ascaris and Trichuris: Heritabilities and associations with parasitological findings.

PubMed

Kringel, Helene; Thamsborg, Stig Milan; Petersen, Heidi Huus; Göring, Harald Heinz Herbert; Skallerup, Per; Nejsum, Peter

2015-07-30

A humoral immune response following helminth infection in pigs is well documented. However, it has been difficult to confirm the existence of antibody mediated resistance against the large roundworm, Ascaris suum, and whipworm, Trichuris suis, in experimental settings by correlating worm burdens or egg excretion with specific antibody levels. We set out to investigate the association between worm load and T. suis and A. suum specific serum antibody levels (IgG1, IgG2 and IgA) against excretory-secretory products of adults and third stage larvae, respectively, measured at 0, 7 and 14 weeks p.i. in a trickle-infected F1-resource-population of crossbred pigs (n=195). Furthermore, we wanted to determine the heritability of these antibody isotypes during the course of infection. Most pigs remained infected with A. suum throughout the experiment while they expelled T. suis between 7 and 14 weeks post infection (p.i.). Parasite specific IgG1 and IgA were significantly (P<0.001) elevated after 7 and 14 weeks of infection, whereas parasite specific IgG2 levels only changed slightly at 14 weeks p.i.. However, the observed association between specific antibody isotype levels and faecal egg counts and macroscopic worm load was weak. The relative heritabilities of the different parasite specific isotypes were assessed and resulted in significant heritability estimates for parasite specific IgG1 and IgA. The highest heritabilities were found for A. suum specific IgG1 (h(2)=0.41 and 0.46 at 7 and 14 weeks p.i., respectively). Thus, the present study demonstrates that host genetic factors influence the IgG1 and IgA antibody isotype responses specific to two of the most common gastrointestinal nematodes of swine whereas specific antibody levels were poorly associated with egg excretion and the presence of macroscopic worms. Copyright © 2015. Published by Elsevier B.V.

Passive immunization of macaques with polyclonal anti-SHIV IgG against a heterologous tier 2 SHIV: outcome depends on IgG dose

PubMed Central

2014-01-01

Background A key goal for HIV-1 envelope immunogen design is the induction of cross-reactive neutralizing antibodies (nAbs). As AIDS vaccine recipients will not be exposed to strains exactly matching any immunogens due to multiple HIV-1 quasispecies circulating in the human population worldwide, heterologous SHIV challenges are essential for realistic vaccine efficacy testing in primates. We assessed whether polyclonal IgG, isolated from rhesus monkeys (RMs) with high-titer nAbs (termed SHIVIG), could protect RMs against the R5-tropic tier-2 SHIV-2873Nip, which was heterologous to the viruses or HIV-1 envelopes that had elicited SHIVIG. Results SHIVIG demonstrated binding to HIV Gag, Tat, and Env of different clades and competed with the broadly neutralizing antibodies b12, VRC01, 4E10, and 17b. SHIVIG neutralized tier 1 and tier 2 viruses, including SHIV-2873Nip. NK-cell depletion decreased the neutralizing activity of SHIVIG 20-fold in PBMC assays. Although SHIVIG neutralized SHIV-2873Nip in vitro, this polyclonal IgG preparation failed to prevent acquisition after repeated intrarectal low-dose virus challenges, but at a dose of 400 mg/kg, it significantly lowered peak viremia (P = 0.001). Unexpectedly, single-genome analysis revealed a higher number of transmitted variants at the low dose of 25 mg/kg, implying increased acquisition at low SHIVIG levels. In vitro, SHIVIG demonstrated complement-mediated Ab-dependent enhancement of infection (C’-ADE) at concentrations similar to those observed in plasmas of RMs treated with 25 mg/kg of SHIVIG. Conclusion Our primate model data suggest a dual role for polyclonal anti-HIV-1 Abs depending on plasma levels upon virus encounter. PMID:24444350

Comparative analysis of immune effects in mice model: Clonorchis sinensis cysteine protease generated from recombinant Escherichia coli and Bacillus subtilis spores.

PubMed

Wu, Zhanshuai; Tang, Zeli; Shang, Mei; Zhao, Lu; Zhou, Lina; Kong, Xiangzhan; Lin, Zhipeng; Sun, Hengchang; Chen, Tingjin; Xu, Jin; Li, Xuerong; Huang, Yan; Yu, Xinbing

2017-07-01

Clonorchiasis remains a nonnegligible public health problem in endemic areas. Cysteine protease of Clonorchis sinensis (CsCP) plays indispensable roles in the parasitic physiology and pathology, and has been exploited as a promising drug and vaccine candidate. In recent years, development of spore-based vaccines against multiple pathogens has attracted many investigators' interest. In previous studies, the recombinant Escherichia coli (BL21) and Bacillus subtilis spores expressing CsCP have been successfully constructed, respectively. In this study, the immune effects of CsCP protein purified from recombinant BL21 (rCsCP) and B. subtilis spores presenting CsCP (B.s-CsCP) in Balb/c mice model were conducted with comparative analysis. Levels of specific IgG, IgG1 and IgG2a were significantly increased in sera from both rCsCP and B.s-CsCP intraperitoneally immunized mice. Additionally, recombinant spores expressing abundant fusion CsCP (0.03125 pg/spore) could strongly enhance the immunogenicity of CsCP with significantly higher levels of IgG and isotypes. Compared with rCsCP alone, intraperitoneal administration of mice with spores expressing CsCP achieved a better effect of fighting against C. sinensis infection by slowing down the process of fibrosis. Our results demonstrated that a combination of Th1/Th2 immune responses could be elicited by rCsCP, while spores displaying CsCP prominently induced Th1-biased specific immune responses, and the complex cytokine network maybe mediates protective immune responses against C. sinensis. This work further confirmed that the usage of B. subtilis spores displaying CsCP is an effective way to against C. sinensis.

[Vaccination of rhesus monkeys with recombinant antigen fragments and protection from hepatitis E virus infection].

PubMed

Ma, Yan-bing; Xie, Tian-hong; Zhang, Guang-ming; Li, Chun-hong; Dai, Xie-Jie; Dai, Chang-bai; Sun, Mao-sheng; Lu, Jian; Bi, Sheng-li

2002-12-01

To observe anti-HEV IgG response to vaccination of recombinant antigen fragments and evaluate its protection from Hepatitis E Virus infection in rhesus monkeys (Macaca mulatta). Twelve monkeys were divided into three groups and immunized respectively with three different recombinant antigens: namely Ag1 (carboxyl terminal 431 amino acids of ORF2), Ag2 (128aa fragment at the carboxyl terminal of ORF2), and Ag3 (full length ORF3 ligated with two ORF2 fragments encoded by 6743-7126nt and 6287-6404nt). The monkeys were challenged intravenously with fecal suspension from experimentally infected rhesus monkeys, and the other three monkeys served as the placebo group for challenge with HEV. The dynamic changes of the levels of ALT and anti-HEV IgG were examined. Pathological changes of liver tissue were observed by light microscope. Excretion of virus was detected by RT-nPCR. Hepatic histopathology of two monkeys in the placebo group was consistent with acute viral hepatitis, and ALT was elevated 3-4 weeks after inoculated with virus, up to 10-20 times higher than normal level. The liver tissue of monkeys immunized with antigen kept normal, ALT in several monkeys elevated mildly, and anti-HEV IgG conversation occurred at 1-2 weeks after vaccination, with the titer reaching 1:12,800. The virus RNA could be detected by RT-nPCR from days 7 to 50 in monkeys of control group, and from days 7 to 21 in vaccinated monkeys after challenged with virus. The recombinant antigens could induce the production of anti-HEV IgG, which protected rhesus monkeys from acute Hepatitis symptoms related to HEV infection.

Passive immunization of macaques with polyclonal anti-SHIV IgG against a heterologous tier 2 SHIV: outcome depends on IgG dose.

PubMed

Sholukh, Anton M; Byrareddy, Siddappa N; Shanmuganathan, Vivekanandan; Hemashettar, Girish; Lakhashe, Samir K; Rasmussen, Robert A; Watkins, Jennifer D; Vyas, Hemant K; Thorat, Swati; Brandstoetter, Tania; Mukhtar, Muhammad M; Yoon, John K; Novembre, Francis J; Villinger, Francois; Landucci, Gary; Forthal, Donald N; Ratcliffe, Sarah; Tuero, Iskra; Robert-Guroff, Marjorie; Polonis, Victoria R; Bilska, Miroslawa; Montefiori, David C; Johnson, Welkin E; Ertl, Hildegund C; Ruprecht, Ruth M

2014-01-20

A key goal for HIV-1 envelope immunogen design is the induction of cross-reactive neutralizing antibodies (nAbs). As AIDS vaccine recipients will not be exposed to strains exactly matching any immunogens due to multiple HIV-1 quasispecies circulating in the human population worldwide, heterologous SHIV challenges are essential for realistic vaccine efficacy testing in primates. We assessed whether polyclonal IgG, isolated from rhesus monkeys (RMs) with high-titer nAbs (termed SHIVIG), could protect RMs against the R5-tropic tier-2 SHIV-2873Nip, which was heterologous to the viruses or HIV-1 envelopes that had elicited SHIVIG. SHIVIG demonstrated binding to HIV Gag, Tat, and Env of different clades and competed with the broadly neutralizing antibodies b12, VRC01, 4E10, and 17b. SHIVIG neutralized tier 1 and tier 2 viruses, including SHIV-2873Nip. NK-cell depletion decreased the neutralizing activity of SHIVIG 20-fold in PBMC assays. Although SHIVIG neutralized SHIV-2873Nip in vitro, this polyclonal IgG preparation failed to prevent acquisition after repeated intrarectal low-dose virus challenges, but at a dose of 400 mg/kg, it significantly lowered peak viremia (P = 0.001). Unexpectedly, single-genome analysis revealed a higher number of transmitted variants at the low dose of 25 mg/kg, implying increased acquisition at low SHIVIG levels. In vitro, SHIVIG demonstrated complement-mediated Ab-dependent enhancement of infection (C'-ADE) at concentrations similar to those observed in plasmas of RMs treated with 25 mg/kg of SHIVIG. Our primate model data suggest a dual role for polyclonal anti-HIV-1 Abs depending on plasma levels upon virus encounter.

Self-reactivities to the non-erythroid alpha spectrin correlate with cerebral malaria in Gabonese children.

PubMed

Guiyedi, Vincent; Chanseaud, Youri; Fesel, Constantin; Snounou, Georges; Rousselle, Jean-Claude; Lim, Pharat; Koko, Jean; Namane, Abdelkader; Cazenave, Pierre-André; Kombila, Maryvonne; Pied, Sylviane

2007-04-25

Hypergammaglobulinemia and polyclonal B-cell activation commonly occur in Plasmodium sp. infections. Some of the antibodies produced recognize self-components and are correlated with disease severity in P. falciparum malaria. However, it is not known whether some self-reactive antibodies produced during P. falciparum infection contribute to the events leading to cerebral malaria (CM). We show here a correlation between self-antibody responses to a human brain protein and high levels of circulating TNF alpha (TNFalpha), with the manifestation of CM in Gabonese children. To study the role of self-reactive antibodies associated to the development of P. falciparum cerebral malaria, we used a combination of quantitative immunoblotting and multivariate analysis to analyse correlation between the reactivity of circulating IgG with a human brain protein extract and TNFalpha concentrations in cohorts of uninfected controls (UI) and P. falciparum-infected Gabonese children developing uncomplicated malaria (UM), severe non-cerebral malaria (SNCM), or CM. The repertoire of brain antigens recognized by plasma IgGs was more diverse in infected than in UI individuals. Anti-brain reactivity was significantly higher in the CM group than in the UM and SNCM groups. IgG self-reactivity to brain antigens was also correlated with plasma IgG levels and age. We found that 90% of CM patients displayed reactivity to a high-molecular mass band containing the spectrin non-erythroid alpha chain. Reactivity with this band was correlated with high TNFalpha concentrations in CM patients. These results strongly suggest that an antibody response to brain antigens induced by P. falciparum infection may be associated with pathogenic mechanisms in patients developing CM.

Self-Reactivities to the Non-Erythroid Alpha Spectrin Correlate with Cerebral Malaria in Gabonese Children

PubMed Central

Fesel, Constantin; Snounou, Georges; Rousselle, Jean-Claude; Lim, Pharat; Koko, Jean; Namane, Abdelkader; Cazenave, Pierre-André; Kombila, Maryvonne; Pied, Sylviane

2007-01-01

Background Hypergammaglobulinemia and polyclonal B-cell activation commonly occur in Plasmodium sp. infections. Some of the antibodies produced recognize self-components and are correlated with disease severity in P. falciparum malaria. However, it is not known whether some self-reactive antibodies produced during P. falciparum infection contribute to the events leading to cerebral malaria (CM). We show here a correlation between self-antibody responses to a human brain protein and high levels of circulating TNF alpha (TNFα), with the manifestation of CM in Gabonese children. Methodology To study the role of self-reactive antibodies associated to the development of P. falciparum cerebral malaria, we used a combination of quantitative immunoblotting and multivariate analysis to analyse correlation between the reactivity of circulating IgG with a human brain protein extract and TNFα concentrations in cohorts of uninfected controls (UI) and P. falciparum-infected Gabonese children developing uncomplicated malaria (UM), severe non-cerebral malaria (SNCM), or CM. Results/Conclusion The repertoire of brain antigens recognized by plasma IgGs was more diverse in infected than in UI individuals. Anti-brain reactivity was significantly higher in the CM group than in the UM and SNCM groups. IgG self-reactivity to brain antigens was also correlated with plasma IgG levels and age. We found that 90% of CM patients displayed reactivity to a high-molecular mass band containing the spectrin non-erythroid alpha chain. Reactivity with this band was correlated with high TNFα concentrations in CM patients. These results strongly suggest that an antibody response to brain antigens induced by P. falciparum infection may be associated with pathogenic mechanisms in patients developing CM. PMID:17460756

Enterocolic lymphocytic phlebitis as a newly recognized manifestation of IgG4-related disease.

PubMed

Laco, Jan; Örhalmi, Július; Bártová, Jolana; Zimandlová, Dana

2015-04-01

Herein we present a case of a 65-year-old woman with enterocolic lymphocytic phlebitis (ELP) who presented with anemic syndrome and in whom severe stenosis of the right flexure of large bowel was detected. The microscopic examination revealed fibrosis of the submucosa and lymphoplasmacytic phlebitis of small veins and venules, whereas arteries were spared. There were 110 IgG4-positive and 160 IgG-positive plasma cells in 1 high-power field, respectively, with corresponding IgG4/IgG ratio of 0.69. The IgG4 serum level was 2.42 g/L. According to the currently proposed criteria, this ELP case is the first that may be diagnosed as definite IgG4-related disease (IgG4-RD). Although based on the sole case description, taken together with a recent review and a case report, we presume that a subset of ELPs is a manifestation of IgG4-RD. © The Author(s) 2014.

IgG4-related disease of the rectum

PubMed Central

Choi, Sung-Bong; Lim, Chul-Hyun; Cha, Myung-Guen

2016-01-01

IgG4-related disease is a relatively new disease entity characterized by elevated serum IgG4 levels and marked infiltration of IgG4-positive plasma cells in lesions. Organ enlargement or nodular lesions consisting of abundant infiltration of lymphocytes and IgG4-positive plasma cells and fibrosis are seen in various organs throughout. We encountered a patient with an inflammatory pseudotumor of the rectum, which was histopathologically confirmed to be an IgG4-related disease. The patient was a 28-year-old woman who had constipation for 3 months. The endoluminal ultrasonography showed a lesion that was heterogeneous and low echogenic in lower rectum. The result of colonoscopic biopsy findings was of chronic proctitis with lymphoid aggregates. For a confirmative diagnosis, excision was performed. Histopathological examination represented plasma cell infiltration and fibrosis. Immunohistochemistry revealed prominence of IgG4-positive plasma cells and confirmed the diagnosis of IgG4-related disease. The patient is currently under observation on low-dose oral prednisolone without relapse. PMID:27186575

Association of IgG co-deposition with serum levels of galactose-deficient IgA1 in pediatric IgA nephropathy

PubMed Central

Eison, T. Matthew; Hastings, M. Colleen; Moldoveanu, Zina; Sanders, John T.; Gaber, Lillian; Walker, Patrick D.; Lau, Keith K; Julian, Bruce A.; Novak, Jan; Wyatt, Robert J.

2012-01-01

Objective: To determine whether the absence of mesangial IgG deposits is associated with the absence of elevated blood levels of galactose-deficient IgA1 (Gd-IgA1) in pediatric patients with IgA nephropathy (IgAN). Design and methods: Serum Gd-IgA1 levels were determined by ELISA using an N-acetylgalactosamine-specific lectin from Helix aspersa. Levels of Gd-IgA1 above the 90th percentile for healthy pediatric controls were considered to be elevated. Renal biopsy samples were examined by immunofluorescence for presence and intensity of staining for IgA, IgG, IgM, C3 and C1q and by light microscopy for histological changes. Findings were graded by a single pathologist (L. Gaber) at UTHSC until 2007 and by NephropathTM (Little Rock, AR, USA) thereafter. Staining for the mesangial deposits was considered negative when intensity was trace or less, and positive at greater intensity. Fisher’s exact-test was used to determine significance of 2 × 2 tables. Results: Serum samples were obtained from 30 patients with IgAN diagnosed before age 18 years. Male : female ratio was 2.3 : 1. Twenty were Caucasian and 10 were African-American. Blood was obtained within 3 months of biopsy (incident cases) for 12, while 18 provided blood > 3 months after biopsy (prevalent cases). Serum Gd-IgA1 level was elevated in 23 (77%) of cases and 20 (67%) had a biopsy positive for IgG. Of those 20 patients, 18 (90%) had an elevated serum Gd-IgA1 level, whereas 5 (50%) of patients with biopsies without IgG had a normal serum Gd-IgA1 level (p = 0.026). Summary: In this small study we found a weak association between the absence of IgG in the biopsy and normal serum Gd-IgA1 level. PMID:23006340

Association between bovine casein antibody and new onset schizophrenia among US military personnel.

PubMed

Niebuhr, David W; Li, Yuanzhang; Cowan, David N; Weber, Natalya S; Fisher, Jared A; Ford, Glen M; Yolken, Robert

2011-05-01

Schizophrenia is a pervasive neuropsychiatric disorder of uncertain etiology. Multiple studies have documented immune activation in individuals with schizophrenia. One antigen capable of inducing a prolonged immune response is bovine casein derived from ingested milk products. Increased levels of casein antibodies have been found in individuals with schizophrenia after diagnosis. This study was directed at determining the potential association between schizophrenia and pre-illness onset levels of immunoglobulin G (IgG) antibodies to bovine casein. Parallel analyses for casein antibody levels with bipolar disorder were included as comparison. Cases were service members who received medical discharges from the military with a schizophrenia diagnosis from 1992 to 2005. Serum specimens were selected for 855 cases and 1165 matched healthy controls. IgG antibodies to bovine whole-casein were measured by solid phase enzyme-linked immunosorbent assays (ELISAs). Hazard ratios (HR) were calculated to examine the associations of casein IgG level with risk of schizophrenia by time to diagnosis and by subjects' initial level. Increasing casein IgG antibody levels among those with a high initial level, drawn before diagnosis, was associated with an 18% increase in the hazard risk of schizophrenia per unit increase (value of low-positive standard) in IgG antibody levels (HR=1.18; 95% CI 1.04, 1.34). This is the first report to identify an association between the risk of schizophrenia and elevated antibodies to bovine casein prior to disease onset. Additional research is required to elucidate the complex genetic environmental interactions involved in the pathogenesis of schizophrenia and to identify potentially modifiable risk factors. Published by Elsevier B.V.

Community knowledge, health beliefs, practices and experiences related to dengue fever and its association with IgG seropositivity.

PubMed

Wong, Li Ping; AbuBakar, Sazaly; Chinna, Karuthan

2014-05-01

Demographic, economic and behavioural factors are central features underpinning the successful management and biological control of dengue. This study aimed to examine these factors and their association with the seroprevalence of this disease. We conducted a cross-sectional telephone survey of households in a 3 km radius of the schools where we had conducted serological tests on the student population in a previous study. Households were surveyed about their socio-demographics, knowledge, practices, and Health Belief Model (HBM) constructs. The results were then associated with the prevalence rate of dengue in the community, as marked by IgG seropositivity of the students who attended school there. A total of 1,400 complete responses were obtained. The community's IgG seropositivity was significantly positively associated with high household monthly income, high-rise residential building type, high surrounding vegetation density, rural locality, high perceived severity and susceptibility, perceived barriers to prevention, knowing that a neighbour has dengue, frequent fogging and a higher level of knowledge about dengue. In the multivariate analyses, three major correlates of the presence of IgG seropositivity in the community: (1) high-rise residential apartment house type or condominium buildings; (2) the main construct of the HBM, perceived severity and susceptibility; and (3) the additional constructs of the HBM, lack of preventive measures from the community level and having a neighbour with dengue as a cue to action. Weak correlations were found between self-practices to prevent dengue and the level of dengue seropositivity in the community, and between HBM constructs and knowledge (r = 0.09). The residential environment factor and the constructs of the HBM are useful and important elements in developing interventions to prevent and control dengue. The study also sheds light on the importance of the need for approaches that ensure the translation of knowledge into practice.

Canine leishmaniasis: Genome-wide analysis and antibody response to Lutzomyia longipalpis saliva.

PubMed

Batista, Luís F S; Utsunomiya, Yuri T; Silva, Thaís B F; Carneiro, Mariana M; Paiva, Joyr S F; Silva, Rafaela B; Tomokane, Thaíse Y; Rossi, Claudio N; Pacheco, Acácio D; Torrecilha, Rafaela B P; Silveira, Fernando T; Marcondes, Mary; Nunes, Cáris M; Laurenti, Márcia D

2018-01-01

The anti-inflammatory properties of sand fly saliva favor the establishment of the Leishmania infantum infection. In contrast, an antibody response against Lutzomyia longipalpis saliva is often associated with a protective cell-mediated response against canine visceral leishmaniasis. Genetic studies may demonstrate to what extent the ability to secrete anti-saliva antibodies depends on genetic or environmental factors. However, the genetic basis of canine antibody response against sand fly saliva has not been assessed. The aim of this study was to identify chromosomal regions associated with the anti-Lu. longipalpis salivary IgG response in 189 dogs resident in endemic areas in order to provide information for prophylactic strategies. Dogs were classified into five groups based on serological and parasitological diagnosis and clinical evaluation. Anti-salivary gland homogenate (SGH) IgG levels were assessed by Enzyme-Linked Immunosorbent Assay (ELISA). Genomic DNA was isolated from blood samples and genotyped using a SNP chip with 173,662 single nucleotide polymorphism (SNP) markers. The following linear regression model was fitted: IgG level = mean + origin + sex + age + use of a repellent collar, and the residuals were assumed as pseudo-phenotypes for the association test between phenotypes and genotypes (GWA). A component of variance model that takes into account polygenic and sample structure effects (EMMAX) was employed for GWA. Phenotypic findings indicated that anti-SGH IgG levels remained higher in exposed and subclinically infected dogs than in severely diseased dogs even in regression model residuals. Five associated markers were identified on chromosomes 2, 20 and 31. The mapped genes included CD180 (RP105) and MITF related to the rapid activation of B lymphocytes and differentiation into antibody-secreting plasma cells. The findings pointed to chromosomal segments useful for functional confirmation studies and a search for adjuvant molecules of the anti-saliva response.

Maternal Helminth Infection Is Associated With Higher Infant Immunoglobulin A Titers to Antigen in Orally Administered Vaccines

PubMed Central

Clark, Carolyn E.; Fay, Michael P.; Chico, Martha E.; Sandoval, Carlos A.; Vaca, Maritza G.; Boyd, Alexis; Cooper, Philip J.; Nutman, Thomas B.

2016-01-01

Background. Many studies have documented lower vaccine efficacy among children in low-income countries, compared with their counterparts in high-income countries. This disparity is especially apparent with respect to oral vaccines such as rotavirus and oral polio vaccines. One potential contributing factor is the presence of maternal antenatal helminth infections, which can modulate the infant's developing immune system. Methods. Using a multiplex immunoassay, we tested plasma immunoglobulin A (IgA) or immunoglobulin G (IgG) levels specific for antigens in 9 routinely administered childhood vaccines among 1639 children aged approximately 13 months enrolled in the ECUAVIDA (Ecuador Life) birth cohort study in Ecuador. We compared vaccine responses in 712 children of mothers who tested positive for helminth infections in the last trimester of pregnancy to responses in 927 children of mothers without helminth infection. Results. Plasma IgA levels specific for antigens in rotavirus vaccine and oral polio vaccine containing poliovirus serotypes 1 and 3 were all significantly higher in children of helminth-infected mothers, compared with children of uninfected mothers. Plasma IgG levels specific for diphtheria, tetanus, pertussis, measles, rubella, and Haemophilus influenzae type b vaccine antigens were comparable between the 2 groups. Conclusions. Antenatal maternal helminth infections were not associated with reduced antibody responses to infant vaccines, but rather with modestly increased IgA responses to oral vaccines. PMID:26908751

Blood biomarker for Parkinson disease: peptoids

PubMed Central

Yazdani, Umar; Zaman, Sayed; Hynan, Linda S; Brown, L Steven; Dewey, Richard B; Karp, David; German, Dwight C

2016-01-01

Parkinson disease (PD) is the second most common neurodegenerative disease. Because dopaminergic neuronal loss begins years before motor symptoms appear, a biomarker for the early identification of the disease is critical for the study of putative neuroprotective therapies. Brain imaging of the nigrostriatal dopamine system has been used as a biomarker for early disease along with cerebrospinal fluid analysis of α-synuclein, but a less costly and relatively non-invasive biomarker would be optimal. We sought to identify an antibody biomarker in the blood of PD patients using a combinatorial peptoid library approach. We examined serum samples from 75 PD patients, 25 de novo PD patients, and 104 normal control subjects in the NINDS Parkinson’s Disease Biomarker Program. We identified a peptoid, PD2, which binds significantly higher levels of IgG3 antibody in PD versus control subjects (P<0.0001) and is 68% accurate in identifying PD. The PD2 peptoid is 84% accurate in identifying de novo PD. Also, IgG3 levels are significantly higher in PD versus control serum (P<0.001). Finally, PD2 levels are positively correlated with the United Parkinson’s Disease Rating Scale score (r=0.457, P<0001), a marker of disease severity. The PD2 peptoid may be useful for the early-stage identification of PD, and serve as an indicator of disease severity. Additional studies are needed to validate this PD biomarker. PMID:27812535

Clinical outcome of calves with failure of passive transfer as diagnosed by a commercially available IgG quick test kit

PubMed Central

Stilwell, George; Carvalho, Rita C.

2011-01-01

The efficacy of an IgG quick test in detecting calves with failure of passive transfer was assessed. The test was carried out on 97 male calves, 38% of which were negative (IgG < 10 mg/mL). Morbidity and mortality due to infectious diseases were significantly higher in the negative group showing that the quick test is useful in identifying calves more susceptible to infectious disease. PMID:22043074

Neuron-derived IgG protects neurons from complement-dependent cytotoxicity.

PubMed

Zhang, Jie; Niu, Na; Li, Bingjie; McNutt, Michael A

2013-12-01

Passive immunity of the nervous system has traditionally been thought to be predominantly due to the blood-brain barrier. This concept must now be revisited based on the existence of neuron-derived IgG. The conventional concept is that IgG is produced solely by mature B lymphocytes, but it has now been found to be synthesized by murine and human neurons. However, the function of this endogenous IgG is poorly understood. In this study, we confirm IgG production by rat cortical neurons at the protein and mRNA levels, with 69.0 ± 5.8% of cortical neurons IgG-positive. Injury to primary-culture neurons was induced by complement leading to increases in IgG production. Blockage of neuron-derived IgG resulted in more neuronal death and early apoptosis in the presence of complement. In addition, FcγRI was found in microglia and astrocytes. Expression of FcγR I in microglia was increased by exposure to neuron-derived IgG. Release of NO from microglia triggered by complement was attenuated by neuron-derived IgG, and this attenuation could be reversed by IgG neutralization. These data demonstrate that neuron-derived IgG is protective of neurons against injury induced by complement and microglial activation. IgG appears to play an important role in maintaining the stability of the nervous system.

Amylolytic activity of IgM and IgG antibodies from patients with multiple sclerosis.

PubMed

Saveliev, Andrew N; Ivanen, Dina R; Kulminskaya, Anna A; Ershova, Nadezhda A; Kanyshkova, Tat'yana G; Buneva, Valentina N; Mogelnitskii, Alexander S; Doronin, Boris M; Favorova, Olga O; Nevinsky, Georgy A; Neustroev, Kirill N

2003-05-01

IgG and IgM antibodies from the sera of patients with multiple sclerosis (MS) were found to possess amylolytic activity hydrolyzing alpha-(1-->4)-glucosyl linkages of maltooligosaccharides, glycogen, and several artificial substrates. Individual IgM fractions isolated from 54 analyzed patients with the clinically definite diagnoses of MS had approximately three orders of magnitude higher specific amylolytic activity than that for healthy donors, whereas IgG from only a few patients had high amylolytic activity. Strict criteria were used to prove that the amylolytic activity of IgMs and IgGs is their intrinsic property and is not due to any enzyme contamination. Fab fragments produced from IgM and IgG fractions of the MS patients displayed the same amylolytic activity. IgMs from various patients demonstrated different modes of action in hydrolyzing maltooligosaccharides.

Hybrid kappa\\lambda antibody is a new serological marker to diagnose autoimmune pancreatitis and differentiate it from pancreatic cancer.

PubMed

Hao, Mingju; Li, Wenli; Yi, Lang; Yu, Songlin; Fan, Gaowei; Lu, Tian; Yang, Xin; Wang, Guojing; Zhang, Dong; Ding, Jiansheng; Zhang, Kuo; Zhang, Rui; Lin, Guigao; Han, Yanxi; Wang, Lunan; Li, Jinming

2016-06-08

The only generally accepted serological marker currently used for the diagnosis of autoimmune pancreatitis (AIP) is IgG4. Our aim was mainly to determine whether hybrid κ\\λ antibody can help to diagnose AIP and to differentiate it from pancreatic cancer. We established an enzyme-linked immunosorbent assay (ELISA) system to measure the levels of hybrid κ\\λ antibodies in human sera. Sera were obtained from 338 patients, including 61 with AIP, 74 with pancreatic cancer, 50 with acute pancreatitis, 40 with ordinary chronic pancreatitis, 15 with miscellaneous pancreatic diseases, and 98 with normal pancreas. Our study showed levels of hybrid κ\\λ antibodies in the AIP group were significantly higher than in the non-AIP group (P < 0.001). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the diagnosis of AIP were 80.3%, 91%, 66.2% and 95.5% respectively. Furthermore, the combined measurement of serum hybrid κ\\λ antibody and IgG4 tended to increase the sensitivity although the difference was not statistically significant (90.2% vs. 78.7%, P = 0.08), compared to measurement of IgG4 alone. Our findings suggest that hybrid κ\\λ antibody could be a new serological marker to diagnose AIP and differentiate it from pancreatic cancer.

Immune parameters to p67C antigen adjuvanted with ISA206VG correlate with protection against East Coast fever.

PubMed

Lacasta, Anna; Mwalimu, Stephen; Kibwana, Elisabeth; Saya, Rosemary; Awino, Elias; Njoroge, Thomas; Poole, Jane; Ndiwa, Nicholas; Pelle, Roger; Nene, Vishvanath; Steinaa, Lucilla

2018-03-07

East Coast fever (ECF) is a lymphoproliferative disease caused by the tick-transmitted protozoan parasite Theileria parva. ECF is one of the most serious cattle tick-borne diseases in Sub-Saharan Africa. We have previously demonstrated that three doses of the C-terminal part of the sporozoite protein p67 (p67C) adjuvanted with ISA206VG confers partial protection against ECF at a herd level. We have tested the efficacy of two doses of this experimental vaccine, as reducing the vaccination regimen would facilitate its deployment in the field. We reconfirm that three antigen doses gave a significant level of protection to severe disease (46%, ECF score < 6) when compared with the control group, while two doses did not (23%). Animals receiving three doses of p67C developed higher antibody titers and CD4 + T-cell proliferation indices, than those which received two doses. A new panel of immune parameters were tested in order to identify factors correlating with protection: CD4 + proliferation index, total IgG, IgG1, IgG2 and IgM half maximal titers and neutralization capacity of the sera with and without complement. We show that some of the cellular and humoral immune responses provide preliminary correlates of protection. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Hyaluronidase and hyaluronan in insect venom allergy.

PubMed

King, Te Piao; Wittkowski, Knut M

2011-01-01

Insect venoms contain an allergen hyaluronidase that catalyzes the hydrolysis of hyaluronan (HA), a polymer of disaccharide GlcUA-GlcNAc in skin. HAs depending on their size have variable function in inflammation and immunity. This paper reports on whether hyaluronidase, HA polymers and oligomers can promote antibody response in mice. HA oligomers (8- to 50-mer; 3-20 kDa) were obtained by bee venom hyaluronidase digestion of HA polymers (750- to 5,000-mer; 300-2,000 kDa). Antibody responses in mice were compared following 3 biweekly subcutaneous injection of ovalbumin (OVA) with or without test adjuvant. OVA-specific IgG1 levels were approximately 2 times higher in BALB/c and C3H/HeJ mice receiving OVA and HA oligomer or polymer than those treated with OVA alone, and no increase in total IgE level was observed. In C57Bl/6 mice, observed increases in IgG1 and IgE were 3.5- and 1.7-fold, respectively, for the oligomer and 16- and 5-fold (p < 0.05), respectively, for the polymer. Hyaluronidase by its action on HA in skin can function indirectly as adjuvant to promote IgE and IgG1 response in mice. Insect venoms also have cytolytic peptides and phospholipases with inflammatory roles. These activities found in mice may contribute to venom allergenicity in susceptible people. Copyright © 2011 S. Karger AG, Basel.

Human IgG1 Responses to Surface Localised Schistosoma mansoni Ly6 Family Members Drop following Praziquantel Treatment.

PubMed

Chalmers, Iain W; Fitzsimmons, Colin M; Brown, Martha; Pierrot, Christine; Jones, Frances M; Wawrzyniak, Jakub M; Fernandez-Fuentes, Narcis; Tukahebwa, Edridah M; Dunne, David W; Khalife, Jamal; Hoffmann, Karl F

2015-01-01

The heptalaminate-covered, syncytial tegument is an important anatomical adaptation that enables schistosome parasites to maintain long-term, intravascular residence in definitive hosts. Investigation of the proteins present in this surface layer and the immune responses elicited by them during infection is crucial to our understanding of host/parasite interactions. Recent studies have revealed a number of novel tegumental surface proteins including three (SmCD59a, SmCD59b and Sm29) containing uPAR/Ly6 domains (renamed SmLy6A SmLy6B and SmLy6D in this study). While vaccination with SmLy6A (SmCD59a) and SmLy6D (Sm29) induces protective immunity in experimental models, human immunoglobulin responses to representative SmLy6 family members have yet to be thoroughly explored. Using a PSI-BLAST-based search, we present a comprehensive reanalysis of the Schistosoma mansoni Ly6 family (SmLy6A-K). Our examination extends the number of members to eleven (including three novel proteins) and provides strong evidence that the previously identified vaccine candidate Sm29 (renamed SmLy6D) is a unique double uPAR/Ly6 domain-containing representative. Presence of canonical cysteine residues, signal peptides and GPI-anchor sites strongly suggest that all SmLy6 proteins are cell surface-bound. To provide evidence that SmLy6 members are immunogenic in human populations, we report IgG1 (as well as IgG4 and IgE) responses against two surface-bound representatives (SmLy6A and SmLy6B) within a cohort of S. mansoni-infected Ugandan males before and after praziquantel treatment. While pre-treatment IgG1 prevalence for SmLy6A and SmLy6B differs amongst the studied population (7.4% and 25.3% of the cohort, respectively), these values are both higher than IgG1 prevalence (2.7%) for a sub-surface tegumental antigen, SmTAL1. Further, post-treatment IgG1 levels against surface-associated SmLy6A and SmLy6B significantly drop (p = 0.020 and p < 0.001, respectively) when compared to rising IgG1 levels against sub-surface SmTAL1. Collectively, these results expand the number of SmLy6 proteins found within S. mansoni and specifically demonstrate that surface-associated SmLy6A and SmLy6B elicit immunological responses during infection in endemic communities.

Determination of soluble immunoglobulin G in bovine colostrum products by Protein G affinity chromatography-turbidity correction and method validation.

PubMed

Holland, Patrick T; Cargill, Anne; Selwood, Andrew I; Arnold, Kate; Krammer, Jacqueline L; Pearce, Kevin N

2011-05-25

Immunoglobulin-containing food products and nutraceuticals such as bovine colostrum are of interest to consumers as they may provide health benefits. Commercial scale colostrum products are valued for their immunoglobulin G (IgG) content and therefore require accurate analysis. One of the most commonly used methods for determining total soluble IgG in colostrum products is based on affinity chromatography using a Protein G column and UV detection. This paper documents improvements to the accuracy of the Protein G analysis of IgG in colostrum products, especially those containing aggregated forms of IgG. Capillary electrophoresis-sodium dodecyl sulfate (CE-SDS) analysis confirmed that aggregated IgG measured by Protein G does not contain significant amounts of casein or other milk proteins. Size exclusion chromatography identified the content of soluble IgG as mainly monomeric IgG and aggregated material MW > 450 kDa with small amounts of dimer and trimer. The turbidity of the eluting IgG, mainly associated with aggregated IgG, had a significant effect on the quantitative results. Practical techniques were developed to correct affinity LC data for turbidity on an accurate, consistent, and efficient basis. The method was validated in two laboratories using a variety of colostrum powders. Precision for IgG was 2-3% (RSD(r)) and 3-12% (RSD(R)). Recovery was 100.2 ± 2.4% (mean ± RSD, n = 10). Greater amounts of aggregated IgG were solubilized by a higher solution:sample ratio and extended times of mixing or sonication, especially for freeze-dried material. It is concluded that the method without acid precipitation and with turbidity correction provides accurate, precise, and robust data for total soluble IgG and is suitable for product specification and quality control of colostrum products.

Sensitivity and specificity of single IgA and IgG antibody concentrations for early diagnosis of pertussis in adults: an evaluation for outbreak management in public health practice

PubMed Central

Mertens, Paul LJM; Stals, Frans S; Steyerberg, Ewout W; Richardus, Jan H

2007-01-01

Background An accurate, practical laboratory test is needed to confirm clinical diagnosis of pertussis in adults during the first 3 symptomatic weeks, when treatment is effective and transmission can be interrupted. Methods The sensitivity and specificity of single IgA and IgG levels were assessed in a cohort study of a pertussis epidemic in 99 adults in a closed community. Sensitivities were assessed in the sera of 46 laboratory confirmed clinical pertussis cases during the first 3 weeks. Specificities were calculated in sera of 35 asymptomatic controls without clinical symptoms or laboratory confirmed infections from the same community (internal controls). We compared these specificities with the specificities of single IgA and IgG levels in 4275 external controls from a cross-section of the general Dutch population aged 21–79 years who had not coughed for more than 2 weeks in the past year, and without pertussis diagnoses. The study was done in the Netherlands when whole-cell pertussis vaccine was used in the national vaccination programme. Results Levels of 24 U/ml for IgA and 27 U/ml for IgG gave sensitivities of 100% and 75%, respectively, in the first 2 weeks, 100% in the third week, and 97% after the fourth week. The levels were reached within 2 days after onset of increase, and remained above these levels for roughly 7.2 and 5.1 months, respectively. Specificity was 82% for IgA and 89% for IgG in the internal controls and 90% in the external controls, respectively. Conclusion We suggest levels of 24 U/ml for IgA level and 27 U/ml (= 27 International Units (IU)/ml) for IgG as sensitive, specific, and practical for laboratory confirmation of clinical pertussis in adults in the first 3 weeks of outbreak management. PMID:17553132

Timing of an Adolescent Booster after Single Primary Meningococcal Serogroup C Conjugate Immunization at Young Age; An Intervention Study among Dutch Teenagers

PubMed Central

Stoof, Susanne P.; van der Klis, Fiona R. M.; van Rooijen, Debbie M.; Knol, Mirjam J.; Sanders, Elisabeth A. M.; Berbers, Guy A. M.

2014-01-01

Background Meningococcal serogroup C (MenC) specific antibody levels decline rapidly after a single primary MenC conjugate (MenCC) vaccination in preschool children. A second MenCC vaccination during (pre)adolescence might attain longer lasting individual and herd protection. We aimed to establish an appropriate age for a (pre)adolescent MenCC booster vaccination. Methods A phase-IV trial with healthy 10-year-olds (n = 91), 12-year-olds (n = 91) and 15-year-olds (n = 86) who were primed with a MenCC vaccine nine years earlier. All participants received a booster vaccination with the same vaccine. Serum bactericidal antibody assay titers (SBA, using baby rabbit complement), MenC-polysaccharide (MenC-PS) specific IgG, IgG subclass and avidity and tetanus-specific IgG levels were measured prior to (T0) and 1 month (T1) and 1 year (T2) after the booster. An SBA titer ≥8 was the correlate of protection. Results 258 (96.3%) participants completed all three study visits. At T0, 19% of the 10-year-olds still had an SBA titer ≥8, compared to 34% of the 12-year-olds (P = 0.057) and 45% of the 15-year-olds (P<0.001). All participants developed high SBA titers (GMTs>30,000 in all age groups) and MenC-PS specific IgG levels at T1. IgG levels mainly consisted of IgG1, but the contribution of IgG2 increased with age. At T2, 100% of participants still had an SBA titer ≥8, but the 15-year-olds showed the highest protective antibody levels and the lowest decay. Conclusion Nine years after primary MenCC vaccination adolescents develop high protective antibody levels in response to a booster and are still sufficiently protected one year later. Our results suggest that persistence of individual - and herd - protection increases with the age at which an adolescent booster is administered. Trial Registration EU Clinical Trials Database 2011-000375-13 Dutch Trial Register NTR3521 PMID:24963638

Enhanced HIV-1 neutralization by a CD4-VH3-IgG1 fusion protein

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meyuhas, Ronit; Noy, Hava; Fishman, Sigal

2009-08-21

HIV-1 gp120 is an alleged B cell superantigen, binding certain VH3+ human antibodies. We reasoned that a CD4-VH3 fusion protein could possess higher affinity for gp120 and improved HIV-1 inhibitory capacity. To test this we produced several human IgG1 immunoligands harboring VH3. Unlike VH3-IgG1 or VH3-CD4-IgG1, CD4-VH3-IgG1 bound gp120 considerably stronger than CD4-IgG1. CD4-VH3-IgG1 exhibited {approx}1.5-2.5-fold increase in neutralization of two T-cell laboratory-adapted strains when compared to CD4-IgG1. CD4-VH3-IgG1 improved neutralization of 7/10 clade B primary isolates or pseudoviruses, exceeding 20-fold for JR-FL and 13-fold for Ba-L. It enhanced neutralization of 4/8 clade C viruses, and had negligible effect onmore » 1/4 clade A pseudoviruses. We attribute this improvement to possible pairing of VH3 with CD4 D1 and stabilization of an Ig Fv-like structure, rather than to superantigen interactions. These novel findings support the current notion that CD4 fusion proteins can act as better HIV-1 entry inhibitors with potential clinical implications.« less

Enzyme immunoassays for IgG and IgM antibodies to Toxoplasma gondii based on enhanced chemiluminescence.

PubMed Central

Crouch, C F

1995-01-01

AIMS--To evaluate the clinical performance of enzyme immunoassays for IgG and IgM antibodies to Toxoplasma gondii based on enhanced chemiluminescence. METHODS--Classification of routine clinical samples from the originating laboratories was compared with that obtained using the chemiluminescence based assays. Resolution of discordant results was achieved by testing in alternative enzyme immunoassays (IgM) or by an independent laboratory using the dye test (IgG). RESULTS--Compared with resolved data, the IgM assay was found to be highly specific (100%) with a cut off selected to give optimal performance with respect to both the early detection of specific IgM and the detection of persistent levels of specific IgM (sensitivity 98%). Compared with resolved data, the IgG assay was shown to have a sensitivity and a specificity of 99.4%. CONCLUSIONS--The Amerlite Toxo IgM assay possesses high levels of sensitivity and specificity. Assay interference due to rheumatoid factor like substances is not a problem. The Amerlite Toxo IgG assay possesses good sensitivity and specificity, but is less sensitive for the detection of seroconversion than methods detecting both IgG and IgM. PMID:7560174

Epstein-Barr virus in multiple sclerosis.

PubMed

Abdelrahman, Hisham S; Selim, Heba S; Hashish, Mona H; Sultan, Lobna I

2014-08-01

Multiple sclerosis (MS) is an inflammatory disorder of the central nervous system. Many diseases are associated with Epstein-Barr virus (EBV) infection, such as infectious mononucleosis and many types of malignancies, and it is thought to be related to some diseases of autoimmune origin, such as rheumatoid arthritis, systemic lupus erythematosis, and others. The present study aimed to assess EBV in patients with MS. This case-control study was conducted from October 2012 to September 2013 on 75 MS patients and non-MS controls. Both were tested quantitatively for immunoglobulin G (IgG) antibodies against Epstein-Barr nuclear antigen-1 (EBNA1) and viral capsid antigen (VCA) using the enzyme linked immunosorbent assay technique. Seventy MS patients (93.3%) were positive for EBNA1 IgG compared with 68 controls (90.7%). In MS patients, the mean EBNA1 IgG serum level was 310.91 (±131.05) U/ml; meanwhile, among controls the mean serum EBNA IgG level was 177.81 (±104.98) U/ml.All patients with MS were positive for VCA IgG, whereas only 60 (80.0%) controls were positive. In the MS group, the VCA IgG mean level was 302.19 (±152.11) U/ml compared with 167.94 (±111.79) U/ml in controls. The differences in the serum levels of both markers between the two groups were statistically significant (P<0.001). EBV proved to have a unique immunological pattern in MS patients when compared with non-MS controls. Further studies for more confirmation of the relation between EBV and MS on a large scale are recommended.

Development and evaluation of antibody-capture immunoassays for detection of Lassa virus nucleoprotein-specific immunoglobulin M and G.

PubMed

Gabriel, Martin; Adomeh, Donatus I; Ehimuan, Jacqueline; Oyakhilome, Jennifer; Omomoh, Emmanuel O; Ighodalo, Yemisi; Olokor, Thomas; Bonney, Kofi; Pahlmann, Meike; Emmerich, Petra; Lelke, Michaela; Brunotte, Linda; Ölschläger, Stephan; Thomé-Bolduan, Corinna; Becker-Ziaja, Beate; Busch, Carola; Odia, Ikponmwosa; Ogbaini-Emovon, Ephraim; Okokhere, Peter O; Okogbenin, Sylvanus A; Akpede, George O; Schmitz, Herbert; Asogun, Danny A; Günther, Stephan

2018-03-01

The classical method for detection of Lassa virus-specific antibodies is the immunofluorescence assay (IFA) using virus-infected cells as antigen. However, IFA requires laboratories of biosafety level 4 for assay production and an experienced investigator to interpret the fluorescence signals. Therefore, we aimed to establish and evaluate enzyme-linked immunosorbent assays (ELISA) using recombinant Lassa virus nucleoprotein (NP) as antigen. The IgM ELISA is based on capturing IgM antibodies using anti-IgM, and the IgG ELISA is based on capturing IgG antibody-antigen complexes using rheumatoid factor or Fc gamma receptor CD32a. Analytical and clinical evaluation was performed with 880 sera from Lassa fever endemic (Nigeria) and non-endemic (Ghana and Germany) areas. Using the IFA as reference method, we observed 91.5-94.3% analytical accuracy of the ELISAs in detecting Lassa virus-specific antibodies. Evaluation of the ELISAs for diagnosis of Lassa fever on admission to hospital in an endemic area revealed a clinical sensitivity for the stand-alone IgM ELISA of 31% (95% CI 25-37) and for combined IgM/IgG detection of 26% (95% CI 21-32) compared to RT-PCR. The specificity of IgM and IgG ELISA was estimated at 96% (95% CI 93-98) and 100% (95% CI 99-100), respectively, in non-Lassa fever patients from non-endemic areas. In patients who seroconverted during follow-up, Lassa virus-specific IgM and IgG developed simultaneously rather than sequentially. Consistent with this finding, isolated IgM reactivity, i.e. IgM in the absence of IgG, had no diagnostic value. The ELISAs are not equivalent to RT-PCR for early diagnosis of Lassa fever; however, they are of value in diagnosing patients at later stage. The IgG ELISA may be useful for epidemiological studies and clinical trials due its high specificity, and the higher throughput rate and easier operation compared to IFA.

Development and characterization of an effective food allergy model in Brown Norway rats.

PubMed

Abril-Gil, Mar; Garcia-Just, Alba; Pérez-Cano, Francisco J; Franch, Àngels; Castell, Margarida

2015-01-01

Food allergy (FA) is an adverse health effect produced by the exposure to a given food. Currently, there is no optimal animal model of FA for the screening of immunotherapies or for testing the allergenicity of new foods. The aim of the present study was to develop an effective and rapid model of FA in Brown Norway rats. In order to establish biomarkers of FA in rat, we compared the immune response and the anaphylactic shock obtained in this model with those achieved with only intraperitoneal immunization. Rats received an intraperitoneal injection of ovalbumin (OVA) with alum and toxin from Bordetella pertussis, and 14 days later, OVA by oral route daily for three weeks (FA group). A group of rats receiving only the i.p. injection (IP group) were also tested. Serum anti-OVA IgE, IgG1, IgG2a, IgG2b and IgA antibodies were quantified throughout the study. After an oral challenge, body temperature, intestinal permeability, motor activity, and mast cell protease II (RMCP-II) levels were determined. At the end of the study, anti-OVA intestinal IgA, spleen cytokine production, lymphocyte composition of Peyer's patches and mesenteric lymph nodes, and gene expression in the small intestine were quantified. Serum OVA-specific IgG1, IgG2a and IgG2b concentrations rose with the i.p. immunization but were highly augmented after the oral OVA administration. Anti-OVA IgE increased twofold during the first week of oral OVA gavage. The anaphylaxis in both IP and FA groups decreased body temperature and motor activity, whereas intestinal permeability increased. Interestingly, the FA group showed a much higher RMCP II serum protein and intestinal mRNA expression. These results show both an effective and relatively rapid model of FA assessed by means of specific antibody titres and the high production of RMCP-II and its intestinal gene expression.

Development and Characterization of an Effective Food Allergy Model in Brown Norway Rats

PubMed Central

Abril-Gil, Mar; Garcia-Just, Alba; Pérez-Cano, Francisco J.; Franch, Àngels; Castell, Margarida

2015-01-01

Background Food allergy (FA) is an adverse health effect produced by the exposure to a given food. Currently, there is no optimal animal model of FA for the screening of immunotherapies or for testing the allergenicity of new foods. Objective The aim of the present study was to develop an effective and rapid model of FA in Brown Norway rats. In order to establish biomarkers of FA in rat, we compared the immune response and the anaphylactic shock obtained in this model with those achieved with only intraperitoneal immunization. Methods Rats received an intraperitoneal injection of ovalbumin (OVA) with alum and toxin from Bordetella pertussis, and 14 days later, OVA by oral route daily for three weeks (FA group). A group of rats receiving only the i.p. injection (IP group) were also tested. Serum anti-OVA IgE, IgG1, IgG2a, IgG2b and IgA antibodies were quantified throughout the study. After an oral challenge, body temperature, intestinal permeability, motor activity, and mast cell protease II (RMCP-II) levels were determined. At the end of the study, anti-OVA intestinal IgA, spleen cytokine production, lymphocyte composition of Peyer’s patches and mesenteric lymph nodes, and gene expression in the small intestine were quantified. Results Serum OVA-specific IgG1, IgG2a and IgG2b concentrations rose with the i.p. immunization but were highly augmented after the oral OVA administration. Anti-OVA IgE increased twofold during the first week of oral OVA gavage. The anaphylaxis in both IP and FA groups decreased body temperature and motor activity, whereas intestinal permeability increased. Interestingly, the FA group showed a much higher RMCP II serum protein and intestinal mRNA expression. Conclusions These results show both an effective and relatively rapid model of FA assessed by means of specific antibody titres and the high production of RMCP-II and its intestinal gene expression. PMID:25923134

HIV-Specific Functional Antibody Responses in Breast Milk Mirror Those in Plasma and Are Primarily Mediated by IgG Antibodies ▿

PubMed Central

Fouda, Genevieve G.; Yates, Nicole L.; Pollara, Justin; Shen, Xiaoying; Overman, Glenn R.; Mahlokozera, Tatenda; Wilks, Andrew B.; Kang, Helen H.; Salazar-Gonzalez, Jesus F.; Salazar, Maria G.; Kalilani, Linda; Meshnick, Steve R.; Hahn, Beatrice H.; Shaw, George M.; Lovingood, Rachel V.; Denny, Thomas N.; Haynes, Barton; Letvin, Norman L.; Ferrari, Guido; Montefiori, David C.; Tomaras, Georgia D.; Permar, Sallie R.

2011-01-01

Despite months of mucosal virus exposure, the majority of breastfed infants born to HIV-infected mothers do not become infected, raising the possibility that immune factors in milk inhibit mucosal transmission of HIV. HIV Envelope (Env)-specific antibodies are present in the milk of HIV-infected mothers, but little is known about their virus-specific functions. In this study, HIV Env-specific antibody binding, autologous and heterologous virus neutralization, and antibody-dependent cell cytotoxicity (ADCC) responses were measured in the milk and plasma of 41 HIV-infected lactating women. Although IgA is the predominant antibody isotype in milk, HIV Env-specific IgG responses were higher in magnitude than HIV Env-specific IgA responses in milk. The concentrations of anti-HIV gp120 IgG in milk and plasma were directly correlated (r = 0.75; P < 0.0001), yet the response in milk was 2 logarithm units lower than in plasma. Similarly, heterologous virus neutralization (r = 0.39; P = 0.010) and ADCC activity (r = 0.64; P < 0.0001) in milk were directly correlated with that in the systemic compartment but were 2 log units lower in magnitude. Autologous neutralization was rarely detected in milk. Milk heterologous virus neutralization titers correlated with HIV gp120 Env-binding IgG responses but not with IgA responses (r = 0.71 and P < 0.0001, and r = 0.17 and P = 0.30). Moreover, IgGs purified from milk and plasma had equal neutralizing potencies against a tier 1 virus (r = 0.65; P < 0.0001), whereas only 1 out of 35 tested non-IgG milk fractions had detectable neutralization. These results suggest that plasma-derived IgG antibodies mediate the majority of the low-level HIV neutralization and ADCC activity in breast milk. PMID:21734046

Specific memory B cell response and participation of CD4+ central and effector memory T cells in mice immunized with liposome encapsulated recombinant NE protein based Hepatitis E vaccine candidate.

PubMed

Kulkarni, Shruti P; Thanapati, Subrat; Arankalle, Vidya A; Tripathy, Anuradha S

2016-11-21

Liposome encapsulated neutralizing epitope protein of Hepatitis E virus (HEV), rNEp, our Hepatitis E vaccine candidate, was shown to be immunogenic and safe in pregnant and non-pregnant mice and yielded sterilizing immunity in rhesus monkeys. The current study in Balb/c mice assessed the levels and persistence of anti-HEV IgG antibodies by ELISA, frequencies of B, memory B, T and memory T cells by flow cytometry and HEV-specific IgG secreting memory B cells by ELISPOT till 420days post immunization (PI) with 5?g rNEp encapsulated in liposome based adjuvant (2 doses, 4weeks apart). Mice immunized with a lower dose (1?g) were assessed only for anamnestic response post booster dose. Vaccine candidate immunized mice (5?g dose) elicited strong anti-HEV IgG response that was estimated to persist for lifetime. At day 120 PI, frequency of memory B cells was higher in immunized mice than those receiving adjuvant alone. Anti-HEV IgG titers were lower in mice immunized with 1?g dose. A booster dose yielded a heightened antibody response in mice with both high (>800GMT, 5?g) and low (?100GMT, 1?g) anti-HEV IgG titers. At day 6th post booster dose, HEV-specific antibody secreting plasma cells (ASCs) were detected in 100% and 50% of mice with high and low anti-HEV IgG titers, respectively, whereas the frequencies of CD4 + central and effector memory T cells were high in mice with high anti-HEV IgG titers only. Taken together, the vaccine candidate effectively generates persistent and anamnestic antibody response, elicits participation of CD4 + memory T cells and triggers memory B cells to differentiate into ASCs upon boosting. This approach of assessing the immunogenicity of vaccine candidate could be useful to explore the longevity of HEV-specific memory response in future HEV vaccine trials in human. Copyright © 2016. Published by Elsevier Ltd.

Seropositivity of toxoplasmosis in patients with schizophrenia.

PubMed

El-Sahn, Amel A; Shatat, Hanan Z; Ghitany, Engy M

2005-01-01

Recent studies indicate that infectious agents may contribute to some cases of schizophrenia. In animals, infections with Toxoplasma gondii can alter behavior and neurotransmitter function. In humans, acute infection can produce psychotic symptoms similar to those displayed by persons with schizophrenia. In the present study, an enzyme immunoassay (EIA) was employed to measure the level of Toxoplasma IgG antibodies in serum samples from 75 patients of schizophrenia and 85 matched controls. Percentage of positive sera for Toxoplasma IgG antibodies was significantly higher in schizophrenic cases than controls (80% vs. 52.9% respectively). Infection increased with age in both groups and no significant association was found with sex. No association was found with duration of illness or presence of family history of schizophrenia. Circumstantial evidence indicates that infection with Toxoplasma gondii may lead to some cases of schizophrenia.

Serum anti-Helicobacter pylori immunoglobulin G titer correlates with grade of histological gastritis, mucosal bacterial density, and levels of serum biomarkers.

PubMed

Tu, Huakang; Sun, Liping; Dong, Xiao; Gong, Yuehua; Xu, Qian; Jing, Jingjing; Yuan, Yuan

2014-03-01

OBJECTIVE. Clinical implications of serum anti-Helicobacter pylori immunoglobulin G (IgG) titer were unclear. This study investigated the associations of serum anti-H. pylori IgG titer with grade of histological gastritis, mucosal bacterial density and levels of serum biomarkers, including pepsinogen (PG) I, PGII, PGI/II ratio and gastrin-17. MATERIAL AND METHODS. Study participants were from a screening program in northern China. Serum anti-H. pylori IgG measurements were available for 5922 patients with superficial gastritis. Serum anti-H. pylori IgG titer and serum biomarkers were measured using ELISA, and gastric biopsies were evaluated using standardized criteria. RESULTS. In patients with mild, moderate or severe superficial gastritis, the mean serum anti-H. pylori IgG titers were 17.3, 33.4 and 54.4 EIU (p for trend < 0.0001), respectively. As mucosal H. pylori density score increased from 0 to 3, the mean serum anti-H. pylori IgG titers also increased from 24.7 to 44.8 EIU (p for trend < 0.0001). Serum anti-H. pylori IgG titer was associated positively with serum PGI, PGII and gastrin-17 concentrations and negatively with PGI/II ratio, and the association was the strongest for PGII. The mean PGII concentration of the patients in the highest quartile of IgG titer was twice the mean concentration of the patients in the lowest quartile (17.2 vs. 8.6 EIU, p < 0.0001). CONCLUSIONS. Our results suggest that serum anti-H. pylori IgG titer was associated positively with grade of histological gastritis, mucosal bacterial density and concentrations of serum PGI, PGII and gastrin-17, and negatively with PGI/II ratio.

Effect of Therapeutic Plasma Exchange on Immunoglobulins in Myasthenia Gravis

PubMed Central

Guptill, Jeffrey T.; Juel, Vern C.; Massey, Janice M.; Anderson, Amanda C.; Chopra, Manisha; Yi, John S.; Esfandiari, Ehsanollah; Buchanan, Tim; Smith, Bryan; Atherfold, Paul; Jones, Emma; Howard, James F.

2017-01-01

An integrated understanding of therapeutic plasma exchange (TPE) effects on immunoglobulins, autoantibodies, and natural or acquired (vaccine) protective antibodies in patients with autoimmune myasthenia gravis (MG) is lacking. Prior studies measured TPE effects in healthy volunteers or heterogeneous autoimmune diseases populations. We prospectively profiled plasma IgA, IgM, IgG, IgG subclasses (IgG1-4), acetylcholine receptor autoantibodies (AChR+), and protective antibodies in patients with AChR+ MG receiving TPE for an exacerbation. TPE was performed according to institutional practice and patients were profiled for up to 12 weeks. Ten patients were enrolled (median age=72.9 years; baseline MG-Composite=21; median TPE treatments=6 during their first course) and all improved. The maximum decrease in all immunoglobulins, including AChR autoantibodies, was achieved on the final day of the first TPE course (approximately 60–70% reduction). Three weeks post-TPE mean AChR autoantibody, total IgG, IgG1 and IgG2 titers were below the reference range and had not recovered to within 20% of baseline, whereas other measured immunoglobulins approached baseline values. We did not generally observe an “overshoot” of immunoglobulins above pre-TPE levels or accelerated recovery of pathologic AChR autoantibodies. Protective antibody profiles showed similar patterns as other IgGs and were detectable at levels associated with protection from infection. A slow return to baseline for IgGs (except IgG3) was observed, and we did not observe any obvious effect of concomitant medications on this recovery. Collectively, these findings enhance our understanding of the immunological effects of TPE and further supports the concept of rapid immunoglobulin depletion for the treatment of patients with MG. PMID:27684107

Effect of therapeutic plasma exchange on immunoglobulins in myasthenia gravis.

PubMed

Guptill, Jeffrey T; Juel, Vern C; Massey, Janice M; Anderson, Amanda C; Chopra, Manisha; Yi, John S; Esfandiari, Ehsanollah; Buchanan, Tim; Smith, Bryan; Atherfold, Paul; Jones, Emma; Howard, James F

2016-11-01

An integrated understanding of therapeutic plasma exchange (TPE) effects on immunoglobulins, autoantibodies, and natural or acquired (vaccine) protective antibodies in patients with autoimmune myasthenia gravis (MG) is lacking. Prior studies measured TPE effects in healthy volunteers or heterogeneous autoimmune disease populations. We prospectively profiled plasma IgA, IgM, IgG, IgG subclasses (IgG1-4), acetylcholine receptor autoantibodies (AChR+), and protective antibodies in patients with AChR + MG receiving TPE for an exacerbation. TPE was performed according to institutional practice and patients were profiled for up to 12 weeks. Ten patients were enrolled (median age = 72.9 years; baseline MG-Composite = 21; median TPE treatments = 6 during their first course) and all improved. The maximum decrease in all immunoglobulins, including AChR autoantibodies, was achieved on the final day of the first TPE course (∼60-70% reduction). Three weeks post-TPE, mean AChR autoantibody, total IgG, IgG1, and IgG2 titers were below the reference range and had not recovered within 20% of baseline, whereas other measured immunoglobulins approached baseline values. We did not generally observe an "overshoot" of immunoglobulins above pre-TPE levels or accelerated recovery of pathologic AChR autoantibodies. Protective antibody profiles showed similar patterns as other IgGs and were detectable at levels associated with protection from infection. A slow return to baseline for IgGs (except IgG3) was observed, and we did not observe any obvious effect of concomitant medications on this recovery. Collectively, these findings enhance our understanding of the immunological effects of TPE and further support the concept of rapid immunoglobulin depletion for the treatment of patients with MG.

Evaluation of Antigen-Specific IgM and IgG Production during an In Vitro Peripheral Blood Mononuclear Cell Culture Assay.

PubMed

Matsuda, Yoshiko; Imamura, Ryoichi; Takahara, Shiro

2017-01-01

The recent attention given to diseases associated with memory B-cell (mBC)-produced antibodies (Abs) suggests the need for a similar in vitro assay to evaluate the functions of mBCs. Here, we cultured peripheral blood mononuclear cells (PBMCs) with the intent to collect mBC-derived Abs in vitro and maintain their cell-cell contact-dependent interactions with helper T-cells. PBMCs were cultured with interleukin (IL)-21, CpG-oligodeoxynucleotides (ODN), phorbol myristate acetate (PMA), and phytohemagglutinin/leucoagglutinin (PHA-L) in 24-well flat-bottom plates (5 × 10 5  cells/well). A culture supernatant analysis of PBMCs from healthy donors ( n  = 10) indicated that antigen-specific IgM Ab levels in a PBMC culture supernatant might be better able to demonstrate the antigen sensitization status in a smaller peripheral blood sample, compared to IgG because Epstein-Barr virus-specific IgM mBCs circulate peripherally at a significantly higher frequency once antiviral humoral immunity has stabilized. Thus, our in vitro assay demonstrated the potential significance of antigen-specific IgM Ab production in the culture supernatants. Furthermore, an analysis of cultured PBMCs from allograft kidney recipients ( n  = 16) sensitized with de novo donor-specific human leukocyte antigen (HLA)-specific Abs (DSAs) showed that IgM-type HLA-specific Abs were detected mainly from the culture supernatants from PBMCs of patients with stable graft function, whereas IgG isotype HLA Abs were detectable only from patients with biopsy-proven antibody-mediated rejection. In other words, these IgG isotype Abs also represented an activated humoral immune response in vivo . Additionally, IgM- and IgG-expressing mBCs from healthy donors ( n  = 5) were cultured with IL-21, CpG-ODN, and a supernatant produced by stimulating CD19 + B-cell-depleted PBMCs with PHA-L and PMA in 24-well flat-bottom plates (1 × 10 5  cells/well), and the resulting in vitro analysis provided some information regarding the biological processes of IgG and IgM mBCs in peripheral blood. Taken together, our findings suggest that antigen-specific Ab subtype analyses of supernatants from cultured PBMCs might more effectively and accurately reflect a patient's Ab-associated pathological condition vs. than serum IgG and IgM levels.

Identification of two allelic IgG1 C(H) coding regions (Cgamma1) of cat.

PubMed

Kanai, T H; Ueda, S; Nakamura, T

2000-01-31

Two types of cDNA encoding IgG1 heavy chain (gamma1) were isolated from a single domestic short-hair cat. Sequence analysis indicated a higher level of similarity of these Cgamma1 sequences to human Cgamma1 sequence (76.9 and 77.0%) than to mouse sequence (70.0 and 69.7%) at the nucleotide level. Predicted primary structures of both the feline Cgamma1 genes, designated as Cgamma1a and Cgamma1b, were similar to that of human Cgamma1 gene, for instance, as to the size of constant domains, the presence of six conserved cysteine residues involved in formation of the domain structure, and the location of a conserved N-linked glycosylation site. Sequence comparison between the two alleles showed that 7 out of 10 nucleotide differences were within the C(H)3 domain coding region, all leading to nonsynonymous changes in amino acid residues. Partial sequence analysis of genomic clones showed three nucleotide substitutions between the two Cgamma1 alleles in the intron between the CH2 and C(H)3 domain coding regions. In 12 domestic short-hair cats used in this study, the frequency of Cgamma1a allele (62.5%) was higher than that of the Cgamma1b allele (37.5%).

Combined glyco- and protein-Fc engineering simultaneously enhance cytotoxicity and half-life of a therapeutic antibody.

PubMed

Monnet, Céline; Jorieux, Sylvie; Souyris, Nathalie; Zaki, Ouafa; Jacquet, Alexandra; Fournier, Nathalie; Crozet, Fabien; de Romeuf, Christophe; Bouayadi, Khalil; Urbain, Rémi; Behrens, Christian K; Mondon, Philippe; Fontayne, Alexandre

2014-01-01

While glyco-engineered monoclonal antibodies (mAbs) with improved antibody-dependent cell-mediated cytotoxicity (ADCC) are reaching the market, extensive efforts have also been made to improve their pharmacokinetic properties to generate biologically superior molecules. Most therapeutic mAbs are human or humanized IgG molecules whose half-life is dependent on the neonatal Fc receptor FcRn. FcRn reduces IgG catabolism by binding to the Fc domain of endocytosed IgG in acidic lysosomal compartments, allowing them to be recycled into the blood. Fc-engineered mAbs with increased FcRn affinity resulted in longer in vivo half-life in animal models, but also in healthy humans. These Fc-engineered mAbs were obtained by alanine scanning, directed mutagenesis or in silico approach of the FcRn binding site. In our approach, we applied a random mutagenesis technology (MutaGen™) to generate mutations evenly distributed over the whole Fc sequence of human IgG1. IgG variants with improved FcRn-binding were then isolated from these Fc-libraries using a pH-dependent phage display selection process. Two successive rounds of mutagenesis and selection were performed to identify several mutations that dramatically improve FcRn binding. Notably, many of these mutations were unpredictable by rational design as they were located distantly from the FcRn binding site, validating our random molecular approach. When produced on the EMABling(®) platform allowing effector function increase, our IgG variants retained both higher ADCC and higher FcRn binding. Moreover, these IgG variants exhibited longer half-life in human FcRn transgenic mice. These results clearly demonstrate that glyco-engineering to improve cytotoxicity and protein-engineering to increase half-life can be combined to further optimize therapeutic mAbs.

mTOR pathway is activated in endothelial cells from patients with Takayasu arteritis and is modulated by serum immunoglobulin G.

PubMed

Hadjadj, Jérôme; Canaud, Guillaume; Mirault, Tristan; Samson, Maxime; Bruneval, Patrick; Régent, Alexis; Goulvestre, Claire; Witko-Sarsat, Véronique; Costedoat-Chalumeau, Nathalie; Guillevin, Loïc; Mouthon, Luc; Terrier, Benjamin

2018-06-01

Takayasu arteritis (TA) and GCA are large-vessel vasculitides characterized by vascular remodelling involving endothelial cells (ECs) and vascular smooth muscle cells. Mammalian target of rapamycin (mTOR) pathway has been involved in vascular remodelling. We hypothesized that the mTOR pathway was involved in the pathogenesis of large-vessel vasculitis. We used IF analysis on aortic and temporal artery biopsies from patients with TA and GCA to assess the involvement of the mTOR pathway and searched for antibodies targeting ECs in serum by IIF and cellular ELISA. We evaluated in vitro the effect of purified IgG from patients on mTOR pathway activation and cell proliferation. IF analyses on tissues revealed that both mTORC1 and mTORC2 are activated specifically in ECs from TA patients but not in ECs from GCA patients and healthy controls (HCs). Using IIF and ELISA, we observed higher levels of antibodies binding to ECs in TA patients compared with GCA patients and HCs. Using western blot, we demonstrated that purified IgG from TA patients caused mTORC1 activation in ECs, whereas this effect was not observed with purified IgG from GCA patients or HCs. Purified IgG from TA patients induced a significant EC proliferation compared with to GCA and HC IgG, and this effect was decreased after EC exposure with sirolimus, a specific mTOR inhibitor and PI3K inhibitor. Our results suggest that antibodies targeting ECs drive endothelial remodelling in TA through activation of the mTOR pathway, but not in GCA. Inhibition of the mTOR pathway could represent a therapeutic option in TA.

Evaluation of prevalence, immunogenicity and efficacy of FyuA iron receptor in uropathogenic Escherichia coli isolates as a vaccine target against urinary tract infection.

PubMed

Habibi, Mehri; Asadi Karam, Mohammad Reza; Bouzari, Saeid

2017-09-01

Uropathogenic Escherichia coli (UPEC) are among the most prevalent agents of urinary tract infections (UTIs). Antibiotic resistance reaches the need for alternative treatment approaches such as vaccination against UTIs. There is no ideal vaccine against UTIs, thus there is a need to evaluate different targets of uropathogens against UTIs. Ferric scavenger receptor FyuA in UPEC has the properties of an ideal vaccine candidate against UTIs. In the present study, the prevalence of FyuA among UPEC isolates, its immunogenicity with and without alum adjuvant, and its efficacy against experimental UTI were assessed. Totally, fyuA gene was present in 77% of the UPEC isolates tested. Alignments of FyuA exhibited a high degree of conservation among different submitted UPEC isolates in GenBank. The bioinformatics studies showed the high confidence value and stability of the FyuA structure. SDS-PAGE and Western blot confirmed the purification of FyuA with high yield by nickel resins. Mice vaccinated subcutaneously with the FyuA induced a significantly higher humoral response (total IgG, IgG1 and IgG2a) than control mice that alum enhanced these responses. The FuyA alone showed the ability to reduce the colonization of UPEC in bladder and kidney of mice as compared to the control group. But the addition of alum to FyuA increased the protection level against UPEC in these organs. Since, FyuA induced significant IgG1 (Th2) and IgG2a (Th1) responses and protected the mice against experimental UTI, it could be a promising target against UPEC infections. Copyright © 2017 Elsevier Ltd. All rights reserved.

Insights from LGI1 and CASPR2 potassium channel complex autoantibody subtyping.

PubMed

Klein, Christopher J; Lennon, Vanda A; Aston, Paula A; McKeon, Andrew; O'Toole, Orna; Quek, Amy; Pittock, Sean J

2013-02-01

To determine, in patients identified as seropositive for neuronal voltage-gated potassium channel (VGKC) complex autoantibodies, the spectrum of clinical presentations and frequency of leucine-rich glioma-inactivated protein 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) as defined antigenic neuronal targets in the VGKC macromolecular complex. Retrospective cohort study. Clinical practice, Mayo Clinic Neuroimmunology Laboratory and Department of Neurology. A total of 54 853 patients were evaluated, of whom 1992 were found to be VGKC complex IgG positive. From June 1, 2008, to June 30, 2010, comprehensive service serologic evaluation performed on 54853 patients with unexplained neurologic symptoms identified 1992 patients (4%) who were positive for VGKC complex IgG (values ≥ 0.03 nmol/L). Among 316 seropositive patients evaluated clinically at our institution, 82 (26%) were seropositive for LGI1 IgG and/or CASPR2 IgG. Of these 82 patients, 27% had low (0.03-0.09 nmol/L), 51% had medium (0.10-0.99 nmol/L), and 22% had high (≥ 1.00 nmol/L) VGKC complex IgG values. Leucine-rich glioma-inactivated protein 1 IgG positivity was associated with higher VGKC complex IgG values (P< .001) and cortical presentations (P< .001); CASPR2 IgG was associated with peripheral motor excitability (P= .009). However, neither autoantibody was pathognomonic for a specific neurologic presentation or correlated significantly with cancer. Neurologic phenotypes were diverse. Cerebrocortical manifestations (including cognitive impairment and seizures) were recorded in 76% of patients with LGI1 IgG alone (n=46) and 29% with CASPR2 IgG alone (n=28). Peripheral motor hyperexcitability was found in 21% of patients with CASPR2 IgG alone and 6.5% of patients with LGI1 IgG alone. The study emphasizes diverse and overlapping neurologic phenotypes across a range of VGKC complex IgG values and varying LGI1 IgG and CASPR2 IgG specificities. The frequent occurrence of LGI1 IgG and CASPR2 IgG in serum samples with low and medium VGKC complex IgG values supports the clinical significance of low values in clinical evaluation. Additional antigenic components of VGKC macromolecular complexes remain to be defined.

Insights From LGI1 and CASPR2 Potassium Channel Complex Autoantibody Subtyping

PubMed Central

Klein, Christopher J.; Lennon, Vanda A.; Aston, Paula A.; McKeon, Andrew; O’Toole, Orna; Quek, Amy; Pittock, Sean J.

2014-01-01

Objective: To determine, in patients identified as sero-positive for neuronal voltage-gated potassium channel (VGKC) complex autoantibodies, the spectrum of clinical presentations and frequency of leucine-rich glioma-inactivated protein 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) as defined antigenic neuronal targets in the VGKC macromolecular complex. Design: Retrospective cohort study. Setting: Clinical practice, Mayo Clinic Neuroimmunology Laboratory and Department of Neurology. Patients: A total of 54853 patients were evaluated, of whom 1992 were found to be VGKC complex IgG positive. Results: From June 1, 2008, to June 30, 2010, comprehensive service serologic evaluation performed on 54 853 patients with unexplained neurologic symptoms identified 1992 patients (4%) who were positive for VGKC complex IgG (values ≥0.03 nmol/L). Among 316 seropositive patients evaluated clinically at our institution, 82 (26%) were seropositive for LGI1 IgG and/or CASPR2 IgG. Of these 82 patients, 27% had low (0.03-0.09 nmol/L), 51% had medium (0.10-0.99 nmol/L), and 22% had high (≥1.00 nmol/L) VGKC complex IgG values. Leucine-rich glioma-inactivated protein 1 IgG positivity was associated with higher VGKC complex IgG values (P<.001) and cortical presentations (P<.001); CASPR2 IgG was associated with peripheral motor excitability (P=.009). However, neither autoantibody was pathognomonic for a specific neurologic presentation or correlated significantly with cancer. Neurologic phenotypes were diverse. Cerebrocortical manifestations (including cognitive impairment and seizures) were recorded in 76% of patients with LGI1 IgG alone (n=46) and 29% with CASPR2 IgG alone (n=28). Peripheral motor hyperexcitability was found in 21% of patients with CASPR2 IgG alone and 6.5% of patients with LGI1 IgG alone. Conclusions: The study emphasizes diverse and overlapping neurologic phenotypes across a range of VGKC complex IgG values and varying LGI1 IgG and CASPR2 IgG specificities. The frequent occurrence of LGI1 IgG and CASPR2 IgG in serum samples with low and medium VGKC complex IgG values supports the clinical significance of low values in clinical evaluation. Additional antigenic components of VGKC macromolecular complexes remain to be defined. PMID:23407760

Anti-neuropeptide Y plasma immunoglobulins in relation to mood and appetite in depressive disorder.

PubMed

Garcia, Frederico D; Coquerel, Quentin; do Rego, Jean-Claude; Cravezic, Aurore; Bole-Feysot, Christine; Kiive, Evelyn; Déchelotte, Pierre; Harro, Jaanus; Fetissov, Sergueï O

2012-09-01

Depression and eating disorders are frequently associated, but the molecular pathways responsible for co-occurrence of altered mood, appetite and body weight are not yet fully understood. Neuropeptide Y (NPY) has potent antidepressant and orexigenic properties and low central NPY levels have been reported in major depression. In the present study, we hypothesized that in patients with major depression alteration of mood, appetite and body weight may be related to NPY-reactive autoantibodies (autoAbs). To test this hypothesis, we compared plasma levels and affinities of NPY-reactive autoAbs between patients with major depression and healthy controls. Then, to evaluate if changes of NPY autoAb properties can be causally related to altered mood and appetite, we developed central and peripheral passive transfer models of human autoAbs in mice and studied depressive-like behavior in forced-swim test and food intake. We found that plasma levels of NPY IgG autoAbs were lower in patients with moderate but not with mild depression correlating negatively with the Montgomery-Åsberg Depression Rating Scale scores and with immobility time of the forced-swim test in mice after peripheral injection of autoAbs. No significant differences in NPY IgG autoAb affinities between patients with depression and controls were found, but higher affinity of IgG autoAbs for NPY was associated with lower body mass index and prevented NPY-induced orexigenic response in mice after their central injection. These data suggest that changes of plasma levels of anti-NPY autoAbs are relevant to altered mood, while changes of their affinity may participate in altered appetite and body weight in patients with depressive disorder. Copyright © 2012 Elsevier Ltd. All rights reserved.

Seroepidemiology of Helicobacter Pylori Infection in Pregnant Women in Rural Durango, Mexico

PubMed Central

Alvarado-Esquivel, Cosme

2013-01-01

The seroepidemiology of Helicobacter pylori infection in pregnant women in Durango, Mexico is largely unknown. The prevalence of anti-H. pylori IgG antibodies was examined in 343 pregnant women living in rural areas in 7 municipalities in Durango State, Mexico, using enzyme-linked immunosorbent assays (ELISA). A correlation of H. pylori seropositivity with socio-demographic, obstetric and behavioral characteristics of pregnant women was also assessed. In total, 179 (52.2%) of the 343 pregnant women (mean age, 24.2 ± 5.9 years) had H. pylori IgG antibodies, 75 (41.9%) of whom had H. pylori IgG antibody levels higher than 100 U/mL. The seroprevalence of H. pylori infection varied from 33.3% to 65% among municipalities. In contrast, the seroprevalence was comparable among women regardless their age, educational level, occupation, socioeconomic status, animal contacts, foreign travel, eating habits, contact with soil, crowding, sanitary conditions at home and educational level of the head of their families. Multivariant analysis of socio-demographic and behavioral variables showed that H. pylori seropositivity was associated with municipality (OR=1.12; 95% CI: 1.01–1.24; P=0.02). Of the obstetric characteristics, the seroprevalence of H. pylori infection increased significantly with the number of pregnancies and deliveries but not with the number of cesarean sections or miscarriages. Rural pregnant women in Durango had a lower seroprevalence of H. pylori infection than those from populations in developing countries. Results support a variability of H. pylori seroprevalence within a region. Further research at a municipal level might help to understand the epidemiology of H. pylori infection. PMID:24711758

Humoral and B-cell memory responses in children five years after pertussis acellular vaccine priming.

PubMed

Carollo, Maria; Pandolfi, Elisabetta; Tozzi, Alberto Eugenio; Buisman, Anne-Marie; Mascart, Françoise; Ausiello, Clara Maria

2014-04-11

The resurgence of pertussis suggests the need for greater efforts in understanding the long-lasting protective responses induced by vaccination. In this paper we dissect the persistence of humoral and B-cell memory responses induced by primary vaccination with two different acellular pertussis (aP) vaccines, hexavalent Hexavac(®) vaccine (Hexavac) (Sanofi Pasteur MSD) and Infanrix hexa(®) (Infanrix) (GlaxoSmithKline Biologicals). We evaluated the specific immune responses in the two groups of children, 5 years after primary vaccination by measuring the persistence of IgG and antibody secreting cells (ASC) specific for vaccine antigens. Part of the enrolled children received only primary vaccination, while others had the pre-school boost dose. A similar level of antigen-specific IgG and ASC was found in Infanrix and Hexavac vaccinated children. The mean IgG levels were significantly higher in children that received the pre-school boost as compared with children that did not receive the boost dose. A longer persistence after the pre-school boost of IgG-Pertussis Toxin (PT) and IgG-pertactin levels was observed in Infanrix primed children, but it was not statistically significant. More than 80% of children presented a positive ASC B memory response. Around 50% of children still presented protective IgG-PT levels which are reduced to 36% in no-boosted children. The pre-school booster dose restores the percentage of protected children above 50%. In conclusion our data underline the importance of giving a booster dose 5 years after primary vaccination and suggest the need for a new vaccine able to induce a long lasting protective response. Copyright © 2014 Elsevier Ltd. All rights reserved.

Estimation of Serum Triglycerides, Serum Cholesterol, Total Protein, IgG Levels in Chronic Periodontitis Affected Elderly Patients: A Cross-Sectional Study

PubMed Central

Saravanan, A. V.; Ravishankar, P. L.; Kumar, Pradeep; Rajapandian, K.; Kalaivani, V.; Rajula, M. Prem Blaisie

2017-01-01

Aim: The present study was conducted to evaluate the serum triglycerides, serum cholesterol, total protein, and IgG levels in elderly patients who were affected by periodontal disease. Materials and Methods: This study was conducted at the Rajah Muthiah Dental College and Hospital in the periodontics division. The study was conducted for a period of 3 months. This study is a prospective analytical study. Sixty individuals who were systemically healthy in the age group of 50 and above were included in this study. Control and experimental groups of 30 participants each were included. Plaque index, gingival index, probing pocket depth, and clinical attachment loss were recorded. Biochemical parameters such as serum cholesterol, serum triglycerides, total protein, and IgG levels were also evaluated and correlated with the periodontal parameters. Data was analyzed using SPSS version 16.0 (IBM Corp., Armonk, NY). The relationship between periodontal status and the biochemical parameters such as serum cholesterol, serum triglycerides, total protein, and IgG levels were evaluated by Student's t-test. Results: There was no significant difference in the plaque and gingival scores between the experimental and control group. It was observed that serum cholesterol level and total protein level was lower in participants suffering from chronic periodontitis. Triglycerides level was significantly elevated in the experimental group. IgG, a level which is not significant, concluded that there is no difference in control and experimental group. Conclusion: It was concluded from the results obtained from the study that there is an association between serum triglycerides, serum cholesterol, total protein, and periodontal disease. However, further longitudinal and well-controlled studies are required to evaluate the relationship between these biochemical parameters and periodontal disease. PMID:28462181

Estimation of Serum Triglycerides, Serum Cholesterol, Total Protein, IgG Levels in Chronic Periodontitis Affected Elderly Patients: A Cross-Sectional Study.

PubMed

Saravanan, A V; Ravishankar, P L; Kumar, Pradeep; Rajapandian, K; Kalaivani, V; Rajula, M Prem Blaisie

2017-01-01

The present study was conducted to evaluate the serum triglycerides, serum cholesterol, total protein, and IgG levels in elderly patients who were affected by periodontal disease. This study was conducted at the Rajah Muthiah Dental College and Hospital in the periodontics division. The study was conducted for a period of 3 months. This study is a prospective analytical study. Sixty individuals who were systemically healthy in the age group of 50 and above were included in this study. Control and experimental groups of 30 participants each were included. Plaque index, gingival index, probing pocket depth, and clinical attachment loss were recorded. Biochemical parameters such as serum cholesterol, serum triglycerides, total protein, and IgG levels were also evaluated and correlated with the periodontal parameters. Data was analyzed using SPSS version 16.0 (IBM Corp., Armonk, NY). The relationship between periodontal status and the biochemical parameters such as serum cholesterol, serum triglycerides, total protein, and IgG levels were evaluated by Student's t-test. There was no significant difference in the plaque and gingival scores between the experimental and control group. It was observed that serum cholesterol level and total protein level was lower in participants suffering from chronic periodontitis. Triglycerides level was significantly elevated in the experimental group. IgG, a level which is not significant, concluded that there is no difference in control and experimental group. It was concluded from the results obtained from the study that there is an association between serum triglycerides, serum cholesterol, total protein, and periodontal disease. However, further longitudinal and well-controlled studies are required to evaluate the relationship between these biochemical parameters and periodontal disease.

Periodontal treatment decreases levels of antibodies to Porphyromonas gingivalis and citrulline in patients with rheumatoid arthritis and periodontitis.

PubMed

Okada, Moe; Kobayashi, Tetsuo; Ito, Satoshi; Yokoyama, Tomoko; Abe, Asami; Murasawa, Akira; Yoshie, Hiromasa

2013-12-01

Porphyromonas gingivalis has been implicated as an etiologic agent of rheumatoid arthritis (RA) because of the expression of peptidylarginine deiminase. The present study evaluates whether periodontal treatment may affect serum antibodies to P. gingivalis and citrulline levels in relation to disease activity of RA. Fifty-five patients with RA were randomly assigned to receive oral hygiene instruction and supragingival scaling (treatment group, n = 26) or no periodontal treatment (control group, n = 29). Periodontal and rheumatologic parameters and serum levels of cytokine and inflammatory markers citrulline and immunoglobulin (Ig)G to P. gingivalis were examined at baseline and 8 weeks later. Both groups did not differ statistically in any parameters except percentage of sites with probing depth and clinical attachment level ≥ 4 mm at baseline. The treatment group exhibited a significantly greater decrease in disease activity score including 28 joints using C-reactive protein (DAS28-CRP) (P = 0.02), serum levels of IgG to P. gingivalis hemin binding protein (HBP)35 (P = 0.04), and citrulline (P = 0.02) than the control group. Serum levels of IgG to P. gingivalis HBP35 were significantly correlated positively with those of anti-cyclic citrullinated peptide antibodies (P = 0.0002). The same correlation was obtained between serum levels of IgG to P. gingivalis-sonicated extracts and those of rheumatoid factor (P = 0.02). These results suggest that supragingival scaling decreases DAS28-CRP and serum levels of IgG to P. gingivalis HBP35 and citrulline in patients with RA. These observations may reflect a role of P. gingivalis in the protein citrullination, which is related to the pathogenesis of RA.

Usefulness of anti-oxidized LDL antibody determination for assessment of clinical control in patients with heart failure.

PubMed

George, Jacob; Wexler, Dov; Roth, Arie; Barak, Tomer; Sheps, David; Keren, Gad

2006-01-01

It has been suggested that oxidative stress may play a role in the pathogenesis of heart failure, this may have potential implications for therapeutic strategies. However, measures of oxidative stress are subject to confounding inaccuracies. IgG antibodies to oxidized LDL reflect exposure to the lipoprotein over an extended period and may thus mirror oxidative stress over a prolonged time frame. Therefore, we tested the hypothesis that anti-oxLDL antibodies correlate with the control of heart failure (HF), as manifested by hospital admissions for cardiac dysfunction. One hundred and two consecutive patients attending the HF clinic with either systolic or diastolic HF were enrolled and the quality of clinical control was evaluated by assessing hospital admissions over the year prior to index determination of the oxidative stress marker. Antibodies to oxLDL were determined by ELISA and pro-BNP levels were also measured. Most patients (mean age 71.5 years) had systolic HF; mean NYHA functional class was 2.7 and mean left ventricular ejection fraction was 39.7%. Anti-oxLDL antibodies, but not pro-BNP, correlated significantly with mean NYHA score (averaged from all clinic visits in the year prior to blood testing), and with hospital admissions over the year prior to blood testing. Mean IgG anti-oxLDL antibody levels in patients with hospital admissions were 3.4 times higher than those in subjects not hospitalized over the previous year. IgG anti-oxLDL antibody levels correlate with the severity of HF.

Association between anti-beta2 glycoprotein I antibodies and renal glomerular C4d deposition in lupus nephritis patients with glomerular microthrombosis: a prospective study of 155 cases.

PubMed

Shen, Y; Chen, X-W; Sun, C-Y; Dai, M; Yan, Y-C; Yang, C-D

2010-09-01

Glomerular microthrombosis (GMT) is a common vascular change in patients with lupus nephritis (LN). The mechanism underlying GMT is still unknown. In our previous study, we found that the level of IgG anti-beta2 glycoprotein I (beta2GPI) antibodies was higher in the LN-GMT group than in the LN-non-GMT group, which indicated that anti-beta2GPI antibodies may play a role in GMT formation. Many studies have demonstrated that the activation of the classical complement pathway may play a critical role in fetal loss and aPL-induced thrombosis formation. To investigate whether complement activation plays a role in GMT formation and to evaluate its relationship with aPL, we prospectively investigated deposition of C4d in 155 renal biopsy specimens of LN patients. The results revealed a strong relationship between the intensity of glomerular C4d staining and the presence of microthrombi (p < 0.001). The detection rate of IgG anti-beta2GPI antibodies was higher in the LN-GMT group than in the LN-non-GMT group (p < 0.05). Further, the intensity of glomerular C4d staining was significantly related with IgG anti-beta2GPI antibodies (p < 0.05). The results of our study suggest that anti-beta2GPI antibodies may play a role in GMT formation, and this process might involve complement activation.

A comparison of immunogenicity and protective immunity against experimental plague by intranasal and/or combined with oral immunization of mice with attenuated Salmonella serovar Typhimurium expressing secreted Yersinia pestis F1 and V antigen

PubMed Central

Liu, Wen-Tssann; Hsu, Hui-Ling; Liang, Chung-Chih; Chuang, Chuan-Chang; Lin, Huang-Chi; Liu, Yu-Tien

2007-01-01

We investigated the relative immunogenicity and protective efficacy of recombinant X85MF1 and X85V strains of ΔcyaΔcrpΔasd-attenuated Salmonella Typhimurium expressing, respectively, secreted Yersinia pestis F1 and V antigens, following intranasal (i.n.) or i.n. combined with oral immunization for a mouse model. A single i.n. dose of 108 CFU of X85MF1 or X85V induced appreciable serum F1- or V-specific IgG titres, although oral immunization did not. Mice i.n. immunized three times (i.n. × 3) with Salmonella achieved the most substantial F1/V-specific IgG titres, as compared with corresponding titres for an oral-primed, i.n.-boosted (twice; oral-i.n. × 2) immunization regimen. The level of V-specific IgG was significantly greater than that of F1-specific IgG (P<0.001). Analysis of the IgG antibodies subclasses revealed comparable levels of V-specific Th-2-type IgG1 and Th-1-type IgG2a, and a predominance of F1-specific Th-1-type IgG2a antibodies. In mice immunized intranasally, X85V stimulated a greater IL-10-secreting-cell response in the lungs than did X85MF1, but impaired the induction of gamma-interferon-secreting cells. A program of i.n. × 3 and/or oral-i.n. × 2 immunization with X85V provided levels of protection against a subsequent lethal challenge with Y. pestis, of, respectively, 60% and 20%, whereas 80% protection was provided following the same immunization but with X85MF1. PMID:17640293

Case-control study on prednisolone combined with ursodeoxycholic acid and azathioprine in pure primary biliary cirrhosis with high levels of immunoglobulin G and transaminases: efficacy and safety analysis.

PubMed

Fang, Yu-Qing; Lv, Dong-Xia; Jia, Wei; Li, Jun; Deng, Yong-Qiong; Wang, Yan; Yu, Min; Wang, Gui-Qiang

2014-10-01

To the best of our knowledge, this is the first study to address the use of glucocorticoids in the comparatively special population of pure primary biliary cirrhosis (PBC) patients who have high levels of immunoglobulin G (IgG) and transaminases but do not have PBC-autoimmune hepatitis overlap syndrome. Ursodeoxycholic acid (UDCA) is now assumed to be the standard therapy for PBC patients. However, patients treated with UDCA still have a risk of progression to cirrhosis and end-stage liver disease. The most recent European Association for the Study of the Liver guidelines of 2009 declared that further studies on glucocorticoid therapy in this disease should be a priority. Therefore, we designed this 3-year longitudinal retrospective study, which might provide deep insight into the treatment for PBC.The aim of this study was to assess whether the combination of prednisolone, UDCA, and azathioprine was superior to UDCA alone in these PBC patients.Sixty patients were enrolled in this study. Thirty-one patients underwent UDCA monotherapy, and 29 patients were treated with prednisolone, UDCA, and azathioprine. We analyzed their biochemistries, immune parameters, liver synthetic function, and noninvasive assessments of liver fibrosis, as well as treatment efficacy and adverse effects at baseline and at 1, 3, 6, 12, 24, and 36 months.Alkaline phosphatase (ALP), γ-glutamyl transpeptidase, alanine aminotransferase, and aspartate aminotransferase levels and the aspartate aminotransferase-to-platelet ratio index (APRI) and S-index improved dramatically in both groups, whereas IgG levels only decreased in the combination group (all P < 0.05). Albumin (ALB) levels decreased in the UDCA group but increased with the combination treatment at 36 months. Significant differences between the 2 groups were observed at 36 months in ALP (P = 0.005), IgG (P = 0.002), ALB (P = 0.002), APRI (P = 0.015), and S-index (P = 0.020). Prednisolone combined with UDCA and azathioprine showed a higher efficacy based on our new criteria.The combination of prednisolone, UDCA, and azathioprine is superior to UDCA alone for the treatment of pure PBC patients with high levels of IgG and transaminases. Side effects were minimal or absent.

Recombinant Newcastle disease virus expressing African swine fever virus protein 72 is safe and immunogenic in mice.

PubMed

Chen, Xinxin; Yang, Jifei; Ji, Yanhong; Okoth, Edward; Liu, Bin; Li, Xiaoyang; Yin, Hong; Zhu, Qiyun

2016-04-01

African swine fever (ASF) is a lethal hemorrhagic disease that affects wild and domestic swine. The etiological agent of ASF is African swine fever virus (ASFV). Since the first case was described in Kenya in 1921, the disease has spread to many other countries. No commercial vaccines are available to prevent ASF. In this study, we generated a recombinant Newcastle disease virus (rNDV) expressing ASFV protein 72 (p72) by reverse genetics and evaluated its humoral and cellular immunogenicity in a mouse model. The recombinant virus, rNDV/p72, replicated well in embryonated chicken eggs and was safe to use in chicks and mice. The p72 gene in rNDV/p72 was stably maintained through ten passages. Mice immunized with rNDV/p72 developed high titers of ASFV p72 specific IgG antibody, and had higher levels of IgG1 than IgG2a. Immunization also elicited T-cell proliferation and secretion of IFN-γ and IL-4. Taken together, these results indicate that rNDV expressing ASFV p72 might be a potential vaccine candidate for preventing ASF.

Seropositivity of Toxoplasma gondii and Toxocara spp. in Children with Cryptogenic Epilepsy, Benha, Egypt.

PubMed

Eraky, Maysa Ahmad; Abdel-Hady, Soha; Abdallah, Karim Fetouh

2016-06-01

The present study aimed to investigate the possible association of Toxoplasma gondii and Toxocara spp. infections with cryptogenic epilepsy in children. The study was carried out between June 2014 and March 2015. Total 90 children (40 with cryptogenic epilepsy, 30 with non-cryptogenic epilepsy, and 20 healthy control children) were evaluated to determine the anti-Toxocara and anti-T. gondii IgG seropositivity using ELISA kits. Epileptic cases were selected from those attending the pediatrics outpatient clinic of Benha University Hospital, Pediatrics Neurology Unit, and from Benha Specialized Hospital of children. The results showed that the level of anti-T. gondii IgG seropositivity was significantly higher among children with cryptogenic epilepsy (20%) than among children with non-cryptogenic children (0%). In healthy controls (10%), there was no association between toxocariasis seropositivity and cryptogenic epilepsy (only 5.7%; 4 out of 70 cases) among cases and 10% (2 out of 20) among controls. Among toxocariasis IgG positive cases, 3 (7.5%) were cryptogenic, and only 1 (3.3%) was non-cryptogenic. These statistically significant results support the association between T. gondii infection and cryptogenic epilepsy while deny this association with toxocariasis.

IgA and IgG1 reactivities assessed by flow cytometry mirror clinical aspects of infants with ocular congenital toxoplasmosis.

PubMed

de Jesus, Laura Néspoli Nassar Pansini; Tonini, Aline de Castro Zacche; Barros, Geisa Baptista; Coelho-dos-Reis, Jordana Grazziela A; Béla, Samantha Ribeiro; Antonelli, Lis Ribeiro do Valle; Machado, Anderson Silva; Carneiro, Ana Carolina Aguiar Vasconcelos; Andrade, Gláucia Manzan Queiroz; Vasconcelos-Santos, Daniel Vitor; Januário, José Nélio; Teixeira-Carvalho, Andréa; Vitor, Ricardo Wagner Almeida; Ferro, Eloísa A V; Mineo, José Roberto; Bahia-Oliveira, Lilian Maria Garcia; Martins-Filho, Olindo Assis; Lemos, Elenice Moreira

2016-01-01

This study intended to apply the flow cytometric analysis of IgA and IgG reactivity and intracytoplasmic cytokine analysis to understand and decode the clinical aspects of infants with ocular congenital toxoplasmosis. The Toxoplasma gondii-infected infants (TOXO) were subdivided according to their clinical aspects based on the absence (NRL), presence of active (ARL), active/cicatricial (ACRL) or cicatricial retinochoroidal lesions (CRL) and compared to non-infected controls (NI). The reactivity of anti-T. gondii IgG subclasses resembles the clinical aspects of ocular lesions. IgG and IgG1 discriminate infants with cicatricial lesions (ACRL and CRL) from both ARL and NLR. IgG2 and IgG3 are particularly higher in ACRL and CRL as compared to NLR. No differences were observed when IgG4 reactivity was evaluated. Thus, the results indicated that the reactivity patterns of IgA, IgG and IgG subclasses are able to discriminate ARL, ACRL and CRL from NLR or NI. IgA and IgG subclasses are relevant serological biomarkers with diagnostic and prognostic applicability, respectively. Moreover, IgA and IgG1 were closely related to cytokine production by innate/adaptive immunity cells. IgA reactivity was directly associated to TNF-α-derived from neutrophils, monocytes and CD8(+) T-cells, while IgG1 was inversely correlated with IFN-γ-producing CD4(+) and CD8(+) T-cells but positively correlated with IL-10(+) B-cells. These findings provide insights on the relationship between the cytokine production by innate/adaptive immunity and the antibody pattern of infants with ocular congenital toxoplasmosis. In addition, the present study supports the use of flow cytometric serology as a potential tool for the diagnosis and monitoring of ocular lesions in T. gondii-infected infants in the clinical setting. Copyright © 2015 Elsevier B.V. All rights reserved.

Detection of Immunoglobulin G Antibodies to Taenia solium Cysticercosis Antigen Glutathione-S-Transferase-rT24H in Malian Children Using Multiplex Bead Assay.

PubMed

Moss, Delynn M; Handali, Sukwan; Chard, Anna N; Trinies, Victoria; Bullard, Stevan; Wiegand, Ryan E; Doumbia, Seydou; Freeman, Matthew C; Lammie, Patrick J

2018-05-01

Blood samples from 805 students attending 42 elementary schools in Mopti, Sikasso, and Koulikoro regions, and Bamako district in Mali participated in a school water, sanitation, and hygiene intervention. Immunoglobulin (Ig) G responses to several antigens/pathogens were assessed by a multiplex bead assay (MBA), and the recombinant Taenia solium T24H antigen was included. Of all students tested, 8.0% were positive to rT24H, but in some schools 25-30%. A cluster of 12 widespread school locations showed not only a relative risk of 3.23 for T. solium exposure and significantly higher IgG responses ( P < 0.001) but also significantly lower elevation ( P = 0.04) (m, above sea level) compared with schools outside the cluster. All schools at elevations < 425 m showed significantly higher IgG responses ( P = 0.017) than schools at elevations ≥ 425 m. The MBA is an excellent serological platform that provides cost-effective opportunities to expand testing in serosurveys.

Clinical and immunological surveys in bee keepers.

PubMed

Bousquet, J; Coulomb, Y; Robinet-Levy, M; Michel, F B

1982-07-01

Two hundred and fifty bee keepers in the South of France, working seasonally, were clinically investigated by means of a questionnaire. Forty-three per cent had presented anaphylactic symptoms and 7.0% toxic reactions when stung by bees. The personal atopic history was found to be significantly (P less than 0.01) elevated in bee keepers who experienced anaphylaxis. Total serum IgE and been venom-specific IgE were titrated in 100 subjects. Total serum IgE was significantly elevated in allergic bee keepers (P = 0.02). Although bee venom-specific IgE were significantly (P less than 0.01) higher in allergic bee keepers this parameter cannot discriminate between allergic and non-allergic bee keepers owing to a considerable overlap. Bee venom-specific IgG was assayed in seventy subjects. Their level was significantly (P less than 0.001) higher in allergic and non-allergic bee keepers as compared with non-allergic blood donors and non-bee-keeping allergic patients. In both bee keeper groups there was no difference in bee venom-specific IgG titres.

Nontuberculous mycobacterial infection with concurrent IgG4-related lymphadenopathy.

PubMed

Liu, Ting-Ting; Weng, Shao-Wen; Wang, Ming-Chung; Huang, Wan-Ting

2016-03-01

Disseminated nontuberculous mycobacteria (NTM) infection with concurrent IgG4-related lymphadenopathy has not been reported. We described a patient with neutralizing autoantibodies to interferon-gamma (IFN-γ) and elevated levels of serum IgG4 presenting with generalized lymphadenopathy and reactive dermatosis. Histologically, lymph nodes (LNs) showed effaced nodal architecture with polymorphic infiltrates, mimicking angioimmunoblastic T-cell lymphoma. Both the absolute number and the ratio of IgG4+ plasma cells to IgG+ plasma cells were increased. Mycobacterium abscessus was isolated from cultures of LNs, and demonstrated by polymerase chain reaction-restriction fragment length polymorphism. The skin biopsy showed neutrophilic dermatosis, consistent with Sweet syndrome. The patient met the criteria of both adult-onset immunodeficiency syndrome and IgG4-related lymphadenopathy. This case provides evidence of disseminated NTM infection with concurrent type III IgG4-related lymphadenopathy in the patient with anti-IFN-γ autoantibodies. © 2015 APMIS. Published by John Wiley & Sons Ltd.

Efficacy of Substance Removal by Immunoadsorption With a Selective Plasma Separator.

PubMed

Hanafusa, Norio; Yamamoto, Hiroko; Tamachi, Masaki; Torato, Toshihiro; Sakurai, Satoko; Tsuchiya, Ken; Nitta, Kosaku; Nangaku, Masaomi

2017-06-01

Immunoadsorption with a tryptophan-conjugated column has a limited capacity and reduces fibrinogen. We speculated that immunoadsorption with a selective plasma separator has higher efficiency in removing immunoglobulins than ordinary immunoadsorption without affecting coagulation factors. This study investigated the efficacy of immunoadsorption with a selective plasma separator in vitro. The sieving coefficients, the pool concentration, and the adsorbed amount were investigated serially with up to 5 L of processed plasma. The sieving coefficients of the selective plasma separator were 0.8, 0.5, and 0.1 for albumin, immunoglobulin G (IgG), and factor 13, respectively. The trend of concentrations for the ordinary plasma separator in the pool reached its nadir at 1.5 L and 3.5 L of plasma processed for IgG, IgG1, or IgG2, and IgG3, respectively. However, the volume was doubled for the selective plasma separator. The trends of fibrinogen and factor 13 concentrations differed significantly between two plasma separators. The trends of the absorbed amount were mirror images of the concentration in the pool. Comparison of the peak amount absorbed indicated that the amounts were almost identical between the two separators for IgG, IgG1, and IgG2. On the other hand, the peak amounts were less for albumin, fibrinogen, and IgG3 with the selective plasma separator than with the ordinary separator. Although further investigations about bradykinin are required, immunoadsorption with the selective plasma separator supports the administration of more frequent and intensive treatments to remove IgG1 or IgG2 without affecting coagulation factors. © 2017 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.

Toxocariasis: critical analysis of serology in patients attending a public referral center for ophthalmology in Brazil.

PubMed

Rubinsky-Elefant, Guita; Yamamoto, Joyce H; Hirata, Carlos E; Prestes-Carneiro, Luiz E

2018-01-01

To analyze the contribution of IgG anti-Toxocara antibodies in the diagnosis of ocular toxocariasis (OT) in serum samples of patients attending a public referral center for ophthalmology in Brazil and to determine the most frequent ocular signs and symptoms. This was a retrospective descriptive study of a cohort of outpatients followed from December 1989 to May 2006. IgG anti-Toxocara antibody titers were determined by enzyme-linked immunosorbent assay. The results were correlated with the clinical and funduscopic findings. Of the diagnoses for the 126 patients, 42 were considered as probable OT, 48 as negative, and 36 as inconclusive. The median IgG anti-Toxocara antibody titers of the patients with probable OT were significantly higher than those of the patients in the negative or inconclusive groups (P = 0.0001). Higher titers were observed more frequently in patients in the probable OT group (P = 0.01) than in the negative group, in which titers were absent or lower in most patients (P < 0.0001). The right eye was affected more in the OT group than in the negative group (P = 0.01), and inflammation was located mostly in the intermediate and posterior poles. The mean age of the patients diagnosed with probable OT was significantly lower (mean, 8 years) than that of the negative patients (mean, 14.5 years) (P = 0.006). Higher levels of antibodies could help with the diagnosis of OT in patients with symptoms and clinical signs; however, negative results cannot exclude possible OT. Conversely, patients with negative serology or low titers make the diagnosis of OT less likely.

High seroprevalence for indigenous spotted fever group rickettsiae in forestry workers from the federal state of Brandenburg, Eastern Germany.

PubMed

Wölfel, Silke; Speck, Stephanie; Essbauer, Sandra; Thoma, Bryan R; Mertens, Marc; Werdermann, Sandra; Niederstrasser, Olaf; Petri, Eckhardt; Ulrich, Rainer G; Wölfel, Roman; Dobler, Gerhard

2017-01-01

In the last decade six Rickettsia species, including Rickettsia slovaca have been characterized in Germany. All of these species could be linked to distinct clinical syndromes in humans. However, due to lack of seroepidemiological data an estimation of the prevalence and the public health impact of rickettsial infections in Germany is difficult. The aim of the present study was to determine the seroprevalence of spotted fever group (SFG) rickettsiae in a population with an elevated exposure risk to ticks. For that purpose, 559 sera of forestry workers in the federal state of Brandenburg, Eastern Germany, were screened for SFG-rickettsiae reactive IgG antibodies. Positive sera were subsequently titrated by microimmunofluorescence assay against R. helvetica, R. raoultii, R. felis, "R. monacensis" and R. slovaca. The total average IgG seroprevalence rate against SFG rickettsiae of 27.5% was found to be represented by 9.7% R. helvetica, 5% R. raoultii, 2.7% R. felis, 0.5% "R. monacensis" and 0.5% R. slovaca. The remaining 9.1% positive test results were of non-differentiable origin. IgG seroprevalences ranged from 11% to 55% in the different forestry districts. Older and male participants had a significantly higher probability for seropositivity and higher anti-rickettsia antibody titer level. In addition, the number of recent as well as the recalled lifetime tick bites was significantly associated with seropositivity and higher titers against SFG rickettsiae. In conclusion, we found an unexpected high total seroprevalence against SFG rickettsiae in forestry workers and serological evidence confirming the occurrence of R. raoultii, R. felis, "R. monacensis" and R. helvetica in the federal State of Brandenburg. Copyright © 2016 Elsevier GmbH. All rights reserved.

Poly(I:C) adjuvant strongly enhances parasite-inhibitory antibodies and Th1 response against Plasmodium falciparum merozoite surface protein-1 (42-kDa fragment) in BALB/c mice.

PubMed

Mehrizi, Akram Abouie; Rezvani, Niloufar; Zakeri, Sedigheh; Gholami, Atefeh; Babaeekhou, Laleh

2018-04-01

Malaria vaccine development has been confronted with various challenges such as poor immunogenicity of malaria vaccine candidate antigens, which is considered as the main challenge. However, this problem can be managed using appropriate formulations of antigens and adjuvants. Poly(I:C) is a potent Th1 inducer and a human compatible adjuvant capable of stimulating both B- and T-cell immunity. Plasmodium falciparum merozoite surface protein 1 42 (PfMSP-1 42 ) is a promising vaccine candidate for blood stage of malaria that has faced several difficulties in clinical trials, mainly due to improper adjuvants. Therefore, in the current study, poly(I:C), as a potent Th1 inducer adjuvant, was evaluated to improve the immunogenicity of recombinant PfMSP-1 42 , when compared to CFA/IFA, as reference adjuvant. Poly(I:C) produced high level and titers of anti-PfMSP-1 42 IgG antibodies in which was comparable to CFA/IFA adjuvant. In addition, PfMSP-1 42 formulated with poly(I:C) elicited a higher ratio of IFN-γ/IL-4 (23.9) and IgG2a/IgG1 (3.77) with more persistent, higher avidity, and titer of IgG2a relative to CFA/IFA, indicating a potent Th1 immune response. Poly(I:C) could also help to induce anti-PfMSP-1 42 antibodies with higher growth-inhibitory activity than CFA/IFA. Altogether, the results of the current study demonstrated that poly(I:C) is a potent adjuvant that can be appropriate for being used in PfMSP-1 42 -based vaccine formulations.

Sensitive assays enable detection of serum IgG antibodies against Clostridium difficile toxin A and toxin B in healthy subjects and patients with Clostridium difficile infection.

PubMed

Zhao, Xuemei; Bender, Florent; Shukla, Rajiv; Kang, John J; Caro-Aguilar, Ivette; Laterza, Omar F

2016-04-01

Pathogenic Clostridium difficile produces two proinflammatory exotoxins, toxin A and toxin B. Low level of serum antitoxin IgG antibodies is a risk factor for the development of primary and recurrent C. difficile infection (CDI). We developed and validated two sensitive, titer-based electrochemiluminescence assays for the detection of serum antibody levels against C. difficile toxins A and B. These assays demonstrated excellent precision. The sensitivity of the assays allowed the detection of antitoxin A and antitoxin B IgG antibodies in all tested serum samples during assay validation. The validated titer-based assays enable assessment of antitoxin A and antitoxin B IgG antibodies as potential biomarkers to identify patients with CDI at increased risk for CDI recurrence.

Chemical modification of protein A chromatography ligands with polyethylene glycol. I: Effects on IgG adsorption equilibrium, kinetics, and transport.

PubMed

Weinberg, Justin; Zhang, Shaojie; Crews, Gillian; Carta, Giorgio; Przybycien, Todd

2018-04-20

Chemical modification of Protein A (ProA) chromatography ligands with polyethylene glycol (PEGylation) has been proposed as a strategy to increase the process selectivity and resin robustness by providing the ligand with a steric repulsion barrier against non-specific binding. This article comprises a comprehensive study of IgG adsorption and transport in Repligen CaptivA PriMAB resin with PEGylated ProA ligands that are modified using 5.2 and 21.5 kDa PEG chains. We studied the impact of the molecular weight of the PEG as well as the extent of PEGylation for the 5.2 kDa PEG modification. In all cases, PEGylation of ProA ligands decreases the resin average pore size, particle porosity, and static binding capacity for IgG proportional to the volume of conjugated PEG in the resin. Resin batch uptake experiments conducted in bulk via a stirred-tank system and with individual resin particles under confocal laser scanning microscopy suggests that PEGylation introduces heterogeneity into IgG binding kinetics: a fraction of the IgG binding sites are transformed from typical fast association kinetic behavior to slow kinetic behavior. pH gradient elution experiments of an IgG molecule on the modified resins show an increase in IgG elution pH for all modified resins, implying a decrease in IgG-ProA binding affinity on modification. Despite losses in static binding capacity for all resins with PEGylated ligands, the loss of dynamic binding capacity at 10% breakthrough (DBC 10% ) ranged more broadly from almost 0-47% depending on the PEG molecular weight and the extent of PEGylation. Minimal losses in DBC 10% were observed with a low extent of PEGylation with a smaller molecular weight PEG, while higher losses were observed at higher extents of PEGylation and with higher molecular weight PEG due to decreased static binding capacity and increased mass transfer resistance. This work provides insight into the practical implications for resin performance if PEGylation is considered as a strategy for selectivity enhancement in affinity chromatography with macromolecular ligands. Copyright © 2018 Elsevier B.V. All rights reserved.