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Sample records for aloinmune neonatal igg

  1. Albumin quotient, IgG concentration, and IgG index determinations in cerebrospinal fluid of neonatal foals.

    PubMed

    Andrews, F M; Geiser, D R; Sommardahl, C S; Green, E M; Provenza, M

    1994-06-01

    Total protein (TP), albumin, and IgG concentrations were measured in CSF from the atlanto-occipital (AO) and lumbosacral (LS) sites and in serum of 15 clinically normal neonatal foals < or = 10 days old (mean, 7.0 days). The albumin quotient (AQ; CSF albumin/serum albumin x 100) and IgG index ([CSF IgG/serum IgG] x [serum albumin/CSF albumin]), indicators of blood-brain barrier permeability and intrathecal IgG production, respectively, were then calculated. Mean +/- SD values obtained from the foals of this study were: serum albumin, 2,900 +/- 240 mg/dl; serum IgG, 1,325 +/- 686 mg/dl; AO CSF total protein (TP), 82.8 +/- 19.2 mg/dl; LS CSF TP, 83.6 +/- 16.1 mg/dl; AO CSF albumin, 52.0 +/- 8.6 mg/dl; LS CSF albumin, 53.8 +/- 15.7 mg/dl; AO CSF IgG, 10.2 +/- 5.5 mg/dl; LS CSF IgG, 9.9 +/- 5.7 mg/dl; AO AQ, 1.86 +/- 0.29; LS AQ, 1.85 +/- 0.51, AO IgG index, 0.52 +/- 0.28; and LS IgG index, 0.48 +/- 0.27. Significant difference between values for the AO and LS sites was not found. A CSF albumin concentration > 85.2 mg/dl or AQ > 2.4, as determined by mean +/- 2 SD, may indicate increased blood-brain barrier permeability. An IgG index value > 1.0 may indicate intrathecal IgG production. Values obtained for foals of this study should serve as baseline for comparison in the evaluation of blood-brain barrier permeability and intrathecal IgG production in neonatal foals with neurologic disease. PMID:7944008

  2. IgG transport across mucosal barriers by neonatal Fc receptor for IgG and mucosal immunity.

    PubMed

    Yoshida, Masaru; Masuda, Atsuhiro; Kuo, Timothy T; Kobayashi, Kanna; Claypool, Steven M; Takagawa, Tetsuya; Kutsumi, Hiromu; Azuma, Takeshi; Lencer, Wayne I; Blumberg, Richard S

    2006-12-01

    Mucosal secretions of the human gastrointestinal, respiratory, and genital tracts contain significant quantities of IgG. The neonatal Fc receptor for IgG (FcRn) plays a major role in regulating host IgG levels and transporting IgG and associated antigens across polarized epithelial barriers. The FcRn can then recycle the IgG/antigen complex back across the intestinal barrier into the lamina propria for processing by dendritic cells and presentation to CD4(+) T cells in regional organized lymphoid structures. FcRn, through its ability to secrete and absorb IgG, thus integrates luminal antigen encounters with systemic immune compartments and, as such, provides essential host defense and immunoregulatory functions at the mucosal surfaces. PMID:17051393

  3. Characterization and screening of IgG binding to the neonatal Fc receptor.

    PubMed

    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

  4. In utero sensitization modulates IgG isotype, IFN-γ and IL-10 responses of neonates in bancroftian filariasis.

    PubMed

    Achary, K G; Mandal, N N; Mishra, S; Mishra, R; Sarangi, S S; Satapathy, A K; Kar, S K; Bal, M S

    2014-10-01

    In utero exposure has been considered as a risk factor for filarial infection. To evaluate the influence of maternal infection on filarial-specific IgG subclass response in neonates and their correlation with plasma levels IL-10 and interferon-γ, 145 pairs of mothers and their respective cord bloods were examined. Transplacental transfer of circulating filarial antigen (CFA) was observed in 34·8% cord bloods from CFA positive mothers. Filarial-specific IgG1, IgG2 and IgG4 responses of cord bloods were found to be positively correlated with CFA of mothers. In contrast, IgG3 responses negatively correlated with CFA of mothers. The % of similarity of recognition pattern in the cord blood with maternal blood was high for IgG3 response than IgG4 in all three groups. An increased levels of IL-10 and decreased levels of interferon gamma (IFN-γ) were observed in cord blood of infected mothers. Interferon gamma was positively correlated with IgG3 and negatively correlated with IgG4 level. On the other hand, IL-10 was positively correlated with IgG4 and CFA, indicating that cytokines may play a role in modulating the immune responses in cord bloods of sensitized foetus. The findings of the study reveal that in utero tolerance or sensitization may influence the filarial-specific immunity to infection in neonates. PMID:24902619

  5. Neonatal Fc Receptor-Mediated IgG Transport Across Porcine Intestinal Epithelial Cells: Potentially Provide the Mucosal Protection.

    PubMed

    Guo, Jinyue; Li, Fei; He, Qigai; Jin, Hui; Liu, Mei; Li, Shaowen; Hu, Sishun; Xiao, Yuncai; Bi, Dingren; Li, Zili

    2016-06-01

    It has been well characterized that piglets can absorb colostrum IgG across the intestine to neonatal bloodstream and a certain level of IgG has been found in the mucosal secretions of the porcine intestinal tract. However, little is known about how the maternal IgG transport across the intestinal barrier and how IgG enter the lumen of intestinal tract. In this study, we demonstrated that the porcine neonatal Fc receptor (pFcRn) was expressed in a model of normal porcine intestinal epithelial cells (IPEC-J2) as well as in kidney cells (PK-15), and pFcRn was mainly distributed in the apical side of the polarized IPEC-J2 cells. Analyzing the phylogenetic relatedness of this gene we found that swine and human neonatal Fc receptor (FcRn) amino acid sequence are closer than rodents. We also showed that pFcRn mediated bidirectional IgG transport across polarized IPEC-J2 cells and bound to IgG in a pH-dependent manner. Furthermore, pFcRn-transcytosed viral-specific IgG reduced the transmissible gastroenteritis virus (TGEV) yield from the luminal direction by a 50% tissue culture infective dose (TCID50) assay. Our results indicate that pFcRn-dependent bidirectional IgG transport across the intestinal epithelium plays critical role in the acquisition of humoral immunity in early life and in host defense at mucosal surfaces. PMID:26982157

  6. Identification and characterization of a novel splicing variant of the MHC classI-related Neonatal Fc receptor for IgG

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The neonatal Fc receptor for IgG (FcRn), a MHC class I-related molecule, functions to transport maternal IgG into the fetus or newborn via placenta and/or intestine and protects IgG from catabolism. The mRNAs of several MHC class I-related molecules have multiple splicing variants. In the course of ...

  7. Identification and characterization of a novel splicing variant of the MHC class 1-related neonatal Fe receptor for IgG.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The neonatal Fc receptor for IgG (FcRn), a MHC class I-related molecule, functions to transport maternal IgG to the fetus or newborn via placenta or intestine and protects IgG from catabolism. In the course of cloning porcine FcRn from the intestinal epithelial cell line IPEC, two cDNAs were identif...

  8. Impact of IgG2 high molecular weight species on neonatal Fc receptor binding assays.

    PubMed

    Zhang, Yuling; Mathur, Abhishek; Maher, Gwen; Arroll, Thomas; Bailey, Robert

    2015-11-15

    A cell-based assay and a solution neonatal Fc receptor (FcRn) binding assay were implemented for the characterization of an IgG2 antibody after observation that different product lots exhibited unexpected differences in FcRn binding in the cell-based format with membrane-bound FcRn. The experiments described here suggest that the apparent differences observed in the FcRn binding across different product lots in the cell-based format can be attributed to the different levels of the higher order high molecular weight species (HMWs) in them. A strong correlation between FcRn binding in the cell-based format and the percentage (%) higher order HMWs suggests that small amounts (∼0.1%) of the latter could cause the enhanced apparent FcRn binding (% relative binding ranging from 50 to 100%) in the format. However, when the binding was assessed with recombinant FcRn in soluble form, avidity effects were minimal and the assay format exhibited less sensitivity toward the differences in higher order HMWs levels across product lots. In conclusion, a solution-based assay may be a more appropriate assay to assess FcRn binding of the dominant species of an Fc-fusion protein or monoclonal antibody if minor differences in product variants such as higher order HMWs are shown to affect the binding significantly. PMID:26255698

  9. A novel in vitro assay to predict neonatal Fc receptor-mediated human IgG half-life.

    PubMed

    Souders, Colby A; Nelson, Stuart C; Wang, Yang; Crowley, Andrew R; Klempner, Mark S; Thomas, William

    2015-01-01

    Immunoglobulin G (IgG) has an unusually long serum half-life in comparison to proteins of a similar size. It is well-known that this phenomenon is due to IgG's ability to bind the neonatal Fc receptor (FcRn) in a pH-dependent manner. FcRn binding properties can vary among IgGs, resulting in altered in vivo half-lives, and therefore it would be beneficial to accurately predict the FcRn binding properties of therapeutic IgG monoclonal antibodies (mAbs). Here we describe the development of an in vitro model capable of predicting the in vivo half-life of human IgG. Using a high-throughput biolayer interferometry (BLI) platform, the human FcRn association rate at acidic pH and subsequent dissociation rate at physiological pH was determined for 5 human IgG1 mAbs. Comparing the combined FcRn association and dissociation rates to the Phase 1 clinical study half-lives of the mAbs resulted in a strong correlation. The correlation was also verified in vivo using mice transgenic for human FcRn. The model was used to characterize various factors that may influence FcRn-mAb binding, including mAb variable region sequence differences and constant region glycosylation patterns. Results indicated that the complementarity-determining regions of the heavy chain significantly influence the mAb's FcRn binding properties, while the absence of glycosylation does not alter mAb-FcRn binding. Development of this high-throughput FcRn binding model could potentially predict the half-life of therapeutic IgGs and aid in selection of lead candidates while also serving as a screening tool for the development of mAbs with desired pharmacokinetic properties. PMID:26018774

  10. Fully human monoclonal antibody inhibitors of the neonatal fc receptor reduce circulating IgG in non-human primates.

    PubMed

    Nixon, Andrew E; Chen, Jie; Sexton, Daniel J; Muruganandam, Arumugam; Bitonti, Alan J; Dumont, Jennifer; Viswanathan, Malini; Martik, Diana; Wassaf, Dina; Mezo, Adam; Wood, Clive R; Biedenkapp, Joseph C; TenHoor, Chris

    2015-01-01

    The therapeutic management of antibody-mediated autoimmune disease typically involves immunosuppressant and immunomodulatory strategies. However, perturbing the fundamental role of the neonatal Fc receptor (FcRn) in salvaging IgG from lysosomal degradation provides a novel approach - depleting the body of pathogenic immunoglobulin by preventing IgG binding to FcRn and thereby increasing the rate of IgG catabolism. Herein, we describe the discovery and preclinical evaluation of fully human monoclonal IgG antibody inhibitors of FcRn. Using phage display, we identified several potent inhibitors of human-FcRn in which binding to FcRn is pH-independent, with over 1000-fold higher affinity for human-FcRn than human IgG-Fc at pH 7.4. FcRn antagonism in vivo using a human-FcRn knock-in transgenic mouse model caused enhanced catabolism of exogenously administered human IgG. In non-human primates, we observed reductions in endogenous circulating IgG of >60% with no changes in albumin, IgM, or IgA. FcRn antagonism did not disrupt the ability of non-human primates to mount IgM/IgG primary and secondary immune responses. Interestingly, the therapeutic anti-FcRn antibodies had a short serum half-life but caused a prolonged reduction in IgG levels. This may be explained by the high affinity of the antibodies to FcRn at both acidic and neutral pH. These results provide important preclinical proof of concept data in support of FcRn antagonism as a novel approach to the treatment of antibody-mediated autoimmune diseases. PMID:25954273

  11. A novel in vitro assay to predict neonatal Fc receptor-mediated human IgG half-life

    PubMed Central

    Souders, Colby A; Nelson, Stuart C; Wang, Yang; Crowley, Andrew R; Klempner, Mark S; Thomas, William

    2015-01-01

    Immunoglobulin G (IgG) has an unusually long serum half-life in comparison to proteins of a similar size. It is well-known that this phenomenon is due to IgG's ability to bind the neonatal Fc receptor (FcRn) in a pH-dependent manner. FcRn binding properties can vary among IgGs, resulting in altered in vivo half-lives, and therefore it would be beneficial to accurately predict the FcRn binding properties of therapeutic IgG monoclonal antibodies (mAbs). Here we describe the development of an in vitro model capable of predicting the in vivo half-life of human IgG. Using a high-throughput biolayer interferometry (BLI) platform, the human FcRn association rate at acidic pH and subsequent dissociation rate at physiological pH was determined for 5 human IgG1 mAbs. Comparing the combined FcRn association and dissociation rates to the Phase 1 clinical study half-lives of the mAbs resulted in a strong correlation. The correlation was also verified in vivo using mice transgenic for human FcRn. The model was used to characterize various factors that may influence FcRn-mAb binding, including mAb variable region sequence differences and constant region glycosylation patterns. Results indicated that the complementarity-determining regions of the heavy chain significantly influence the mAb's FcRn binding properties, while the absence of glycosylation does not alter mAb-FcRn binding. Development of this high-throughput FcRn binding model could potentially predict the half-life of therapeutic IgGs and aid in selection of lead candidates while also serving as a screening tool for the development of mAbs with desired pharmacokinetic properties. PMID:26018774

  12. ASSOCIATION OF BOVINE NEONATAL FC RECEPTOR GENE (FCGRT) HAPLOTYPES WITH SERUM IGG CONCENTRATION IN NEWBORN CALVES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Calves are born with little or no circulating immunoglobulin. Within 24 hours after birth, calves acquire immunoglobulins through passive transfer from ingestion of maternal colostrum. When this process fails, calves are at high risk for postnatal infections. Uptake of IgG from the intestinal lum...

  13. [Autoimmune-alloimmune neonatal neutropenia. Serum reactive IgG and neutrophil-specific phenotype detected by flow cytometry].

    PubMed

    Riera, Norma E; Kantor, Gustavo L; Khoury, Marina; Nucci, Rodrigo Parias; Rapetti, Maria Cristina; Aixala, Monica; Goldsztein, Sofia; Flores, Gabriela; de Bracco, Maria M de E

    2006-01-01

    Auto or alloantibodies reactive with neutrophils define immune neutropenia. Alloimmune neonatal neutropenia is caused by maternal sensitization to paternal neutrophil antigens, resulting in IgG antibodies that are transferred to the fetus through the placenta. We present the studies in 4 children from 3 families with neutropenia of unknown origin (two of them were brothers). They were evaluated by flow cytometry in parallel with leukoagglutination. Reference values were established for serum reactive IgG in healthy volunteers for three dilutions (1/2, 1/5 and 1/20), both for the autologous reaction (serum and cells of the same individual) and for the heterologous reaction (serum and cells of different individuals). Results were expressed by an index defined by the quotient of the mean fluorescence intensity of the patient's serum divided by that of the reference serum. Serum reactive/agglutinant factors and circulating immune complexes were evaluated in patients and parents serum. Neutrophil specific phenotypes were determined for HNA-1a, HNA-1b and HNA-2a. Reactive IgG/agglutinant factors were found in 4 children. Two maternal sera were reactive against paternal and/or children neutrophils. Circulating immune complexes were detected in 2/4 children sera and were negative in 3/3 maternal sera. Maternal/children incompatibility was detected in the four cases. The three mothers had the same phenotype: homozygous NA1/NA1, NB1+. PMID:17137169

  14. Preterm and term neonates transplacentally acquire IgG antibodies specific to LPS from Klebsiella pneumoniae, Escherichia coli and Pseudomonas aeruginosa.

    PubMed

    Silveira Lessa, Ana Lúcia; Krebs, Vera Lúcia Jornada; Brasil, Tatiana Braga; Pontes, Gerlândia Neres; Carneiro-Sampaio, Magda; Palmeira, Patricia

    2011-07-01

    High incidences of Gram-negative bacteria are found in neonatal nosocomial infections. Our aim was to investigate placental transmission of immunoglobulin G (IgG) reactive with lipopolysaccharide from Klebsiella pneumoniae, Pseudomonas aeruginosa and Escherichia coli O111, O6 and O26. The total and lipopolysaccharide-specific IgM and IgG were determined in 11 maternal/umbilical-cord sera aged ≤33 weeks (GI); 21 aged >33 and <37 weeks (GII); and 32 term newborns (GIII). The total and lipopolysaccharide-specific IgM concentrations were equivalent in maternal sera. The total IgG concentrations were equivalent in maternal and newborn sera, with the exception of GIII newborns as compared with their mothers (P<0.0001) and with neonates from GI and GII (P<0.05). Lipopolysaccharide-specific IgG concentrations were lower in GI neonates than in their mothers (P<0.01) and lower in GII (P<0.05). Lower lipopolysaccharide-specific IgG levels were observed among neonates only for O111 in GI (P<0.05) and for O26 and Pseudomonas in GII, both as compared with GIII (P<0.05). The anti-lipopolysaccharide IgG transfer ratios were lower in GI (except for O26) and in GII (except for Klebsiella and O111) as compared with GIII (P<0.05). Our results suggest that the greater susceptibility to infections in preterm infants is influenced (besides the humoral response) by factors intrinsic and extrinsic to the condition of prematurity. PMID:21481015

  15. Transfer of IgG in the female genital tract by MHC class I-related neonatal Fc receptor (FcRn) confers protective immunity to vaginal infection

    PubMed Central

    Palaniyandi, Senthilkumar; Zeng, Rongyu; Tuo, Wenbin; Roopenian, Derry C.; Zhu, Xiaoping

    2011-01-01

    IgG is a major Ig subclass in mucosal secretions of the human female genital tract, where it predominates over the IgA isotype. Despite the abundance of IgG, surprisingly little is known about where and how IgG enters the lumen of the genital tract and the exact role local IgG plays in preventing sexually transmitted diseases. We demonstrate here that the neonatal Fc receptor, FcRn, is expressed in female genital tract epithelial cells of humans and mice and binds IgG in a pH-dependent manner. In vitro we show that FcRn mediates bidirectional IgG transport across polarized human endometrial HEC-1-A monolayers and primary human genital epithelial cells. Furthermore, endosomal acidification appears to be a prerequisite for FcRn-mediated IgG transcytosis; IgG transcytosis was demonstrated in vivo by translocation of systemically administered IgG into the genital lumen in WT but not FcRn-KO mice. The biological relevance of FcRn-transported IgG was demonstrated by passive immunization using herpes simplex virus-2 (HSV-2)–specific polyclonal serum, which conferred significantly higher protection against intravaginal challenge infection by the HSV-2 186 strain in WT mice than in FcRn-KO mice. These studies demonstrate that FcRn-mediated transport is a mechanism by which IgG can act locally in the female genital tract in immune surveillance and in host defense against sexually transmitted diseases. PMID:21368166

  16. Prevalence of anti-rubella, anti-measles and anti-mumps IgG antibodies in neonates and pregnant women in Catalonia (Spain) in 2013: susceptibility to measles increased from 2003 to 2013.

    PubMed

    Plans, P; de Ory, F; Campins, M; Álvarez, E; Payà, T; Guisasola, E; Compte, C; Vellbé, K; Sánchez, C; Lozano, M J; Aran, I; Bonmatí, A; Carreras, R; Jané, M; Cabero, L

    2015-06-01

    Non-immune neonates and non-immune pregnant women are at risk of developing rubella, measles and mumps infections, including congenital rubella syndrome. We describe the seroepidemiology of measles, mumps and rubella (MMR) in neonates and pregnant women in Catalonia (Spain). Anti-rubella, anti-measles and anti-mumps serum IgG titres were assessed using enzyme-linked immunosorbent assay (ELISA) tests in 353 cord blood samples from neonates of a representative sample of pregnant women obtained in 2013. The prevalence of protective antibody titres in neonates was 96 % for rubella IgG (≥8 IU/ml), 90 % for measles IgG (>300 IU/ml) and 84 % for mumps IgG (>460 EU/ml). Slightly lower prevalences of protective IgG titres, as estimated from the cord blood titres, were found in pregnant women: 95 % for rubella IgG, 89 % for measles IgG and 81 % for mumps IgG. The anti-measles and anti-mumps IgG titres and the prevalences of protective IgG titres against measles and mumps increased significantly (p < 0.001) with maternal age. The prevalence of protective anti-measles IgG titres decreased by 7 % [odds ratio (OR) = 0.15, p < 0.001), the prevalence of protective anti-rubella IgG titres increased by 3 % (OR = 1.80, p < 0.05) and the MMR vaccination coverage (during childhood) in pregnant women increased by 54 % (OR = 2.09, p < 0.001) from 2003 to 2013. We recommend to develop an MMR prevention programme in women of childbearing age based on mass MMR vaccination or MMR screening and vaccination of susceptible women to increase immunity levels against MMR. PMID:25666082

  17. The neonatal Fc receptor (FcRn) binds independently to both sites of the IgG homodimer with identical affinity

    PubMed Central

    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. PMID:25658443

  18. MHC Class I-Related Neonatal Fc Receptor for IgG Is Functionally Expressed in Monocytes, Intestinal Macrophages, and Dendritic Cells1

    PubMed Central

    Zhu, Xiaoping; Meng, Gang; Dickinson, Bonny L.; Li, Xiaotong; Mizoguchi, Emiko; Miao, Lili; Wang, Yuansheng; Robert, Caroline; Wu, Benyan; Smith, Phillip D.; Lencer, Wayne I.; Blumberg, Richard S.

    2010-01-01

    The neonatal Fc receptor (FcRn) for IgG, an MHC class I-related molecule, functions to transport IgG across polarized epithelial cells and protect IgG from degradation. However, little is known about whether FcRn is functionally expressed in immune cells. We show here that FcRn mRNA was identifiable in human monocytes, macrophages, and dendritic cells. FcRn heavy chain was detectable as a 45-kDa protein in monocytic U937 and THP-1 cells and in purified human intestinal macrophages, peripheral blood monocytes, and dendritic cells by Western blot analysis. FcRn colocalized in vivo with macrosialin (CD68) and Ncl-Macro, two macrophage markers, in the lamina propria of human small intestine. The heavy chain of FcRn was associated with the β2-microglobulin (β2m) light chain in U937 and THP-1 cells. FcRn bound human IgG at pH 6.0, but not at pH 7.5. This binding could be inhibited by human IgG Fc, but not Fab. FcRn could be detected on the cell surface of activated, but not resting, THP-1 cells. Furthermore, FcRn was uniformly present intracellularly in all blood monocytes and intestinal macrophages. FcRn was detectable on the cell surface of a significant fraction of monocytes at lower levels and on a small subset of tissue macrophages that expressed high levels of FcRn on the cell surface. These data show that FcRn is functionally expressed and its cellular distribution is regulated in monocytes, macrophages, and dendritic cells, suggesting that it may confer novel IgG binding functions upon these cell types relative to typical FcγRs: FcγRI, FcγRII, and FcγRIII. PMID:11207281

  19. Effect of birthweight, total protein, serum IgG and packed cell volume on risk of neonatal diarrhea in calves on two California dairies.

    PubMed

    Paré, J; Thurmond, M C; Gardner, I A; Picanso, J P

    1993-10-01

    The objective of the study was to determine if there was a relationship between hematological, immunological and physiological variables of newborn calves and risk of diarrhea during the neonatal period. Four hundred and seventeen heifer calves from two dairies (A and B) in the San Joaquin Valley of California were enrolled at birth and scored daily, to 28 days of age, for evidence and severity of diarrhea (0 to 3). Calves were weighted at birth and blood sampled at two to five days of age to determine packed cell volume (PCV), total protein (TP) and IgG serum concentration. The Cox proportional hazards model was used to determine if age at onset of the first diarrhea episode and length of the first episode were associated with the hypothesized variables (PCV, TP, IgG and birthweight). The IgG concentration was not associated with the age at onset of diarrhea (p = 0.6052, Dairy A; p = 0.4393, Dairy B) but a high IgG concentration was associated with a decreased length of episode (p = 0.0325, Dairy A; p = 0.0912, Dairy B), particularly for calves born in the winter on dairy A (p = 0.0211). For calves born in the winter, those with either a high or a low birthweight had diarrhea at a younger age (p = 0.0102, Dairy A; p = 0.0020, Dairy B). Associations were also found for PCV and TP with both the age at onset and length of the first episode of diarrhea. Results suggest that parameters measurable at, or shortly after birth may have important prognostic value in evaluating risk of calf diarrhea. PMID:8269362

  20. Cross-species analysis of Fc engineered anti-Lewis-Y human IgG1 variants in human neonatal receptor transgenic mice reveal importance of S254 and Y436 in binding human neonatal Fc receptor.

    PubMed

    Burvenich, Ingrid J G; Farrugia, William; Lee, Fook T; Catimel, Bruno; Liu, Zhanqi; Makris, Dahna; Cao, Diana; O'Keefe, Graeme J; Brechbiel, Martin W; King, Dylan; Spirkoska, Violeta; Allan, Laura C; Ramsland, Paul A; Scott, Andrew M

    2016-01-01

    IgG has a long half-life through engagement of its Fc region with the neonatal Fc receptor (FcRn). The FcRn binding site on IgG1 has been shown to contain I253 and H310 in the CH2 domain and H435 in the CH3 domain. Altering the half-life of IgG has been pursued with the aim to prolong or reduce the half-life of therapeutic IgGs. More recent studies have shown that IgGs bind differently to mouse and human FcRn. In this study we characterize a set of hu3S193 IgG1 variants with mutations in the FcRn binding site. A double mutation in the binding site is necessary to abrogate binding to murine FcRn, whereas a single mutation in the FcRn binding site is sufficient to no longer detect binding to human FcRn and create hu3S193 IgG1 variants with a half-life similar to previously studied hu3S193 F(ab')2 (t1/2β, I253A, 12.23 h; H310A, 12.94; H435A, 12.57; F(ab')2, 12.6 h). Alanine substitutions in S254 in the CH2 domain and Y436 in the CH3 domain showed reduced binding in vitro to human FcRn and reduced elimination half-lives in huFcRn transgenic mice (t1/2β, S254A, 37.43 h; Y436A, 39.53 h; wild-type, 83.15 h). These variants had minimal effect on half-life in BALB/c nu/nu mice (t1/2β, S254A, 119.9 h; Y436A, 162.1 h; wild-type, 163.1 h). These results provide insight into the interaction of human Fc by human FcRn, and are important for antibody-based therapeutics with optimal pharmacokinetics for payload strategies used in the clinic. PMID:27030023

  1. Transfer of IgG in the female genital tract by MHC class I-related neonatal Fc receptor (FcRn) confers protective immunity to vaginal infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    IgG is a major immunoglobulin subclass in mucosal secretions of human female genital tract, where it predominates over the IgA isotype. Despite the abundance of IgG, surprisingly little is known about whether and how IgG enters the lumen of the genital tract and the exact role of local IgG may play ...

  2. Mechanism-Based Competitive Binding Model to Investigate the Effect of Neonatal Fc Receptor Binding Affinity on the Pharmacokinetic of Humanized Anti-VEGF Monoclonal IgG1 Antibody in Cynomolgus Monkey.

    PubMed

    Ng, Chee M; Fielder, Paul J; Jin, Jin; Deng, Rong

    2016-07-01

    The quantitative relationship between neonatal Fc receptor (FcRn) binding affinity at both acidic and physiological pH and the pharmacokinetics of protein engineered FcRn IgG1 variants has not yet been reported. Our objective was to develop a quantitatively mechanism-based competitive binding model to describe the effects of FcRn binding affinity at acidic and physiological pH on the pharmacokinetics of anti-VEGF IgG1 antibodies when both endogenous and exogenous antibodies are competing for the same FcRn. Pharmacokinetic (PK) and FcRn binding data from five Fc variants of humanized anti-VEGF IgG1 monoclonal antibodies with wide range of FcRn binding affinity were used for the analysis. Sixty-seven anti-VEGF IgG1 antibody-treated animals and 25 control animals with simulated endogenous IgG levels were used to develop the final model. A hybrid iterative two stages and Monte Carlo parametric expectation-maximization method was used to obtain the final model parameters estimates. The final model well described the observed PK data. Quantitative FcRn binding affinity-pharmacokinetics relationships was constructed to provide important biological insights in better understanding of the FcRn binding effect on pharmacokinetics of anti-VEGF IgG1 antibodies in cynomolgus monkeys and served as an important model-based drug discovery platform to guide the design and development of the future generation of anti-VEGF or other therapeutic IgG1 antibodies. PMID:27075465

  3. Mass Spectrometry Detection of G3m and IGHG3 Alleles and Follow-Up of Differential Mother and Neonate IgG3

    PubMed Central

    Dechavanne, Célia; Guillonneau, François; Chiappetta, Giovanni; Sago, Laïla; Lévy, Prisca; Salnot, Virginie; Guitard, Evelyne; Ehrenmann, François; Broussard, Cédric; Chafey, Philippe; Le Port, Agnès; Vinh, Joëlle; Mayeux, Patrick; Dugoujon, Jean-Michel; Lefranc, Marie-Paule; Migot-Nabias, Florence

    2012-01-01

    Mass spectrometry (MS) analysis for detection of immunoglobulins (IG) of the human IgG3 subclass is described that relies on polymorphic amino acids of the heavy gamma3 chains. IgG3 is the most polymorphic human IgG subclass with thirteen G3m allotypes located on the constant CH2 and CH3 domains of the gamma3 chain, the combination of which leads to six major G3m alleles. Amino acid changes resulting of extensive sequencing previously led to the definition of 19 IGHG3 alleles that have been correlated to the G3m alleles. As a proof of concept, MS proteotypic peptides were defined which encompass discriminatory amino acids for the identification of the G3m and IGHG3 alleles. Plasma samples originating from ten individuals either homozygous or heterozygous for different G3m alleles, and including one mother and her baby (drawn sequentially from birth to 9 months of age), were analyzed. Total IgG3 were purified using affinity chromatography and then digested by a combination of AspN and trypsin proteases, and peptides of interest were detected by mass spectrometry. The sensitivity of the method was assessed by mixing variable amounts of two plasma samples bearing distinct G3m allotypes. A label-free approach using the high-performance liquid chromatography (HPLC) retention time of peptides and their MS mass analyzer peak intensity gave semi-quantitative information. Quantification was realized by selected reaction monitoring (SRM) using synthetic peptides as internal standards. The possibility offered by this new methodology to detect and quantify neo-synthesized IgG in newborns will improve knowledge on the first acquisition of antibodies in infants and constitutes a promising diagnostic tool for vertically-transmitted diseases. PMID:23049948

  4. Activation of the JAK/STAT-1 Signaling Pathway by IFN-γ Can Down-Regulate Functional Expression of the MHC Class I-Related Neonatal Fc Receptor for IgG1

    PubMed Central

    Liu, Xindong; Ye, Lilin; Bai, Yu; Mojidi, Habi; Simister, Neil E.; Zhu, Xiaoping

    2009-01-01

    Expression of many MHC genes is enhanced at the transcriptional or posttranscriptional level following exposure to the cytokine IFN-γ. However, in this study we found that IFN-γ down-regulated the constitutive expression of the neonatal Fc receptor (FcRn), an MHC class I-related molecule that functions to transport maternal IgG and protect IgG and albumin from degradation. Epithelial cell, macrophage-like THP-1 cell, and freshly isolated human PBMC exposure to IFN-γ resulted in a significant decrease of FcRn expression as assessed by real-time RT-PCR and Western blotting. The down-regulation of FcRn was not caused by apoptosis or the instability of FcRn mRNA. Chromatin immunoprecipitation and gel mobility shift assays showed that STAT-1 bound to an IFN-γ activation site in the human FcRn promoter region. Luciferase expression from an FcRn promoter-luciferase reporter gene construct was not altered in JAK1- and STAT-1-deficient cells following exposure to IFN-γ, whereas expression of JAK1 or STAT-1 protein restored the IFN-γ inhibitory effect on luciferase activity. The repressive effect of IFN-γ on the FcRn promoter was selectively reversed or blocked by mutations of the core nucleotides in the IFN-γ activation site sequence and by over-expression of the STAT-1 inhibitor PIAS1 or the dominant negative phospho-STAT-1 mutations at Tyr-701 and/or Ser-727 residues. Furthermore, STAT-1 might down-regulate FcRn transcription through sequestering the transcriptional coactivator CREB binding protein/p300. Functionally, IFN-γ stimulation dampened bidirectional transport of IgG across a polarized Calu-3 lung epithelial monolayer. Taken together, our results indicate that the JAK/STAT-1 signaling pathway was necessary and sufficient to mediate the down-regulation of FcRn gene expression by IFN-γ. PMID:18566411

  5. Colostrogenesis: IgG1 transcytosis mechanisms.

    PubMed

    Baumrucker, Craig R; Bruckmaier, Rupert M

    2014-03-01

    Biological transport of intact proteins across epithelial cells has been documented for many absorptive and secretory tissues. Immunoglobulins were some of the earliest studied proteins in this category. The transcellular transport (transcytosis) of immunoglobulins in neonatal health and development has been recognized; the process is especially significant with ungulates because they do not transcytose immunoglobulins across the placenta to the neonate. Rather, they depend upon mammary secretion of colostrum and intestinal absorption of immunoglobulins in order to provide intestinal and systemic defense until the young ungulate develops its own humoral defense mechanisms. The neonatal dairy calf's ability to absorb immunoglobulins from colostrum is assisted by a ~24 h "open gut" phenomenon where large proteins pass the intestinal epithelial cells and enter the systemic system. However, a critical problem recognized for newborn dairy calves is that an optimum mass of colostrum Immunoglobulin G (IgG) needs to be absorbed within that 24 h window in order to provide maximal resistance to disease. Many calves do not achieve the optimum because of poor quality colostrum. While many studies have focused on calf absorption, the principal cause of the problem resides with the extreme variation (g to kg) in the mammary gland's capacity to transfer blood IgG1 into colostrum. Colostrum is a unique mammary secretory product that is formed during late pregnancy when mammary cells are proliferating and differentiating in preparation for lactation. In addition to the transcytosis of immunoglobulins, the mammary gland also concentrates a number of circulating hormones into colostrum. Remarkably, the mechanisms in the formation of colostrum in ungulates have been rather modestly studied. The mechanisms and causes of this variation in mammary gland transcytosis of IgG1 are examined, evaluated, and in some cases, explained. PMID:24474529

  6. Low cord blood type 14 pneumococcal IgG1 but not IgG2 antibody predicts early infant otitis media.

    PubMed

    Lockhart, N J; Daly, K A; Lindgren, B R; Meland, M; Le, C T; Giebink, G S

    2000-06-01

    Type-specific IgG1 and IgG2 antibodies to Streptococcus pneumoniae capsular polysaccharides 14 and 19F were measured in cord blood samples from 425 neonates, to determine which antibody subclass was most strongly associated with otitis media (OM) during the first 6 months of life (early OM). Early OM was significantly associated with type 14 IgG1 antibody in the lowest antibody quartile (P=.055) but not with type 19F IgG1 antibody or with either IgG2 antibody. IgG1 and IgG2 antibodies were significantly intercorrelated for type 14 (r=.52, P<.001) and type 19F (r=.38, P<.001). Multivariate analysis revealed that having type 14 IgG1 antibody in the lowest quartile, child care attendance, and sibling and maternal OM history were independent risk factors for early OM. Although type-specific pneumococcal IgG2 antibody concentrations were significantly higher than IgG1 concentrations, IgG2 antibodies apparently are not protective against OM during early infancy. PMID:10837178

  7. Neonatal sepsis

    MedlinePlus

    ... BE. Perinatal viral infections. In Martin RJ, Fanaroff AA, Walsh MC, eds. Fanaroff and Martin's Neonatal-Perinatal ... K. Postnatal bacterial infections. In Martin RJ, Fanaroff AA, Walsh MC, eds. Fanaroff and Martin's Neonatal-Perinatal ...

  8. [The development of the IgG concentration in the blood serum of newborn foals].

    PubMed

    Warko, G; Bostedt, H

    1993-12-01

    The aim of this study was to determine the course of the IgG concentration in blood serum of neonatal foals. A comparison of blood serum IgG concentration of the mares showed IgG values of 3356 +/- 671 mg/dl up to a maximum of 3579 +/- 766 mg/dl (means +/- s). In accordance with Eisenhauer (1981) and in contrast to Jeffcott (1974) no significant change of the IgG level in the blood serum of the mares could be observed during the test period. However, the IgG concentration in the colostrum of meanG = 11776 mg/dl during birth decreased considerably 96 hours later with meanG = 135 mg/dl. At birth in all samples, small amounts of IgG could be detected. The IgG level of the foals' blood increased rapidly after the ingestion of colostrum; 6 of 16 foals showed more than 800 mg/dl six hours post natum, reaching maximum levels 18 hours after birth with meanG = 1343 mg/dl. At 96 hours post natum, the IgG concentration dropped to meanG = 1170 mg/dl. The correlation of IgG concentration in colostrum and serum was significant. PMID:8122240

  9. Comparative functional characterization of canine IgG subclasses.

    PubMed

    Bergeron, Lisa M; McCandless, Erin E; Dunham, Steve; Dunkle, Bill; Zhu, Yaqi; Shelly, John; Lightle, Sandra; Gonzales, Andrea; Bainbridge, Graeme

    2014-01-15

    To date, very little is known about the functional characteristics of the four published canine IgG subclasses. It is not clear how each subclass engages the immune system via complement-dependent cytotoxicity (CDC) or antibody-dependent cell-mediated cytotoxicity (ADCC), or how long each antibody may last in serum. Such information is critical for understanding canine immunology and for the discovery of canine therapeutic monoclonal antibodies. Through both in vitro and ex vivo experiments to evaluate canine Fc's for effector function, complement binding, FcRn binding, and ADCC, we are now able to categorize canine subclasses by function. The subclasses share functional properties with the four human IgG subclasses and are reported herein with their function-based human analog. Canine Fc fusions, canine chimeras, and caninized antibodies were characterized. Canine subclasses A and D appear effector-function negative while subclasses B and C bind canine Fc gamma receptors and are positive for ADCC. All canine subclasses bind the neonatal Fc receptor except subclass C. By understanding canine IgGs in this way, we can apply what is known of human immunology toward translational and veterinary medicine. Thus, this body of work lays the foundation for evaluating canine IgG subclasses for therapeutic antibody development and builds upon the fundamental scholarship of canine immunology. PMID:24268690

  10. Soluble Monomeric IgG1 Fc*

    PubMed Central

    Ying, Tianlei; Chen, Weizao; Gong, Rui; Feng, Yang; Dimitrov, Dimiter S.

    2012-01-01

    Antibody fragments are emerging as promising biopharmaceuticals because of their relatively small size and other unique properties. However, compared with full-size antibodies, these antibody fragments lack the ability to bind the neonatal Fc receptor (FcRn) and have reduced half-lives. Fc engineered to bind antigens but preserve interactions with FcRn and Fc fused with monomeric proteins currently are being developed as candidate therapeutics with prolonged half-lives; in these and other cases, Fc is a dimer of two CH2-CH3 chains. To further reduce the size of Fc but preserve FcRn binding, we generated three human soluble monomeric IgG1 Fcs (mFcs) by using a combination of structure-based rational protein design combined with multiple screening strategies. These mFcs were highly soluble and retained binding to human FcRn comparable with that of Fc. These results provide direct experimental evidence that efficient binding to human FcRn does not require human Fc dimerization. The newly identified mFcs are promising for the development of mFc fusion proteins and for novel types of mFc-based therapeutic antibodies of small size and long half-lives. PMID:22518843

  11. Neonatal hypotonia.

    PubMed

    Sparks, Susan E

    2015-06-01

    Neonatal hypotonia is a common problem in the neonatal intensive care unit. The genetic differential diagnosis is broad, encompassing primary muscular dystrophies, chromosome abnormalities, neuropathies, and inborn errors of metabolism. Recognition of hypotonia is relatively straightforward, but determining the cause can be challenging. It is important for the neonatologist to have an organized approach to the assessment of neonatal hypotonia. Physical examination and history alongside basic laboratory testing and imaging aid in the differential diagnosis. Identification of the cause is essential for determining prognosis, associated morbidities, and recurrence risk. The prevailing therapeutic modality is physical, occupational, speech/feeding, and respiratory therapy. PMID:26042909

  12. Neonatal conjunctivitis

    MedlinePlus

    Newborn conjunctivitis; Conjunctivitis of the newborn; Ophthalmia neonatorum; Eye infection - neonatal conjunctivitis ... diseases spread through sexual contact to prevent newborn conjunctivitis caused by these infections. Putting eye drops into ...

  13. Neonatal Death

    MedlinePlus

    ... story First Candle Centering Corporation The Compassionate Friends Star Legacy Foundation Last reviewed: November, 2015 Neonatal death ... story First Candle Centering Corporation The Compassionate Friends Star Legacy Foundation Last reviewed: November, 2015 Complications & Loss ...

  14. Neonatal sepsis

    MedlinePlus

    ... and some strains of streptococcus. Group B streptococcus (GBS) has been a major cause of neonatal sepsis. ... an infant's risk of early-onset bacterial sepsis: GBS colonization during pregnancy Preterm delivery Water breaking (rupture ...

  15. Neonatal pain

    PubMed Central

    Walker, Suellen M

    2014-01-01

    Effective management of procedural and postoperative pain in neonates is required to minimize acute physiological and behavioral distress and may also improve acute and long-term outcomes. Painful stimuli activate nociceptive pathways, from the periphery to the cortex, in neonates and behavioral responses form the basis for validated pain assessment tools. However, there is an increasing awareness of the need to not only reduce acute behavioral responses to pain in neonates, but also to protect the developing nervous system from persistent sensitization of pain pathways and potential damaging effects of altered neural activity on central nervous system development. Analgesic requirements are influenced by age-related changes in both pharmacokinetic and pharmacodynamic response, and increasing data are available to guide safe and effective dosing with opioids and paracetamol. Regional analgesic techniques provide effective perioperative analgesia, but higher complication rates in neonates emphasize the importance of monitoring and choice of the most appropriate drug and dose. There have been significant improvements in the understanding and management of neonatal pain, but additional research evidence will further reduce the need to extrapolate data from older age groups. Translation into improved clinical care will continue to depend on an integrated approach to implementation that encompasses assessment and titration against individual response, education and training, and audit and feedback. PMID:24330444

  16. IgG Subclasses and Allotypes: From Structure to Effector Functions

    PubMed Central

    Vidarsson, Gestur; Dekkers, Gillian; Rispens, Theo

    2014-01-01

    Of the five immunoglobulin isotypes, immunoglobulin G (IgG) is most abundant in human serum. The four subclasses, IgG1, IgG2, IgG3, and IgG4, which are highly conserved, differ in their constant region, particularly in their hinges and upper CH2 domains. These regions are involved in binding to both IgG-Fc receptors (FcγR) and C1q. As a result, the different subclasses have different effector functions, both in terms of triggering FcγR-expressing cells, resulting in phagocytosis or antibody-dependent cell-mediated cytotoxicity, and activating complement. The Fc-regions also contain a binding epitope for the neonatal Fc receptor (FcRn), responsible for the extended half-life, placental transport, and bidirectional transport of IgG to mucosal surfaces. However, FcRn is also expressed in myeloid cells, where it participates in both phagocytosis and antigen presentation together with classical FcγR and complement. How these properties, IgG-polymorphisms and post-translational modification of the antibodies in the form of glycosylation, affect IgG-function will be the focus of the current review. PMID:25368619

  17. Neonatal transfusion.

    PubMed

    Kelly, Anne M; Williamson, Lorna M

    2013-11-01

    Neonates and particularly preterm neonates are frequent recipients of large volumes of blood products relative to their size. Good quality evidence for transfusion practice in this patient group has been lacking but is now increasing. Triggers for red cell transfusion are now better defined, with on-going trials of platelet transfusions likely to yield similar evidence. Transfusion is now extremely safe, but complications such as transfusion associated acute lung injury (TRALI) and transfusion associated circulatory overload (TACO) are likely to be under recognised, particularly in the sick extremely preterm neonate with respiratory symptoms. This review summarises the rationale and current practice with regard to blood component therapy. Background data on component specifications and hazards of transfusion are provided. Indications for transfusion of specific products including red cells, platelets, and plasma are discussed, and their use is illustrated by case examples. PMID:24095206

  18. Neonatal Stridor

    PubMed Central

    Daniel, Matija; Cheng, Alan

    2012-01-01

    Neonatal stridor is an important condition, in many cases implying an impending disaster with a very compromised airway. It is a sign that has to be considered with the rest of the history and examination findings, and appropriate investigations should then be undertaken to confirm the source of the noise. Neonates with stridor should be managed in a multidisciplinary setting, by clinicians familiar with the intricate physiology of these children, and with access to the multitude of medical and surgical investigative and therapeutic options required to provide first-rate care. PMID:22235209

  19. Idiopathic membranous nephropathy and IgG4: an interesting relationship

    PubMed Central

    Filippone, Edward J.

    2014-01-01

    Idiopathic membranous nephropathy (iMN) is a single-organ autoimmune disease characterized by subepithelial deposition of immune complexes containing IgG4 resulting in proteinuria, nephrotic syndrome, and, in some, end-stage renal disease. The pathogenesis involves a chronic IgG4 response against specific podocyte antigens which have now been at least partially defined in the neonatal, early childhood, and adult varieties. More has recently been learned about the genetic predisposition as well. This review discusses the pathophysiology of iMN in light of these discoveries and what is known about the genesis and potential clinical ramifications of an antigen-specific IgG4 response. PMID:23380389

  20. Neonatal meningitis.

    PubMed

    Heath, P T; Nik Yusoff, N K; Baker, C J

    2003-05-01

    Twelve years ago an annotation was published in Archives of Disease in Childhood regarding the antibiotic treatment of suspected neonatal meningitis. The authors recommended the use of cephalosporins rather than chloramphenicol and advocated intraventricular aminoglycoside treatment in selected cases. They noted the absence of clinical trials with third generation cephalosporins that showed an improvement in mortality or neurological outcome. PMID:12719388

  1. Role of immunoglobulins in neonatal sepsis

    PubMed Central

    Capasso, L; Borrelli, AC; Cerullo, J; Pisanti, R; Figliuolo, C; Izzo, F; Paccone, M; Ferrara, T; Lama, S; Raimondi, F

    2015-01-01

    Neonates, especially VLBW, are at high risk for sepsis related morbidity and mortality for immaturity of their immune system and invasive NICU practices. The paucity of immunoglobulins in preterm neonates consequently to the immaturity of immune system contributes to their high risk for systemic infection. The use of intravenous IgM enriched immunoglobulins, with higher antimicrobial activity than standard IgG, has been demonstrated in a retrospective study to reduce short term mortality in VLBW infant with proven sepsis. Larger, randomized prospective trials given the enormous burden of morbidity and mortality imposed by neonatal sepsis should urgently be addressed not only to validate this results but also to tailor the optimal scheme of treatment. PMID:25674546

  2. Neonatal Infectious Diseases: Evaluation of Neonatal Sepsis

    PubMed Central

    Spearman, Paul W.; Stoll, Barbara J.

    2015-01-01

    Synopsis Neonatal sepsis remains a feared cause of morbidity and mortality in the neonatal period. Maternal, neonatal and environmental factors are associated with risk of infection, and a combination of prevention strategies, judicious neonatal evaluation and early initiation of therapy are required to prevent adverse outcomes. The following chapter reviews recent trends in epidemiology, and provides an update on risk factors, diagnostic methods and management of neonatal sepsis. PMID:23481106

  3. [Fetal-neonatal alloimmune thrombocytopenia].

    PubMed

    Muñiz-Díaz, E; Ginovart Galiana, G

    2003-06-01

    Fetal-neonatal alloimmune thrombocytopenia is the commonest cause of severe thrombocytopenia in the newborn. This disorder is due to the destruction of fetal platelets by a maternal platelet-specific antibody caused by fetal-maternal incompatibility. The most serious complication is intracranial hemorrhage (10-30 % of newborns), which may cause death (10 % of the reported cases) or irreversible neurological sequelae (20 %). The diagnosis is usually made after birth when most affected neonates have petechiae, purpura or overt bleeding. The degree of severity varies according to platelet count. Current methods allow detection of maternal platelet alloantibodies (usually HPA-1a). Clinical grounds and the exclusion of other causes of neonatal thrombocytopenia are required to establish an accurate diagnosis. Recurrence of this disease is very high and has prompted clinicians to develop antenatal prophylactic programs in subsequent pregnancies. However, the optimal treatment of at-risk pregnancies remains controversial. The early diagnosis of this process allows effective therapy based on the infusion of compatible platelets and IgG immunoglobulins when hemorrhage is not obvious. Antenatal management of subsequent pregnancies can prevent recurrence of thrombocytopenia and intracranial hemorrhage. The aim of this review is to draw pediatricians' attention to the importance of this probably under-diagnosed disease in which early diagnosis can prevent potentially severe complications. PMID:12781112

  4. IgG4-related skin disease.

    PubMed

    Tokura, Y; Yagi, H; Yanaguchi, H; Majima, Y; Kasuya, A; Ito, T; Maekawa, M; Hashizume, H

    2014-11-01

    IgG4-related disease (IgG4-RD) is a recently established clinical entity characterized by high levels of circulating IgG4, and tissue infiltration of IgG4(+) plasma cells. IgG4-RD exhibits a distinctive fibroinflammatory change involving multiple organs, such as the pancreas and salivary and lacrimal glands. The skin lesions of IgG4-RD have been poorly characterized and may stem not only from direct infiltration of plasma cells but also from IgG4-mediated inflammation. Based on the documented cases together with ours, we categorized the skin lesions into seven subtypes: (1) cutaneous plasmacytosis (multiple papulonodules or indurations on the trunk and proximal part of the limbs), (2) pseudolymphoma and angiolymphoid hyperplasia with eosinophilia (plaques and papulonodules mainly on the periauricular, cheek and mandible regions), (3) Mikulicz disease (palpebral swelling, sicca syndrome and exophthalmos), (4) psoriasis-like eruption (strikingly mimicking psoriasis vulgaris), (5) unspecified maculopapular or erythematous eruptions, (6) hypergammaglobulinaemic purpura (bilateral asymmetrical palpable purpuric lesions on the lower extremities) and urticarial vasculitis (prolonged urticarial lesions occasionally with purpura) and (7) ischaemic digit (Raynaud phenomenon and digital gangrene). It is considered that subtypes 1-3 are induced by direct infiltration of IgG4(+) plasma cells, while the other types (4-7) are caused by secondary mechanisms. IgG4-related skin disease is defined as IgG4(+) plasma-cell-infiltrating skin lesions that form plaques, nodules or tumours (types 1-3), but may manifest secondary lesions caused by IgG4(+) plasma cells and/or IgG4 (types 4-7). PMID:25065694

  5. Divergent outcomes following transcytosis of IgG targeting intracellular and extracellular chlamydial antigens

    PubMed Central

    Armitage, Charles W; O’Meara, Connor P; Harvie, Marina CG; Timms, Peter; Blumberg, Richard S; Beagley, Kenneth W

    2014-01-01

    Antibodies can have a protective but non-essential role in natural chlamydial infections dependent on antigen specificity and antibody isotype. IgG is the dominant antibody in both male and female reproductive tract mucosal secretions, and is bi-directionally trafficked across epithelia by the neonatal Fc receptor (FcRn). Using pH-polarized epididymal epithelia grown on Transwells, IgG specifically targeted at an extracellular chlamydial antigen; the major outer membrane protein (MOMP), enhanced uptake and translocation of infection at pH 6–6.5 but not at neutral pH. This was dependent on FcRn expression. Conversely, FcRn-mediated transport of IgG targeting the intracellular chlamydial inclusion membrane protein A (IncA), induced aberrant inclusion morphology, recruited autophagic proteins independent of lysosomes and significantly reduced infection. Challenge of female mice with MOMP-specific IgG-opsonized Chlamydia muridarum delayed infection clearance but exacerbated oviduct occlusion. In male mice, MOMP-IgG elicited by immunization afforded no protection against testicular chlamydial infection, whereas the transcytosis of IncA-IgG significantly reduced testicular chlamydial burden. Together these data show that the protective and pathological effects of IgG are dependent on FcRn-mediated transport as well as the specificity of IgG for intracellular or extracellular antigens. PMID:24445600

  6. Pros and cons of VP1-specific maternal IgG for the protection of Enterovirus 71 infection.

    PubMed

    Kim, Young-In; Song, Jae-Hyoung; Kwon, Bo-Eun; Kim, Ha-Neul; Seo, Min-Duk; Park, KwiSung; Lee, SangWon; Yeo, Sang-Gu; Kweon, Mi-Na; Ko, Hyun-Jeong; Chang, Sun-Young

    2015-11-27

    Enterovirus 71 (EV71) causes hand, foot, and mouth diseases and can result in severe neurological disorders when it infects the central nervous system. Thus, there is a need for the development of effective vaccines against EV71 infection. Here we report that viral capsid protein 1 (VP1), one of the main capsid proteins of EV71, efficiently elicited VP1-specific immunoglobulin G (IgG) in the serum of mice immunized with recombinant VP1. The VP1-specific IgG produced in female mice was efficiently transferred to their offspring, conferring protection against EV71 infection immediately after birth. VP1-specific antibody can neutralize EV71 infection and protect host cells. VP1-specific maternal IgG in offspring was maintained for over 6 months. However, the pre-existence of VP1-specific maternal IgG interfered with the production of VP1-specific IgG antibody secreting cells by active immunization in offspring. Therefore, although our results showed the potential for VP1-specific maternal IgG protection against EV71 in neonatal mice, other strategies must be developed to overcome the hindrance of maternal IgG in active immunization. In this study, we developed an effective and feasible animal model to evaluate the protective efficacy of humoral immunity against EV71 infection using a maternal immunity concept. PMID:26529069

  7. Neonatal circumcision.

    PubMed

    Lerman, S E; Liao, J C

    2001-12-01

    The merits of neonatal circumcision continue to be debated hotly. Some argue that circumcision is a "uniquely American medical enigma." Most of the world's male population remains uncircumcised; however, most boys born in the United States continue to undergo neonatal circumcision. Review of existing literature supports that most children who are uncircumcised do well from a medical standpoint and, thus, the question of whether US health care practitioners are subjecting neonates to an unnecessary surgical procedure remains. The medical benefits of circumcision are multiple, but most are small. The clearest medical benefit of circumcision is the relative reduction in the risk for a UTI, especially in early infancy. Although this risk [figure: see text] is real, the absolute numbers are small (risk ranges from 1 in 100 to 1 in 1000), and one investigator has estimated that it may take approximately 80 neonatal circumcisions to prevent one UTI. In the case of a patient with known urologic abnormalities that predispose to UTI, neonatal circumcision has a clearer role in terms of medical benefit to the patient. Most of the other medical benefits of circumcision probably can be realized without circumcision as long as access to clean water and proper penile hygiene are achieved. Proper penile hygiene should all but eliminate the risk for foreskin-related medical problems that will require circumcision. Moreover, proper hygiene and access to clean water has been shown to reduce the rate of development of squamous cell carcinoma of the penis in the uncircumcised population. Proper techniques on the care of the foreskin are illustrated in the American Academy of Pediatrics pamphlet titled "How to care for the uncircumcised penis." Regarding the relationship between STDs and circumcision, patient education and the practice of low-risk sexual behavior make a far greater impact than does routine circumcision in hopes of reducing the spread of HIV and other STDs. Nevertheless

  8. Neonatal Fc receptor promotes immune complex-mediated glomerular disease.

    PubMed

    Olaru, Florina; Luo, Wentian; Suleiman, Hani; St John, Patricia L; Ge, Linna; Mezo, Adam R; Shaw, Andrey S; Abrahamson, Dale R; Miner, Jeffrey H; Borza, Dorin-Bogdan

    2014-05-01

    The neonatal Fc receptor (FcRn) is a major regulator of IgG and albumin homeostasis systemically and in the kidneys. We investigated the role of FcRn in the development of immune complex-mediated glomerular disease in mice. C57Bl/6 mice immunized with the noncollagenous domain of the α3 chain of type IV collagen (α3NC1) developed albuminuria associated with granular capillary loop deposition of exogenous antigen, mouse IgG, C3 and C5b-9, and podocyte injury. High-resolution imaging showed abundant IgG deposition in the expanded glomerular basement membrane, especially in regions corresponding to subepithelial electron dense deposits. FcRn-null and -humanized mice immunized with α3NC1 developed no albuminuria and had lower levels of serum IgG anti-α3NC1 antibodies and reduced glomerular deposition of IgG, antigen, and complement. Our results show that FcRn promotes the formation of subepithelial immune complexes and subsequent glomerular pathology leading to proteinuria, potentially by maintaining higher serum levels of pathogenic IgG antibodies. Therefore, reducing pathogenic IgG levels by pharmacologic inhibition of FcRn may provide a novel approach for the treatment of immune complex-mediated glomerular diseases. As proof of concept, we showed that a peptide inhibiting the interaction between human FcRn and human IgG accelerated the degradation of human IgG anti-α3NC1 autoantibodies injected into FCRN-humanized mice as effectively as genetic ablation of FcRn, thus preventing the glomerular deposition of immune complexes containing human IgG. PMID:24357670

  9. Neonatal Fc Receptor Promotes Immune Complex–Mediated Glomerular Disease

    PubMed Central

    Olaru, Florina; Luo, Wentian; Suleiman, Hani; St. John, Patricia L.; Ge, Linna; Mezo, Adam R.; Shaw, Andrey S.; Abrahamson, Dale R.; Miner, Jeffrey H.

    2014-01-01

    The neonatal Fc receptor (FcRn) is a major regulator of IgG and albumin homeostasis systemically and in the kidneys. We investigated the role of FcRn in the development of immune complex–mediated glomerular disease in mice. C57Bl/6 mice immunized with the noncollagenous domain of the α3 chain of type IV collagen (α3NC1) developed albuminuria associated with granular capillary loop deposition of exogenous antigen, mouse IgG, C3 and C5b-9, and podocyte injury. High-resolution imaging showed abundant IgG deposition in the expanded glomerular basement membrane, especially in regions corresponding to subepithelial electron dense deposits. FcRn-null and -humanized mice immunized with α3NC1 developed no albuminuria and had lower levels of serum IgG anti-α3NC1 antibodies and reduced glomerular deposition of IgG, antigen, and complement. Our results show that FcRn promotes the formation of subepithelial immune complexes and subsequent glomerular pathology leading to proteinuria, potentially by maintaining higher serum levels of pathogenic IgG antibodies. Therefore, reducing pathogenic IgG levels by pharmacologic inhibition of FcRn may provide a novel approach for the treatment of immune complex–mediated glomerular diseases. As proof of concept, we showed that a peptide inhibiting the interaction between human FcRn and human IgG accelerated the degradation of human IgG anti-α3NC1 autoantibodies injected into FCRN-humanized mice as effectively as genetic ablation of FcRn, thus preventing the glomerular deposition of immune complexes containing human IgG. PMID:24357670

  10. IgG4-related spinal pachymeningitis.

    PubMed

    Lu, Zhang; Tongxi, Liu; Jie, Luo; Yujuan, Jiao; Wei, Jiang; Xia, Liu; Yumin, Zheng; Xin, Lu

    2016-06-01

    The aim of this study is to study the clinical, laboratory, imaging pathology, and prognosis features of IgG4-related spinal pachymeningitis. We worked with a 55-year-old man suffering from IgG4-related spinal pachymeningitis who had the most widespread lesion in his dura mater. We also review previous related studies and discuss the clinical characteristics of this rare disease. In total, eight IgG4-related spinal pachymeningitis patients have been reported in the literature since 2009. They were mostly male patients, 51.7 ± 11.9 years old on average. Cervical and thoracic vertebrae were the most common sites for lesions. The most prominent symptom was varying numbness and weakness of the limbs and/or body associated with spinal cord compression. There was one patient (1/5) with elevated serum IgG4 levels and three patients (3/3) with increased cerebrospinal fluid (CSF) IgG4 index. Positive histopathologic findings are the strongest basis for a diagnosis. All the patients with IgG4-related spinal pachymeningitis responded well to glucocorticoid therapy. IgG4-related spinal pachymeningitis is an orphan disease that mainly occurs in cervical and thoracic vertebrae. Older males are the most susceptible group. Serum IgG4 levels were consistently normal in these cases, so analysis of CSF for IgG4 production (IgG4 index) could become a useful tool. Pathological findings remain the gold standard for diagnosis. Most patients responded favorably to glucocorticoid treatment. PMID:26567899

  11. Measurement of serum IgG in foals by radial immunodiffusion and automated turbidimetric immunoassay.

    PubMed

    Davis, Deborah G; Schaefer, Deanna M W; Hinchcliff, Kenneth W; Wellman, Maxey L; Willet, V Ellen; Fletcher, Jana M

    2005-01-01

    Hypogammaglobulinemia as a result of failure of transfer of passive immunity (FTPI) is an important risk factor for infectious disease in neonatal foals. The current gold standard for determining serum immunoglobulin concentrations is radial immunodiffusion (RID). The purpose of this study was to compare immunoglobulin concentrations measured by RID with those determined by an automated turbidimetric immunoassay (TIA), which has a much shorter turnaround time. Immunoglobulin concentrations were measured by both RID and TIA in serum collected from 84 neonatal foals. Sixty-seven foals had results within the linear range for both assays. Sensitivity and specificity of TIA for diagnosis of FTPI with IgG < or = 800 mg/dL were 0.81 (95% CI 0.70-0.88) and 0.86 (95% CI 0.76-0.93) and with IgG < or = 400 mg/dL were 0.63 (95% CI 0.35-0.86) and 0.92 (95% CI 0.87-0.95), respectively. A significant linear relationship was found between IgG concentrations determined by TIA and RID (TIA = 0.9511RID + 8.4354; R2 = .59, P < .0001). The coefficients of variation for between-run and within-run precision for the TIA were 2.5 and 3%, respectively. Storage of samples from 10 foals at -20 degrees C for 10-12 months resulted in a reduction in TIA-measured serum IgG concentration of -17.6% (SD = 3.7%), indicating that long-term storage of samples at -20 degrees C should be avoided. The results of this study indicate that measurement of serum IgG by TIA can be used to evaluate foals for FTPI. PMID:15715054

  12. The future of neonatal BCG.

    PubMed

    Odent, Michel R

    2016-06-01

    We hypothesise that neonatal BCG (Bacillus Calmette-Guérin) might be used to adapt to a new phase in the history of human births. Among most mammals, the placenta is not effective at transferring antibodies to the fetus: antibodies are transferred immediately after birth via the colostrum. Among humans (and other mammals with hemochorial placentas) the transplacental transfer of antibodies (namely IgG) is effective. In humans, foetal concentrations of IgG sub-classes approximate to maternal concentrations at 38weeks and continue to increase thereafter. These facts explain inter-species differences regarding the basic needs of neonates. Among most mammals, the early colostrum is, strictly speaking, vital. Among humans, the main questions are about the bacteriological environment in the birthing place and how familiar it is to the mother. Today, most human beings are born in unfamiliar bacteriological environments characterized by a low microbial diversity. The effects of clinical environments may be amplified by the use of antibiotics and birth by caesarean, i.e. by-passing the bacteriologically rich perineal zone. There is already an accumulation of data confirming that the maturation of a balanced Th1/Th2 immune response is affected by the mode of delivery. There is also an accumulation of epidemiological studies detecting risk factors in the perinatal period for health conditions such as type 1 diabetes (and other autoimmune diseases), atopy, autism and obesity. In such a context there are reasons to plan randomized controlled trials with long term follow-up of the effects of BCG given immediately after birth, as a modulator of Th-1/Th-2 responses. A follow-up period in the region of 6-10years would be long enough to evaluate the prevalence of several nosologically well defined diseases. These studies would be ethically acceptable, since BCG is the only infancy vaccine that has been evaluated through randomised controlled trials with long term follow

  13. Adverse effects of IgG therapy.

    PubMed

    Berger, Melvin

    2013-01-01

    IgG is widely used for patients with immune deficiencies and in a broad range of autoimmune and inflammatory disorders. Up to 40% of intravenous infusions of IgG may be associated with adverse effects (AEs), which are mostly uncomfortable or unpleasant but often are not serious. The most common infusion-related AE is headache. More serious reactions, including true anaphylaxis and anaphylactoid reactions, occur less frequently. Most reactions are related to the rate of infusion and can be prevented or treated just by slowing the infusion rate. Medications such as nonsteroidal anti-inflammatory drugs, antihistamines, or corticosteroids also may be helpful in preventing or treating these common AEs. IgA deficiency with the potential of IgG or IgE antibodies against IgA increases the risk of some AEs but should not be viewed as a contraindication if IgG therapy is needed. Potentially serious AEs include renal dysfunction and/or failure, thromboembolic events, and acute hemolysis. These events usually are multifactorial, related to combinations of constituents in the IgG product as well as risk factors for the recipient. Awareness of these factors should allow minimization of the risks and consequences of these AEs. Subcutaneous IgG is absorbed more slowly into the circulation and has a lower incidence of AEs, but awareness and diligence are necessary whenever IgG is administered. PMID:24565701

  14. [A neonate with pustules].

    PubMed

    Groot, Dominique T; van den Broek, Annique J M

    2016-01-01

    We describe a female neonate with non-grouped pustules directly postpartum without clinical signs of illness. There were no red maculae. At follow-up some pustules had turned to pigmented maculae, which confirmed the diagnosis of neonatal pustular melanosis. This benign transient condition occurs in 4-8% of dark-coloured neonates and in <1% of white neonates. PMID:26840934

  15. Neonatal resuscitation: Current issues

    PubMed Central

    Chadha, Indu A

    2010-01-01

    The following guidelines are intended for practitioners responsible for resuscitating neonates. They apply primarily to neonates undergoing transition from intrauterine to extrauterine life. The updated guidelines on Neonatal Resuscitation have assimilated the latest evidence in neonatal resuscitation. Important changes with regard to the old guidelines and recommendations for daily practice are provided. Current controversial issues concerning neonatal resuscitation are reviewed and argued in the context of the ILCOR 2005 consensus. PMID:21189881

  16. [Neonatal cholestasis].

    PubMed

    Lacaille, F

    2016-03-01

    "Cholestasis" means abnormal synthesis or secretion of bile. The main symptom in a neonate or infant is jaundice. Urine is dark, staining diapers, and stools are variably pale or white. Vitamin K should be injected (to prevent coagulation disorders due to malabsorption). The two diagnoses requiring urgent treatment are urinary tract infection and biliary atresia. If stools are permanently white, biliary atresia is highly probable. A few genetic causes of intrahepatic cholestasis should be screened and corrective surgery organized. The diseases responsible for cholestasis in this age group are described as well as the investigations and treatments, including the management of non-specific complications of cholestasis. A delay in the diagnosis of biliary atresia can have such severe consequences that consultation with a hepatology unit or transfer should be easy and rapid. PMID:26850153

  17. Pathologies Associated with Serum IgG4 Elevation

    PubMed Central

    Ebbo, Mikael; Grados, Aurélie; Bernit, Emmanuelle; Vély, Frederic; Boucraut, José; Harlé, Jean-Robert; Daniel, Laurent; Schleinitz, Nicolas

    2012-01-01

    Statement of Purpose. IgG4-related disease (IgG4-RD) is usually associated to an increase of serum IgG4 levels. However other conditions have also been associated to high serum IgG4 levels. Methods. All IgG subclasses analyses performed in our hospital over a one-year period were analyzed. When IgG4 level were over 1.35 g/L, the patient's clinical observation was analyzed and both final diagnosis and reason leading to IgG subclasses analysis were recorded. Only polyclonal increases of IgG4 were considered. Summary of the Results. On 646 IgG subclass analysis performed, 59 patients had serum IgG4 over 1.35 g/L. The final diagnosis associated to serum IgG4 increase was very variable. Most patients (25%) presented with repeated infections, 13.5% with autoimmune diseases, and 10% with IgG4-RD. Other patients presented with cancer, primary immune deficiencies, idiopathic interstitial lung disease, cystic fibrosis, histiocytosis, or systemic vasculitis and 13.5% presented with various pathologies or no diagnosis. Mean IgG4 levels and IgG4/IgG ratio were higher in IgG4-RD than in other pathologies associated to elevated IgG4 levels. Conclusions. Our study confirms that elevation of serum IgG4 is not specific to IgG4-RD. Before retaining IgG4-RD diagnosis in cases of serum IgG4 above 1.35 g/L, several other pathological conditions should be excluded. PMID:22966232

  18. A prominent lack of IgG1-Fc fucosylation of platelet alloantibodies in pregnancy

    PubMed Central

    Kapur, Rick; Kustiawan, Iwan; Vestrheim, Anne; Koeleman, Carolien A. M.; Visser, Remco; Einarsdottir, Helga K.; Porcelijn, Leendert; Jackson, Dave; Kumpel, Belinda; Deelder, André M.; Blank, Dennis; Skogen, Björn; Killie, Mette Kjaer; Michaelsen, Terje E.; de Haas, Masja; Rispens, Theo; van der Schoot, C. Ellen; Wuhrer, Manfred

    2014-01-01

    Immunoglobulin G (IgG) formed during pregnancy against human platelet antigens (HPAs) of the fetus mediates fetal or neonatal alloimmune thrombocytopenia (FNAIT). Because antibody titer or isotype does not strictly correlate with disease severity, we investigated by mass spectrometry variations in the glycosylation at Asn297 in the IgG Fc because the composition of this glycan can be highly variable, affecting binding to phagocyte IgG-Fc receptors (FcγR). We found markedly decreased levels of core fucosylation of anti-HPA-1a–specific IgG1 from FNAIT patients (n = 48), but not in total serum IgG1. Antibodies with a low amount of fucose displayed higher binding affinity to FcγRIIIa and FcγRIIIb, but not to FcγRIIa, compared with antibodies with a high amount of Fc fucose. Consequently, these antibodies with a low amount of Fc fucose showed enhanced phagocytosis of platelets using FcγRIIIb+ polymorphonuclear cells or FcγRIIIa+ monocytes as effector cells, but not with FcγRIIIa– monocytes. In addition, the degree of anti-HPA-1a fucosylation correlated positively with the neonatal platelet counts in FNAIT, and negatively to the clinical disease severity. In contrast to the FNAIT patients, no changes in core fucosylation were observed for anti-HLA antibodies in refractory thrombocytopenia (post platelet transfusion), indicating that the level of fucosylation may be antigen dependent and/or related to the immune milieu defined by pregnancy. PMID:24243971

  19. A prominent lack of IgG1-Fc fucosylation of platelet alloantibodies in pregnancy.

    PubMed

    Kapur, Rick; Kustiawan, Iwan; Vestrheim, Anne; Koeleman, Carolien A M; Visser, Remco; Einarsdottir, Helga K; Porcelijn, Leendert; Jackson, Dave; Kumpel, Belinda; Deelder, André M; Blank, Dennis; Skogen, Björn; Killie, Mette Kjaer; Michaelsen, Terje E; de Haas, Masja; Rispens, Theo; van der Schoot, C Ellen; Wuhrer, Manfred; Vidarsson, Gestur

    2014-01-23

    Immunoglobulin G (IgG) formed during pregnancy against human platelet antigens (HPAs) of the fetus mediates fetal or neonatal alloimmune thrombocytopenia (FNAIT). Because antibody titer or isotype does not strictly correlate with disease severity, we investigated by mass spectrometry variations in the glycosylation at Asn297 in the IgG Fc because the composition of this glycan can be highly variable, affecting binding to phagocyte IgG-Fc receptors (FcγR). We found markedly decreased levels of core fucosylation of anti-HPA-1a-specific IgG1 from FNAIT patients (n = 48), but not in total serum IgG1. Antibodies with a low amount of fucose displayed higher binding affinity to FcγRIIIa and FcγRIIIb, but not to FcγRIIa, compared with antibodies with a high amount of Fc fucose. Consequently, these antibodies with a low amount of Fc fucose showed enhanced phagocytosis of platelets using FcγRIIIb(+) polymorphonuclear cells or FcγRIIIa(+) monocytes as effector cells, but not with FcγRIIIa(-) monocytes. In addition, the degree of anti-HPA-1a fucosylation correlated positively with the neonatal platelet counts in FNAIT, and negatively to the clinical disease severity. In contrast to the FNAIT patients, no changes in core fucosylation were observed for anti-HLA antibodies in refractory thrombocytopenia (post platelet transfusion), indicating that the level of fucosylation may be antigen dependent and/or related to the immune milieu defined by pregnancy. PMID:24243971

  20. IgG expression in trophoblasts derived from placenta and gestational trophoblastic disease and its role in regulating invasion.

    PubMed

    Yang, Mei; Ha, Chunfang; Liu, Dan; Xu, Yonghui; Ma, Yuan; Liu, Yufeng; Nian, Yan

    2014-10-01

    Immunoglobulin G (IgG) is an important humoral immune factor, which plays a role in innate immunity of the fetus. IgG immunoreactivity was often seen in trophoblasts of placenta. Traditionally, IgG in trophoblasts was believed to be transported from the maternal blood through neonatal Fc receptor (FcRn). Here, we explored the phenomenon of IgG expression and its role in regulating invasion in trophoblasts derived from normal placenta and gestational trophoblastic disease (GTD). IgG expression was detected with an emphasis on mRNA transcripts by using reverse transcription-polymerase chain reaction and hybridization in situ, besides evaluated at the protein level with immunohistochemistry and immunofluorescence. The migration and attachment of normal trophoblast cell line (TEV-1) and choriocarcinoma cell line (JAR) were inhibited with down-regulation of IgG expression. Methotrexate promoted the differentiation of JAR cell line; however, it had little effect on the differentiation of TEV-1 cell line. IgG expression, migration, and attachment of JAR and TEV-1 cell lines were decreased in the presence of methotrexate. Furthermore, statistical analysis showed that the differences in migration and attachment were significant (P < 0.05) for JAR cell line, while no significant difference was found for TEV-1 cell line. Collectively, these results confirmed that with the progression from normal placenta to GTD, the expression of IgG was increased in trophoblasts, which might actively promote the migration and attachment of trophoblasts as an important regulating factor. PMID:24469916

  1. Neonatal lupus erythematosus associated with unilateral pectoralis major atrophy.

    PubMed

    Mondal, Rakesh; Nandi, Madhumita; Sarkar, Sumantra; Mukherjee, Krishnendu

    2011-11-01

    Neonatal lupus erythematosus (NLE), in most cases, presents with cardiac and dermatological manifestation due to transferred IgG auto antibodies (anti Ro/SSA and anti La/SSB) from the mother. Some unusual associations with myelopathy, vasculopathy, transient myasthenia gravis, congenital nephrotic syndrome, chondrodysplasia punctata etc. are also reported. Here, the authors present a case of NLE with isolated left sided pectoralis major muscle atrophy, which has not been reported earlier. PMID:21553209

  2. Neonatal euthanasia.

    PubMed

    Kon, Alexander A

    2009-12-01

    Despite advances in the care of infants, there remain many newborns whose medical conditions are incompatible with sustained life. At times, healthcare providers and parents may agree that prolonging life is not an appropriate goal of care, and they may redirect treatment to alleviate suffering. While pediatric palliative treatment protocols are gaining greater acceptance, there remain some children whose suffering is unrelenting despite maximal efforts. Due to the realization that some infants suffer unbearably (ie, the burdens of suffering outweigh the benefits of life), the Dutch have developed a protocol for euthanizing these newborns. In this review, I examine the ethical aspects of 6 forms of end of life care, explain the ethical arguments in support of euthanasia, review the history and verbiage of the United States regulations governing limiting and withdrawing life-prolonging interventions in infants, describe the 3 categories of neonates for whom the Dutch provide euthanasia, review the published analyses of the Dutch protocol, and finally present some practical considerations should some form of euthanasia ever be deemed appropriate. PMID:19914522

  3. FcRn-mediated intestinal absorption of IgG anti-IgE/IgE immune complexes in mice

    PubMed Central

    Paveglio, Sara; Puddington, Lynn; Rafti, Ektor; Matson, Adam P.

    2012-01-01

    Background The mechanism(s) responsible for the acquisition of maternal antibody isotypes other than IgG are not fully understood. Objective To define the ability of the neonatal Fc receptor for IgG uptake (FcRn) to mediate intestinal absorption of IgG1 anti-IgE/IgE immune complexes. Methods C57BL/6 allergic ovalbumin (OVA)-immune foster mothers were generated to nurse naïve FcRn+/− or FcRn−/− progeny. At the time of weaning, serum levels of OVA-specific antibodies and IgG1 anti-IgE/IgE immune complexes were determined in allergic foster mothers and FcRn+/+, FcRn+/−, or FcRn−/− breastfed offspring. In separate experiments, FcRn+/− or FcRn−/− neonatal mice were gavage fed TNP-specific IgE as IgG1 anti-IgE/IgE immune complexes, IgG1 isotype control and IgE, or IgE alone. Mice were sacrificed 2 hours after feeding to determine serum levels and biologic activity of absorbed TNP-specific IgE. Results As expected, the absorption of maternal OVA-specific IgG1 in FcRn−/− offspring was at levels 103–104 less than observed in FcRn+/+ or FcRn+/− offspring. Surprisingly, FcRn expression also influenced the absorption of maternal IgE. OVA-specific IgE was detected in FcRn+/+ and FcRn+/− offspring, but not in FcRn−/− offspring. IgG1 anti-IgE/IgE immune complexes were detected in allergic foster mothers and correlated strongly with levels in FcRn+/+ and FcRn+/− offspring (rho=0.88, P <0.0001). Furthermore, FcRn expression was required for neonatal mice to absorb TNP-specific IgE when fed as IgG1 anti-IgE/IgE immune complexes. When immune complexes were generated with IgG1 anti-IgE directed against the Cε4 domain, the absorbed IgE was able to function in antigen-dependent basophil degranulation. Conclusions and Clinical Relevance These data demonstrate a novel mechanism by which FcRn may facilitate absorption of maternal antibodies other than IgG. These findings are clinically relevant because FcRn mediates the transplacental passage of maternal

  4. IgG4-Related Kidney Disease and IgG4-Related Retroperitoneal Fibrosis.

    PubMed

    Kawano, Mitsuhiro; Yamada, Kazunori

    2016-08-01

    Immunoglobulin G4-related kidney disease (IgG4-RKD) is the collective name encompassing renal parenchymal and renal pelvic lesions. The hallmark of renal parenchymal lesions of IgG4-related disease is plasma cell-rich tubulointerstitial nephritis with numerous IgG4-positive plasma cells and characteristic fibrosis. In addition, glomerular lesions are sometimes present, with membranous glomerulonephritis being the most common. Although IgG4-RKD shows good responsiveness to corticosteroid therapy, follow-up imaging studies have revealed that partial cortical scars persist when the start of therapy is delayed. In this review, the authors provide an overview of the latest knowledge of IgG4-RKD, focusing in particular on its pathological and imaging characteristic features. PMID:27466797

  5. Routine neonatal circumcision?

    PubMed Central

    Tran, P. T.; Giacomantonio, M.

    1996-01-01

    Routine neonatal circumcision is still a controversial procedure. This article attempts to clarify some of the advantages and disadvantages of neonatal circumcision. The increased rate of penile cancer among uncircumcised men appears to justify the procedure, but that alone is not sufficient justification. The final decision on neonatal circumcision should be made by parents with balanced counsel from attending physicians. PMID:8939321

  6. Histopathology of IgG4-Related Autoimmune Hepatitis and IgG4-Related Hepatopathy in IgG4-Related Disease.

    PubMed

    Nakanuma, Yasuni; Ishizu, Yoji; Zen, Yoh; Harada, Kenichi; Umemura, Takeji

    2016-08-01

    Immunoglobulin G4-related disease (IgG4-RD) is a systemic disease involving many organs; it includes IgG4-related sclerosing cholangitis and inflammatory pseudotumor in the hepatobiliary system. Two types of hepatic parenchymal involvement have been reported in IgG4-RD: IgG4-related autoimmune hepatitis (AIH) and IgG4-hepatopathy. Moreover, only three cases of IgG4-related AIH have been reported. Immunoglobulin G4-related AIH is clinicopathologically similar to AIH, except for an elevated serum IgG4 level and heavy infiltration of IgG4-positive plasma cells in the liver tissue. Interestingly, IgG4-related AIH can be complicated by well-known IgG4-RD(s). Immunoglobulin G4-hepatopathy, which includes various histopathological lesions encountered in the liver of patients with type I autoimmune pancreatitis, is classified into five histological categories: portal inflammation, large bile duct damage, portal sclerosis, lobular hepatitis, and cholestasis. Immunoglobulin G4-hepatopathy is currently a collective term covering hepatic lesions primarily or secondarily related to IgG4-related sclerosing cholangitis and type 1 autoimmune pancreatitis. In conclusion, the liver is not immune to IgG4-RD, and at least two types of hepatic involvement in IgG4-RD have been reported: IgG4-related AIH and IgG4-hepatopathy. Additional studies are required to clarify their precise clinical significance with respect to IgG4-RD and inherent liver diseases. PMID:27466793

  7. IgG Subclass Staining in Routine Renal Biopsy Material.

    PubMed

    Hemminger, Jessica; Nadasdy, Gyongyi; Satoskar, Anjali; Brodsky, Sergey V; Nadasdy, Tibor

    2016-05-01

    Immunofluorescence staining plays a vital role in nephropathology, but the panel of antibodies used has not changed for decades. Further classification of immunoglobulin (Ig)G-containing immune-type deposits with IgG subclass staining (IgG1, IgG2, IgG3, and IgG4) has been shown to be of diagnostic utility in glomerular diseases, but their value in the evaluation of renal biopsies has not been addressed systematically in large renal biopsy material. Between January 2007 and June 2014, using direct immunofluorescence, we stained every renal biopsy for the IgG subclasses if there was moderate to prominent glomerular IgG staining and/or IgG-predominant or IgG-codominant glomerular staining. The total number of biopsies stained was 1084, which included 367 cases of membranous glomerulonephritis, 307 cases of lupus nephritis, 74 cases of fibrillary glomerulonephritis, 53 cases of proliferative glomerulonephritis with monoclonal IgG deposits, and 25 cases of antiglomerular basement membrane disease, among others. We found that monoclonality of IgG deposits cannot always be reliably determined on the basis of kappa and lambda light chain staining alone, particularly if concomitant (frequently nonspecific) IgM staining is present. In IgG heavy and heavy and light chain deposition disease (3 cases), subclass staining is very helpful, and in proliferative glomerulonephritis with monoclonal IgG deposits subclass staining is necessary. IgG subclass staining is useful in differentiating primary from secondary membranous glomerulonephritis. In proliferative glomerulonephritis with polyclonal IgG deposition, IgG1 dominance/codominance with concomitant IgG3 and IgG2 but weak or absent IgG4 staining favors an underlying autoimmune disease. IgG subclass staining is a very useful diagnostic method in a selected cohort of renal biopsies, particularly in biopsies with glomerulonephritis with monoclonal IgG deposits. PMID:26848798

  8. Immune Responses in Neonates

    PubMed Central

    Basha, Saleem; Surendran, Naveen; Pichichero, Michael

    2015-01-01

    Neonates have little immunological memory and a developing immune system, which increases their vulnerability to infectious agents. Recent advances in understanding of neonatal immunity indicate that both innate and adaptive responses are dependent on precursor frequency of lymphocytes, antigenic dose and mode of exposure. Studies in neonatal mouse models and human umbilical cord blood cells demonstrate the capability of neonatal immune cells to produce immune responses similar to adults in some aspects but not others. This review focuses mainly on the developmental and functional mechanisms of the human neonatal immune system. In particular, the mechanism of innate and adaptive immunity and the role of neutrophils, antigen presenting cells, differences in subclasses of T lymphocytes (Th1, Th2, Tregs) and B cells are discussed. In addition, we have included the recent developments in neonatal mouse immune system. Understanding neonatal immunity is essential to development of therapeutic vaccines to combat newly emerging infectious agents. PMID:25088080

  9. Neonatal Fc Receptor Mediates Internalization of Fc in Transfected Human Endothelial Cells

    PubMed Central

    Goebl, Nancy A.; Babbey, Clifford M.; Datta-Mannan, Amita; Witcher, Derrick R.; Wroblewski, Victor J.

    2008-01-01

    The neonatal Fc receptor, FcRn mediates an endocytic salvage pathway that prevents degradation of IgG, thus contributing to the homeostasis of circulating IgG. Based on the low affinity of IgG for FcRn at neutral pH, internalization of IgG by endothelial cells is generally believed to occur via fluid-phase endocytosis. To investigate the role of FcRn in IgG internalization, we used quantitative confocal microscopy to characterize internalization of fluorescent Fc molecules by HULEC-5A lung microvascular endothelia transfected with GFP fusion proteins of human or mouse FcRn. In these studies, cells transfected with FcRn accumulated significantly more intracellular Fc than untransfected cells. Internalization of FcRn-binding forms of Fc was proportional to FcRn expression level, was enriched relative to dextran internalization in proportion to FcRn expression level, and was blocked by incubation with excess unlabeled Fc. Because we were unable to detect either surface expression of FcRn or surface binding of Fc, these results suggest that FcRn-dependent internalization of Fc may occur through sequestration of Fc by FcRn in early endosomes. These studies indicate that FcRn-dependent internalization of IgG may be important not only in cells taking up IgG from an extracellular acidic space, but also in endothelial cells participating in homeostatic regulation of circulating IgG levels. PMID:18843053

  10. Assessment of naturally occurring covalent and total dimer levels in human IgG1 and IgG2.

    PubMed

    Yang, Jane; Goetze, Andrew M; Flynn, Gregory C

    2014-03-01

    Antibody dimers, two self-associated monomers, have been detected on both recombinantly expressed and endogenous human IgG proteins. Nearly 10 years ago, Yoo et al. (2003) described low levels of IgG2 covalent dimer, in human serum, but did not quantify the levels. Here we quantify the total and covalent dimer levels of IgG2 and IgG1 in human blood, and study the origin of covalent dimer formation. Low levels (<1%) of total IgG1 and IgG2 dimers were measured in freshly prepared human plasma. Both IgG1 and IgG2 covalent dimers were also found in plasma. Whereas IgG1 covalent dimer levels were significantly reduced by steps intended to eliminate artifacts during sample preparation, IgG2 covalent dimer levels remain stable in such conditions. About 0.4% of IgG2 in plasma was in a covalent dimer form, yet very little (<0.03%) of IgG1 covalent dimer could be considered naturally occurring. IgG2 dimer also formed in vitro under conditions designed to mimic those in blood, suggesting that formation occurs in vivo during circulation. Thus, small amounts of covalent IgG2 dimer do appear to form naturally. PMID:24321397

  11. Efficient Mucosal Delivery of Vaccine Using the FcRn-Mediated IgG Transfer Pathway

    PubMed Central

    Ye, Lilin; Zeng, Rongyu; Bai, Yu; Roopenian, Derry C.; Zhu, Xiaoping

    2011-01-01

    Vaccine strategies to prevent invasive mucosal pathogens are being sought because 80–90% of infectious diseases are initiated at mucosal surfaces. However, our ability to deliver an intact vaccine antigen across a mucosal barrier for induction of effective immunity is limited. The neonatal Fc receptor (FcRn) mediates the transport of IgG across polarized epithelial cells lining mucosal surfaces. By mimicking IgG transfer at mucosal surfaces, intranasal immunization with a model antigen, herpes simplex virus type-2 (HSV-2) glycoprotein gD fused with an IgG Fc fragment, in combination with the adjuvant CpG, resulted in complete protection of wild type, but not FcRn knockout, mice that were intravaginally challenged with virulent HSV-2 186. This immunization strategy induced efficient mucosal and systemic antibody, B and T cell immune responses, including memory immune responses, which remained stable at least 6 months post-vaccination and conferred protection for a majority of animals. These results demonstrate that the FcRn-IgG transcellular transport pathway may represent a novel mucosal vaccine delivery route for a subunit vaccine against abundant mucosal pathogens. PMID:21240266

  12. Cytomegalovirus Seroprevalence in Pregnant Women and Association with Adverse Pregnancy/Neonatal Outcomes in Jiangsu Province, China

    PubMed Central

    Chen, Jie; Xu, Biyun; Zhou, Yi-Hua; Hu, Yali

    2014-01-01

    Background In this study, we aimed to determine the provincial population-based seroprevalence in pregnant women and to further explore the association of maternal CMV infection status and adverse pregnancy/neonatal/growth outcomes in Jiangsu, China. Methods In this case-control study, the sera from 527 pregnant women with adverse pregnancy/neonatal outcomes and 496 mothers of healthy infants in Jiangsu Province, collected at gestation age of 15–20 weeks, were tested for anti-CMV IgG, IgM and IgG avidity. Adverse pregnancy/neonatal outcomes were identified based on pregnancy/neonatal outcomes. Results The overall seroprevalence of anti-CMV IgG was 98.7%, with 99.4% and 98.0% in the case and control groups, respectively (P = 0.039). The prevalence of anti-CMV IgG+/IgM+, was higher in the case group than that in the control group (3.8% vs. 1.6%, P = 0.033). Anti-CMV IgG avidity assay showed that none in the control group were primarily infected, but five (0.9%) in the case group underwent primary infection (P = 0.084); all five infants of these women presented severe adverse neonatal/growth outcomes. Exact logistic regression analysis showed that anti-CMV IgG+/IgM+ was associated with adverse pregnancy/neonatal/growth outcomes (aOR = 2.44, 95% CI 1.01–6.48, P = 0.047). Maternal low education level and prior abnormal pregnancies also were risk factors for adverse pregnancy/neonatal outcomes. Conclusions In populations with very high prevalence of latent CMV infection, active maternal CMV infection during pregnancy might be a risk factor for adverse pregnancy/neonatal outcomes. PMID:25211647

  13. A novel clinical entity, IgG4-related disease (IgG4RD): general concept and details.

    PubMed

    Umehara, Hisanori; Okazaki, Kazuichi; Masaki, Yasufumi; Kawano, Mitsuhiro; Yamamoto, Motohisa; Saeki, Takako; Matsui, Shoko; Sumida, Takayuki; Mimori, Tsuneyo; Tanaka, Yoshiya; Tsubota, Kazuo; Yoshino, Tadashi; Kawa, Shigeyuki; Suzuki, Ritsuro; Takegami, Tsutomu; Tomosugi, Naohisa; Kurose, Nozomu; Ishigaki, Yasuhito; Azumi, Atsushi; Kojima, Masaru; Nakamura, Shigeo; Inoue, Dai

    2012-02-01

    IgG4-related disease (IgG4RD) is a novel clinical disease entity characterized by elevated serum IgG4 concentration and tumefaction or tissue infiltration by IgG4-positive plasma cells. IgG4RD may be present in a certain proportion of patients with a wide variety of diseases, including Mikulicz's disease, autoimmune pancreatitis, hypophysitis, Riedel thyroiditis, interstitial pneumonitis, interstitial nephritis, prostatitis, lymphadenopathy, retroperitoneal fibrosis, inflammatory aortic aneurysm, and inflammatory pseudotumor. Although IgG4RD forms a distinct, clinically independent disease category and is attracting strong attention as a new clinical entity, many questions and problems still remain to be elucidated, including its pathogenesis, the establishment of diagnostic criteria, and the role of IgG4. Here we describe the concept of IgG4RD and up-to-date information on this emerging disease entity. PMID:21881964

  14. Diagnostic performance of serum IgG4 level for IgG4-related disease: a meta-analysis.

    PubMed

    Xu, Wen-Long; Ling, Ying-Chun; Wang, Zhi-Kai; Deng, Fang

    2016-01-01

    An elevated serum IgG4 level is one of the most useful factors in the diagnosis of IgG4-related disease (IgG4-RD). In this study, we performed a meta-analysis of the published articles assessing the diagnostic accuracy of serum IgG4 concentrations for IgG4-RD. The databases of MEDLINE/PubMed, EMBASE and Web of Science were systematically searched for relevant studies. Sensitivities and specificities of serum IgG4 in each study were calculated, and the hierarchical summary receiver operating characteristic (HSROC) model with a random effects model were employed to obtain the individual and pooled estimates of sensitivities and specificities. In total, twenty-three studies comprising 6048 patients with IgG4-RD were included in the meta-analysis. The pooled sensitivity was 85% with a 95% confidence interval (CI) of 78-90%; the pooled specificity was 93% with a 95% CI of 90-95%. The HSROC curve for quantitative serum IgG4 lies closer to the upper left corner of the plot, and the area under the curve (AUC) was 0.95 (95% CI 0.93, 0.97), which suggested a high diagnostic accuracy of serum IgG4 for the entity of IgG4-RD. Our study suggests that serum IgG4 has high sensitivity and specificity in the diagnosis of IgG4-RD. PMID:27558881

  15. Diagnostic performance of serum IgG4 level for IgG4-related disease: a meta-analysis

    PubMed Central

    Xu, Wen-long; Ling, Ying-chun; Wang, Zhi-kai; Deng, Fang

    2016-01-01

    An elevated serum IgG4 level is one of the most useful factors in the diagnosis of IgG4-related disease (IgG4-RD). In this study, we performed a meta-analysis of the published articles assessing the diagnostic accuracy of serum IgG4 concentrations for IgG4-RD. The databases of MEDLINE/PubMed, EMBASE and Web of Science were systematically searched for relevant studies. Sensitivities and specificities of serum IgG4 in each study were calculated, and the hierarchical summary receiver operating characteristic (HSROC) model with a random effects model were employed to obtain the individual and pooled estimates of sensitivities and specificities. In total, twenty-three studies comprising 6048 patients with IgG4-RD were included in the meta-analysis. The pooled sensitivity was 85% with a 95% confidence interval (CI) of 78–90%; the pooled specificity was 93% with a 95% CI of 90–95%. The HSROC curve for quantitative serum IgG4 lies closer to the upper left corner of the plot, and the area under the curve (AUC) was 0.95 (95% CI 0.93, 0.97), which suggested a high diagnostic accuracy of serum IgG4 for the entity of IgG4-RD. Our study suggests that serum IgG4 has high sensitivity and specificity in the diagnosis of IgG4-RD. PMID:27558881

  16. Effect of gut active carbohydrates on plasma IgG concentrations in piglets and calves.

    PubMed

    Lazarevic, M; Spring, P; Shabanovic, M; Tokic, V; Tucker, L A

    2010-06-01

    Improving immune status in neonates is crucial to health and production. Gut active carbohydrates (GAC) have been associated with increasing immunoglobin levels and immonucompetence development in mammals. The objective of the following studies was to evaluate whether GAC (mannan-oligosaccharides) applied orally to progeny immediately following parturition, improved blood plasma immunoglobulin (Ig) type G concentrations in piglets and calves. Three trials were conducted comparing control groups with those receiving GAC orally. The first two trials used piglets that were monitored for blood IgG at 2 days of age and for changes in body weight (BW), and the third trial monitored calf IgG from birth to 21 days of age. Piglets in the experimental group received 0.75 g GAC in 10 ml saline at birth and 24 h of age. The calf trial compared the control group against calves that received 22.5 g GAC mixed into 4.5 l of colostrum (to give 5 g/l) in the first 24 h after parturition. Blood serum samples were taken at 2 days post partum in piglets, and at several time points from 6 h to 21 days of age in calves, and were analysed for IgG levels by radial immunodiffusion. In the first piglet trial, significantly higher levels (32%) of IgG were observed for piglets fed GAC (P < 0.001), and in the second, IgG concentration was elevated by 23% (P < 0.01) and BW increased by 9% (P = 0.023) with GAC supplementation. Significant improvements for calves were recorded at all time points in those fed GAC (P < 0.05), with an increase in serum IgG observed after the first day, which was maintained throughout the sampling period, resulting in a difference of 39% at the end of the trial (21 d). These findings form a basis for further studies, which are required to investigate possible modes of action involved in enhancing blood immunoglobulin concentrations in young animals, and the longer-term effects this may have on the development of the immune response. PMID:22444266

  17. VapA-specific IgG and IgG subclasses responses after natural infection and experimental challenge of foals with Rhodococcus equi.

    PubMed

    Sanz, M G; Villarino, N; Ferreira-Oliveira, A; Horohov, D W

    2015-03-15

    Rhodococcus equi is a common cause of pneumonia in young foals worldwide and has considerable economic effects on the global equine industry. Despite ongoing efforts, no vaccine is currently available to prevent rhodococaal pneumonia. This is due, in part, to an incomplete understanding of the protective immune response to this bacterium. While antibodies to VapA, a lipoprotein produced by virulent R. equi, are useful in differentiating antibody production in response to pathogenic versus non-pathogenic strains, the significance of the humoral response of foals to this lipoprotein remains poorly defined. The objectives of this study were to evaluate changes in VapA-specific IgG and IgG subclasses after exposure and infection of neonatal foals. Experimental foals included those challenged with R. equi at 1 (n=18), 2 (n=4) and 3 (n=6) weeks of age. Confirmed naturally infected (n=7) and not infected (n=3) foals were also included. All foals were bled 24h after birth and weekly thereafter for a period of 8 weeks. Antibody changes over time were evaluated. Following birth, VapA-specific IgGs significantly (p<0.05) decreased over time in all foals as a result of normal decay of passively transferred antibodies. Both VapA-specific IgGa and IgG(T) significantly increased (p<0.05) after experimental challenge, however, the rise in IgG(T) occurred earlier. Only a significant (p<0.05) increase in VapA-specific IgG(T) over time was seen after natural infection. Whether VapA-specific IgG(T) can be used to differentiate rhodococcal from other pneumonias requires further investigation under field conditions. PMID:25681111

  18. Primary Neonatal Diaphragmatic Abscess

    PubMed Central

    Zouari, Mohamed; Jallouli, Mohamed; Ben Thabet, Afef; Ben Dhaou, Mahdi; Gargouri, Abdellatif; Mhiri, Riadh

    2015-01-01

    Neonatal diaphragmatic abscesses are extremely rare and they usually develop by direct extension from a liver abscess. The first case of primary diaphragmatic abscess in a neonate is reported and the difficulties of diagnosing this rare entity are discussed. PMID:26023529

  19. Diagnostic Value of Serum IgG4 for IgG4-Related Disease

    PubMed Central

    Hao, Mingju; Liu, Min; Fan, Gaowei; Yang, Xin; Li, Jinming

    2016-01-01

    Abstract Many studies about serum IgG4 for the diagnosis of IgG4-related disease (IgG4-RD) have been reported. However, these studies had relatively small sample sizes and the diagnostic accuracy values varied much between them. The aim of this study was to perform a meta-analysis to evaluate the diagnostic value of serum IgG4 for IgG4-RD. We conducted a search of relevant articles using MEDLINE, EMBASE, Web of Science, SCOPUS, and Cochrane Library databases published before December 2015. Studies those assessed the diagnostic accuracy of serum IgG4 for IgG4-RD and those provided the cut-off value for serum IgG4 were included. Data were synthesized using the random-effect model. Statistical analysis was performed using STATA with the MIDAS module and Meta-DiSc 1.4 software. A total of 9 case-control studies were analyzed, which included 1235 patients with IgG4-RD and 5696 overall controls. The pooled estimate, for a cut-off value ranged from 135 to 144 mg/dL, produced a sensitivity of 87.2% (95% CI, 85.2–89.0%) and a specificity of 82.6% (95% CI, 81.6–83.6%). The positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were 6.48 (95% CI, 3.98–10.57), 0.14 (95% CI, 0.09–0.21), and 45.15 (95% CI, 23.41–87.06), respectively. The area under the curve (AUC) of the summary receiver operating characteristic curve (SROC) was 0.94 (0.92–0.96). When a cut-off value of 2-fold the upper limit of normal was used (ranged from 270 to 280 mg/dL), the pooled sensitivity was 63% (95% CI, 60.0–66.0%), and the specificity was 94.8% (95% CI, 94.1–95.4%). The PLR, NLR, and DOR were 13.3 (95% CI, 7.39–24.0), 0.41 (95% CI, 0.29–0.58) and 33.42 (95% CI, 13.88–80.43), respectively. The AUC of the SROC was 0.92 (0.90–0.94). Only a relatively small number of studies were included, and significant heterogeneity was observed in this meta-analysis. Serum IgG4 is a modestly effective marker to diagnose IgG4-RD. Doubling the cut

  20. Management of a pregnant woman with common variable immunodeficiency and previous reactions to intravenous IgG administration

    PubMed Central

    Danieli, Maria Giovanna; Moretti, Romina; Pettinari, Lucia; Gambini, Simona

    2012-01-01

    Common variable immunodeficiency is the most common symptomatic primary immunodeficiency in adulthood. Pregnant women with common variable immunodeficiency have different needs from other patients with the same disease. Because of immature state of the fetal and neonatal immune system, transplacental transfer of immunoglobulin G (IgG) has a relevant role in protecting the infant. We here report on a high-risk pregnant woman with common variable immunodeficiency with adverse reactions to intravenous immunoglobulin that was successfully rescued with a new Ig human intravenous, 10% liquid preparation. The treatment was tailored to the health status and characteristics of the patient. The new product was safe and well tolerated. The mother did not report any infections during pregnancy and the baby had a healthy course with ‘protective’ serum IgG levels. Our case is a further demonstration that intravenous immunoglobulin tolerability in patients with immunodeficiency could be linked to a product's characteristics. PMID:23257273

  1. Management of a pregnant woman with common variable immunodeficiency and previous reactions to intravenous IgG administration.

    PubMed

    Danieli, Maria Giovanna; Moretti, Romina; Pettinari, Lucia; Gambini, Simona

    2012-01-01

    Common variable immunodeficiency is the most common symptomatic primary immunodeficiency in adulthood. Pregnant women with common variable immunodeficiency have different needs from other patients with the same disease. Because of immature state of the fetal and neonatal immune system, transplacental transfer of immunoglobulin G (IgG) has a relevant role in protecting the infant. We here report on a high-risk pregnant woman with common variable immunodeficiency with adverse reactions to intravenous immunoglobulin that was successfully rescued with a new Ig human intravenous, 10% liquid preparation. The treatment was tailored to the health status and characteristics of the patient. The new product was safe and well tolerated. The mother did not report any infections during pregnancy and the baby had a healthy course with 'protective' serum IgG levels. Our case is a further demonstration that intravenous immunoglobulin tolerability in patients with immunodeficiency could be linked to a product's characteristics. PMID:23257273

  2. Phase transitions in human IgG solutions

    PubMed Central

    Wang, Ying; Lomakin, Aleksey; Latypov, Ramil F.; Laubach, Jacob P.; Hideshima, Teru; Richardson, Paul G.; Munshi, Nikhil C.; Anderson, Kenneth C.; Benedek, George B.

    2013-01-01

    Protein condensations, such as crystallization, liquid-liquid phase separation, aggregation, and gelation, have been observed in concentrated antibody solutions under various solution conditions. While most IgG antibodies are quite soluble, a few outliers can undergo condensation under physiological conditions. Condensation of IgGs can cause serious consequences in some human diseases and in biopharmaceutical formulations. The phase transitions underlying protein condensations in concentrated IgG solutions is also of fundamental interest for the understanding of the phase behavior of non-spherical protein molecules. Due to the high solubility of generic IgGs, the phase behavior of IgG solutions has not yet been well studied. In this work, we present an experimental approach to study IgG solutions in which the phase transitions are hidden below the freezing point of the solution. Using this method, we have investigated liquid-liquid phase separation of six human myeloma IgGs and two recombinant pharmaceutical human IgGs. We have also studied the relation between crystallization and liquid-liquid phase separation of two human cryoglobulin IgGs. Our experimental results reveal several important features of the generic phase behavior of IgG solutions: (1) the shape of the coexistence curve is similar for all IgGs but quite different from that of quasi-spherical proteins; (2) all IgGs have critical points located at roughly the same protein concentration at ∼100 mg/ml while their critical temperatures vary significantly; and (3) the liquid-liquid phase separation in IgG solutions is metastable with respect to crystallization. These features of phase behavior of IgG solutions reflect the fact that all IgGs have nearly identical molecular geometry but quite diverse net inter-protein interaction energies. This work provides a foundation for further experimental and theoretical studies of the phase behavior of generic IgGs as well as outliers with large propensity to

  3. Phase transitions in human IgG solutions

    NASA Astrophysics Data System (ADS)

    Wang, Ying; Lomakin, Aleksey; Latypov, Ramil F.; Laubach, Jacob P.; Hideshima, Teru; Richardson, Paul G.; Munshi, Nikhil C.; Anderson, Kenneth C.; Benedek, George B.

    2013-09-01

    Protein condensations, such as crystallization, liquid-liquid phase separation, aggregation, and gelation, have been observed in concentrated antibody solutions under various solution conditions. While most IgG antibodies are quite soluble, a few outliers can undergo condensation under physiological conditions. Condensation of IgGs can cause serious consequences in some human diseases and in biopharmaceutical formulations. The phase transitions underlying protein condensations in concentrated IgG solutions is also of fundamental interest for the understanding of the phase behavior of non-spherical protein molecules. Due to the high solubility of generic IgGs, the phase behavior of IgG solutions has not yet been well studied. In this work, we present an experimental approach to study IgG solutions in which the phase transitions are hidden below the freezing point of the solution. Using this method, we have investigated liquid-liquid phase separation of six human myeloma IgGs and two recombinant pharmaceutical human IgGs. We have also studied the relation between crystallization and liquid-liquid phase separation of two human cryoglobulin IgGs. Our experimental results reveal several important features of the generic phase behavior of IgG solutions: (1) the shape of the coexistence curve is similar for all IgGs but quite different from that of quasi-spherical proteins; (2) all IgGs have critical points located at roughly the same protein concentration at ˜100 mg/ml while their critical temperatures vary significantly; and (3) the liquid-liquid phase separation in IgG solutions is metastable with respect to crystallization. These features of phase behavior of IgG solutions reflect the fact that all IgGs have nearly identical molecular geometry but quite diverse net inter-protein interaction energies. This work provides a foundation for further experimental and theoretical studies of the phase behavior of generic IgGs as well as outliers with large propensity to

  4. Human IgG4: a structural perspective

    PubMed Central

    Davies, Anna M; Sutton, Brian J

    2015-01-01

    IgG4, the least represented human IgG subclass in serum, is an intriguing antibody with unique biological properties, such as the ability to undergo Fab-arm exchange and limit immune complex formation. The lack of effector functions, such as antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity, is desirable for therapeutic purposes. IgG4 plays a protective role in allergy by acting as a blocking antibody, and inhibiting mast cell degranulation, but a deleterious role in malignant melanoma, by impeding IgG1-mediated anti-tumor immunity. These findings highlight the importance of understanding the interaction between IgG4 and Fcγ receptors. Despite a wealth of structural information for the IgG1 subclass, including complexes with Fcγ receptors, and structures for intact antibodies, high-resolution crystal structures were not reported for IgG4-Fc until recently. Here, we highlight some of the biological properties of human IgG4, and review the recent crystal structures of IgG4-Fc. We discuss the unexpected conformations adopted by functionally important Cγ2 domain loops, and speculate about potential implications for the interaction between IgG4 and FcγRs. PMID:26497518

  5. Oral Lesions in Neonates

    PubMed Central

    Rao, Roopa S; Majumdar, Barnali; Jafer, Mohammed; Maralingannavar, Mahesh; Sukumaran, Anil

    2016-01-01

    ABSTRACT Oral lesions in neonates represent a wide range of diseases often creating apprehension and anxiety among parents. Early examination and prompt diagnosis can aid in prudent management and serve as baseline against the future course of the disease. The present review aims to enlist and describe the diagnostic features of commonly encountered oral lesions in neonates. How to cite this article: Patil S, Rao RS, Majumdar B, Jafer M, Maralingannavar M, Sukumaran A. Oral Lesions in Neonates. Int J Clin Pediatr Dent 2016;9(2):131-138. PMID:27365934

  6. Oral Lesions in Neonates.

    PubMed

    Patil, Shankargouda; Rao, Roopa S; Majumdar, Barnali; Jafer, Mohammed; Maralingannavar, Mahesh; Sukumaran, Anil

    2016-01-01

    Oral lesions in neonates represent a wide range of diseases often creating apprehension and anxiety among parents. Early examination and prompt diagnosis can aid in prudent management and serve as baseline against the future course of the disease. The present review aims to enlist and describe the diagnostic features of commonly encountered oral lesions in neonates. How to cite this article: Patil S, Rao RS, Majumdar B, Jafer M, Maralingannavar M, Sukumaran A. Oral Lesions in Neonates. Int J Clin Pediatr Dent 2016;9(2):131-138. PMID:27365934

  7. The different effector function capabilities of the seven equine IgG subclasses have implications for vaccine strategies.

    PubMed

    Lewis, Melanie J; Wagner, Bettina; Woof, Jenny M

    2008-02-01

    Recombinant versions of the seven equine IgG subclasses were expressed in CHO cells. All assembled into intact immunoglobulins stabilised by disulphide bridges, although, reminiscent of human IgG4, a small proportion of equine IgG4 and IgG7 were held together by non-covalent bonds alone. All seven IgGs were N-glycosylated. In addition IgG3 appeared to be O-glycosylated and could bind the lectin jacalin. Staphylococcal protein A displayed weak binding for the equine IgGs in the order: IgG1>IgG3>IgG4>IgG7>IgG2=IgG5>IgG6. Streptococcal protein G bound strongly to IgG1, IgG4 and IgG7, moderately to IgG3, weakly to IgG2 and IgG6, and not at all to IgG5. Analysis of antibody effector functions revealed that IgG1, IgG3, IgG4, IgG5 and IgG7, but not IgG2 and IgG6, were able to elicit a strong respiratory burst from equine peripheral blood leukocytes, predicting that the former five IgG subclasses are able to interact with Fc receptors on effector cells. IgG1, IgG3, IgG4 and IgG7, but not IgG2, IgG5 and IgG6, were able to bind complement C1q and activate complement via the classical pathway. The differential effector function capabilities of the subclasses suggest that, for maximum efficacy, equine vaccine strategies should seek to elicit antibody responses of the IgG1, IgG3, IgG4, and IgG7 subclasses. PMID:17669496

  8. [Neonatal herpes simplex infection].

    PubMed

    van Ham-Borawitz, V E J; Stam, E D; Welborn, K M; Sas, T C J

    2016-01-01

    Neonatal encephalitis caused by herpes simplex virus (HSV) is a familiar disease with a high mortality and morbidity rate. Isolated skin-eye-mouth infection is less familiar among professionals. In this article we present two neonates with an isolated skin lesion caused by an HSV infection. Of the neonates infected with HSV, 40-45% show isolated skin-eye-mouth disease. With correct treatment, the risk of spread to the central nervous system will decrease from 50-60% to 5-10%. Typical HSV skin lesions may present at a late stage of the disease or may be masked by a secondary bacterial infection. When a neonate presents with atypical skin lesions starting 7-12 days after the birth, immediate testing for HSV and immediate treatment are required, to decrease the risk of further progression of the disease. PMID:27122069

  9. Neonatal pain management

    PubMed Central

    Bhalla, Tarun; Shepherd, Ed; Tobias, Joseph D.

    2014-01-01

    The past 2-3 decades have seen dramatic changes in the approach to pain management in the neonate. These practices started with refuting previously held misconceptions regarding nociception in preterm infants. Although neonates were initially thought to have limited response to painful stimuli, it was demonstrated that the developmental immaturity of the central nervous system makes the neonate more likely to feel pain. It was further demonstrated that untreated pain can have long-lasting physiologic and neurodevelopmental consequences. These concerns have resulted in a significant emphasis on improving and optimizing the techniques of analgesia for neonates and infants. The following article will review techniques for pain assessment, prevention, and treatment in this population with a specific focus on acute pain related to medical and surgical conditions. PMID:25538531

  10. Neonatal respiratory distress syndrome

    MedlinePlus

    Hyaline membrane disease (HMD); Infant respiratory distress syndrome; Respiratory distress syndrome in infants; RDS - infants ... Neonatal RDS occurs in infants whose lungs have not yet fully ... disease is mainly caused by a lack of a slippery substance in ...

  11. Neonatal abstinence syndrome

    MedlinePlus

    NAS; Neonatal abstinence symptoms ... may contribute to the severity of a baby's NAS symptoms. ... symptoms of withdrawal. Even after medical treatment for NAS is over and babies leave the hospital, they ...

  12. Maternal and neonatal tetanus.

    PubMed

    Thwaites, C Louise; Beeching, Nicholas J; Newton, Charles R

    2015-01-24

    Maternal and neonatal tetanus is still a substantial but preventable cause of mortality in many developing countries. Case fatality from these diseases remains high and treatment is limited by scarcity of resources and effective drug treatments. The Maternal and Neonatal Tetanus Elimination Initiative, launched by WHO and its partners, has made substantial progress in eliminating maternal and neonatal tetanus. Sustained emphasis on improvement of vaccination coverage, birth hygiene, and surveillance, with specific approaches in high-risk areas, has meant that the incidence of the disease continues to fall. Despite this progress, an estimated 58,000 neonates and an unknown number of mothers die every year from tetanus. As of June, 2014, 24 countries are still to eliminate the disease. Maintenance of elimination needs ongoing vaccination programmes and improved public health infrastructure. PMID:25149223

  13. Neonatal polycystic kidney disease.

    PubMed

    Verghese, Priya; Miyashita, Yosuke

    2014-09-01

    This article provides an up-to-date comprehensive review and summary on neonatal polycystic kidney disease (PKD) with emphasis on the differential diagnosis, clinical manifestations, diagnostic techniques, and potential therapeutic approaches for the major causes of neonatal PKD, namely hereditary disease, including autosomal recessive and autosomal dominant PKD and nonhereditary PKD, with particular emphasis on multicystic dysplastic kidney. A brief overview of obstructive cystic dysplasia and simple and complex cysts is also included. PMID:25155726

  14. Neonatal clinical pharmacology

    PubMed Central

    Allegaert, Karel; van de Velde, Marc; van den Anker, John

    2013-01-01

    Effective and safe drug administration in neonates should be based on integrated knowledge on the evolving physiological characteristics of the infant who will receive the drug, and the pharmacokinetics (PK) and pharmacodynamics (PD) of a given drug. Consequently, clinical pharmacology in neonates is as dynamic and diverse as the neonates we admit to our units while covariates explaining the variability are at least as relevant as median estimates. The unique setting of neonatal clinical pharmacology will be highlighted based on the hazards of simple extrapolation of maturational drug clearance when only based on ‘adult’ metabolism (propofol, paracetamol). Secondly, maturational trends are not at the same pace for all maturational processes. This will be illustrated based on the differences between hepatic and renal maturation (tramadol, morphine, midazolam). Finally, pharmacogenetics should be tailored to neonates, not just mirror adult concepts. Because of this diversity, clinical research in the field of neonatal clinical pharmacology is urgently needed, and facilitated through PK/PD modeling. In addition, irrespective of already available data to guide pharmacotherapy, pharmacovigilance is needed to recognize specific side effects. Consequently, paediatric anesthesiologists should consider to contribute to improved pharmacotherapy through clinical trial design and collaboration, as well as reporting on adverse effects of specific drugs. PMID:23617305

  15. Neonatal surgery in Africa.

    PubMed

    Chirdan, Lohfa B; Ngiloi, Petronilla J; Elhalaby, Essam A

    2012-05-01

    The management of neonatal surgical problems continues to pose considerable challenges, particularly in low-resource settings. The burden of neonatal surgical diseases in Africa is not well documented. The characteristics of some neonatal surgical problems are highlighted. Late presentation coupled with poor understanding of the milieu interior of the neonates by incompetent health care providers and poorly equipped hospitals combine to give rise to the unacceptable high morbidity and mortality in most parts of Africa. Proper training of all staff involved in neonatal health care coupled with community awareness must be vigorously pursued by all stakeholders. Various governments throughout the continent of Africa, in conjunction with international donor agencies, must not only provide an adequate budget for health care services and improve infrastructures, but must also deliberately encourage and provide funding for neonatal surgical care and research across the continent. The well-established pediatric surgical training programs, particularly in North and South Africa, should hold the moral responsibility of training all possible numbers of young surgeons from other African countries that do not have any existing pediatric surgical training programs or those countries suffering from remarkable shortage of trained pediatric surgeons. PMID:22475121

  16. Efficiency of immunoglobulin G replacement therapy in common variable immunodeficiency: correlations with clinical phenotype and polymorphism of the neonatal Fc receptor

    PubMed Central

    Gouilleux-Gruart, V; Chapel, H; Chevret, S; Lucas, M; Malphettes, M; Fieschi, C; Patel, S; Boutboul, D; Marson, M-N; Gérard, L; Lee, M; Watier, H; Oksenhendler, E

    2013-01-01

    Treatment of common variable immunodeficiency disorders (CVID) is based on replacement therapy using intravenous (i.v.) or subcutaneous (s.c.) immunoglobulin (Ig)G. Interindividual variation of IgG dose is common. A total of 380 CVID patients on stable IgG replacement from two prospective cohorts were analysed. An ‘efficiency’ index was defined as the ratio of serum IgG trough level minus IgG residual to the average weekly dose of IgG infusion. A reduced efficiency of IgG was associated independently with the i.v. route (P < 0·001) and with the presence of at least one CVID disease-related phenotype (lymphoproliferation, autoimmune cytopenia or enteropathy) (P < 0·001). High IgG efficiency was noted in patients homozygotes for the variable number tandem repeat (VNTR) 3/3 polymorphism of the neonatal Fc receptor gene [IgG Fc fragment receptor transporter alpha chain (FCGRT)] promoter, and this was particularly significant in patients treated with IVIG (P < 0.01). In a multivariate analysis, FCGRT VNTR 3/3 genotype (P = 0·008) and high serum albumin (P < 0·001) were associated independently with increased efficiency of i.v. Ig. PMID:23286945

  17. Efficiency of immunoglobulin G replacement therapy in common variable immunodeficiency: correlations with clinical phenotype and polymorphism of the neonatal Fc receptor.

    PubMed

    Gouilleux-Gruart, V; Chapel, H; Chevret, S; Lucas, M; Malphettes, M; Fieschi, C; Patel, S; Boutboul, D; Marson, M-N; Gérard, L; Lee, M; Watier, H; Oksenhendler, E

    2013-02-01

    Treatment of common variable immunodeficiency disorders (CVID) is based on replacement therapy using intravenous (i.v.) or subcutaneous (s.c.) immunoglobulin (Ig)G. Interindividual variation of IgG dose is common. A total of 380 CVID patients on stable IgG replacement from two prospective cohorts were analysed. An 'efficiency' index was defined as the ratio of serum IgG trough level minus IgG residual to the average weekly dose of IgG infusion. A reduced efficiency of IgG was associated independently with the i.v. route (P < 0·001) and with the presence of at least one CVID disease-related phenotype (lymphoproliferation, autoimmune cytopenia or enteropathy) (P < 0·001). High IgG efficiency was noted in patients homozygotes for the variable number tandem repeat (VNTR) 3/3 polymorphism of the neonatal Fc receptor gene [IgG Fc fragment receptor transporter alpha chain (FCGRT)] promoter, and this was particularly significant in patients treated with IVIG (P < 0.01). In a multivariate analysis, FCGRT VNTR 3/3 genotype (P = 0·008) and high serum albumin (P < 0·001) were associated independently with increased efficiency of i.v. Ig. PMID:23286945

  18. IgG4 disease: The great masquerader.

    PubMed

    Yadav, Divya; Liu, Xiuli; Chahal, Prabhleen

    2016-06-01

    Systemic IgG4 disease can have a wide spectrum of clinical presentation, which can mimic several other disease entities. In this report, we describe a series of two patients with IgG4-related disease who were referred to us initially with the diagnosis of acute cholecystitis and the second patient with metastatic pancreatic adenocarcinoma with peritoneal metastasis respectively. PMID:26164258

  19. IgG4-Related Disease: A Multispecialty Condition

    PubMed Central

    da Fonseca, Emanuela Pimenta; Santiago, Mittermayer Barreto

    2014-01-01

    IgG4-related disease (IgG4-RD) is a recently recognized group of conditions, characterized by tumor-like swelling of involved organs, lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, variable degrees of fibrosis, and elevated serum IgG4 concentrations. Currently IgG4-RD is recognized as a systemic condition that can affect several organs and tissues. Herein we report the case of a 34-year-old male patient who was admitted to our hospital with diffuse abdominal pain, weight loss, and painful stiffness in his neck. He had a history of tumoral mass of the left maxillary region, right palpebral ptosis with protrusion of the eyeball, and chronic dry cough for about 6 years. Laboratory tests revealed polyclonal hypergammaglobulinemia and increased serum IgG4 levels. Immunohistochemical staining of the maxillary biopsy was compatible with IgG4-RD. He had an excellent response to corticosteroid therapy. This case highlights that IgG4-RD should be included in the differential diagnosis with multisystem diseases. PMID:25506457

  20. Influence of birth order, birth weight, colostrum and serum immunoglobulin G on neonatal piglet survival

    PubMed Central

    2012-01-01

    Background Intake of colostrum after birth is essential to stimulate intestinal growth and function, and to provide systemic immunological protection via absorption of Immunoglobulin G (IgG). The birth order and weight of 745 piglets (from 75 litters) were recorded during a one-week period of farrowing. Only pigs weighing greater than 0.68 kg birth weight were chosen for the trial. Sow colostrum was collected during parturition, and piglets were bled between 48 and 72 hours post-birth. Piglet serum IgG and colostral IgG concentrations were determined by radial immunodiffusion. Results Sow parity had a significant (P < 0.001) effect on sow colostral IgG concentration, being 5% higher in multiparous females. Sow colostral IgG concentration explained 6% and piglet birth order accounted for another 4% of the variation observed in piglet serum IgG concentration (P < 0.05); however, birth weight had no detectable effect. Piglet serum IgG concentration had both a linear (P < 0.05) and quadratic effect (P < 0.05) on % survival. Piglets with 1,000 mg/dl serum IgG or less (n=24) had a 67% survival; whereas, piglets with IgG concentrations between 2250 to 2500 mg/dl (n=247) had a 91% survival. Birth order had no detectable effect on survival, but birth weight had a positive linear effect (P < 0.05). Piglets weighing 0.9 kg (n = 107) at birth had a 68% survival rate, and those weighing 1.6 kg (n = 158) had an 89% survival. Conclusion We found that the combination of sow colostrum IgG concentration and birth order can account for 10% of the variation of piglet serum IgG concentration and that piglets with less than 1,000 mg/dl IgG serum concentration and weight of 0.9 kg at birth had low survival rate when compared to their larger siblings. The effective management of colostrum uptake in neonatal piglets in the first 24 hrs post-birth may potentially improve survival from birth to weaning. PMID:23259926

  1. NEONATAL DESTRUCTION OF DOPAMINERGIC NEURONS

    EPA Science Inventory

    Rats treated as neonates with 6-hydroxydopamine are proposed to model the dopamine deficiency associated with Lesch-Nyhan syndrome (LNS). o understand the neurobiological basis of specific behaviors in LNS, investigations were undertaken in these neonatally lesioned rats. everal ...

  2. Mucosal IgG Levels Correlate Better with Respiratory Syncytial Virus Load and Inflammation than Plasma IgG Levels

    PubMed Central

    Vissers, Marloes; Ahout, Inge M. L.; de Jonge, Marien I.

    2015-01-01

    Maternal vaccination is currently considered a strategy against respiratory syncytial virus (RSV) infections. In RSV-infected infants, high mucosal IgG levels correlated better with reduced RSV load and lower mucosal CXCL10 levels than plasma IgG levels. For future vaccination strategies against RSV, more focus should be on the mucosal humoral immune response. PMID:26656116

  3. Immunogenicity of synthetic Rhodococcus equi virulence-associated protein peptides in neonate foals.

    PubMed

    Cauchard, Julien; Taouji, Saïd; Sevin, Corinne; Duquesne, Fabien; Bernabé, Magali; Laugier, Claire; Ballet, Jean Jacques

    2006-10-01

    Rhodococcus equi infection is considered the most common cause of pneumonia in foals less than 6 months of age. Immunization of foals and/or mares may become a procedure of choice for prevention. The present work documents the antibody response of neonate foals to R. equi virulence-associated protein (Vap) vaccine candidate peptides. A mixture of 4 R. equi (ATCC 33701) Vap peptides was selected based on their hydrophilicity and recognition by naturally acquired IgG antibodies from 13 adult horses and 33 neonate foals from France and Japan. They were combined with a water-based nanoparticular adjuvant to promote a protective immune response including both Th1 cytokine pattern and antibody response. A single intramuscular injection resulted in an IgG antibody response 30 days later, although inconsistently. In responding animals, no bias in IgG subclass distribution was observed, and antibody response was associated with enhanced serum opsonic activity. In conclusion, data indicate that synthetic Vap peptides combined with nanoparticular adjuvant were immunogenic and resulted in a significant increase in IgG antibodies against the corresponding virulent R. equi strain in a majority of foals. PMID:16782401

  4. Glycosylation pattern of anti-platelet IgG is stable during pregnancy and predicts clinical outcome in alloimmune thrombocytopenia.

    PubMed

    Sonneveld, Myrthe E; Natunen, Suvi; Sainio, Susanna; Koeleman, Carolien A M; Holst, Stephanie; Dekkers, Gillian; Koelewijn, Joke; Partanen, Jukka; van der Schoot, C Ellen; Wuhrer, Manfred; Vidarsson, Gestur

    2016-07-01

    Fetal or neonatal alloimmune thrombocytopenia (FNAIT) is a potentially life-threatening disease where fetal platelets are destroyed by maternal anti-platelet IgG alloantibodies. The clinical outcome varies from asymptomatic, to petechiae or intracranial haemorrhage, but no marker has shown reliable correlation with severity, making screening for FNAIT impractical and highly inefficient. We recently found IgG Fc-glycosylation towards platelet and red blood cell antigens to be skewed towards decreased fucosylation, increased galactosylation and sialylation. The lowered core-fucosylation increases the affinity of the pathogenic antibodies to FcγRIIIa and FcγRIIIb, and hence platelet destruction. Here we analysed the N-linked glycans of human platelet antigen (HPA)-1a specific IgG1 with mass spectrometry in large series of FNAIT cases (n = 166) including longitudinal samples (n = 26). Besides a significant decrease in Fc-fucosylation after the first pregnancy (P = 0·0124), Fc-glycosylation levels remained stable during and after pregnancy and in subsequent pregnancies. Multiple logistic regression analysis identified anti-HPA-1a -fucosylation (P = 0·006) combined with galactosylation (P = 0·021) and antibody level (P = 0·038) correlated with bleeding severity, making these parameters a feasible marker in screening for severe cases of FNAIT. PMID:27017954

  5. FcRn: The architect behind the immune and non-immune functions of IgG and albumin

    PubMed Central

    Pyzik, Michal; Rath, Timo; Lencer, Wayne I.; Baker, Kristi

    2015-01-01

    The neonatal Fc receptor (FcRn) belongs to the extensive and functionally divergent family of MHC molecules. Contrary to classical MHC family members, FcRn possesses little diversity and is unable to present antigens. Instead, through its capacity to bind IgG and albumin with high affinity at low pH, it regulates the serum half-lives of both of these proteins. In addition, FcRn plays important role in immunity at mucosal and systemic sites through both its ability to affect the lifespan of IgG as well as its participation in innate and adaptive immune responses. Even though the details of its biology are still emerging, the property of FcRn to rescue albumin and IgG from early degradation represents an attractive approach to alter the plasma half-life of pharmaceuticals. Here, we will review some of the most novel aspects of FcRn biology, both immune as well as non-immune, and provide some examples of FcRn-based therapies. PMID:25934922

  6. 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

  7. Pathogenicity and Epitope Characteristics Do Not Differ in IgG Subclass-Switched Anti-Desmoglein 3 IgG1 and IgG4 Autoantibodies in Pemphigus Vulgaris

    PubMed Central

    Ellebrecht, Christoph T.; Yu, Xiaocong; Posner, Marshall R.; Payne, Aimee S.

    2016-01-01

    Pemphigus vulgaris (PV) is characterized by IgG1 and IgG4 autoantibodies to desmoglein (Dsg) 3, causing suprabasal blistering of skin and mucous membranes. IgG4 is the dominant autoantibody subclass in PV and correlates with disease activity, whereas IgG1 can be associated with remittent disease. It is unknown if switching the same variable region between IgG4 and IgG1 directly impacts pathogenicity. Here, we tested whether three pathogenic PV monoclonal antibodies (mAbs) from three different patients demonstrate differences in antigen affinity, epitope specificity, or pathogenicity when expressed as IgG1 or IgG4. F706 anti-Dsg3 IgG4 and F779 anti-Dsg3 IgG1, previously isolated as heterohybridomas, and Px43, a monovalent anti-Dsg3/Dsg1 IgG antibody isolated by phage display, were subcloned to obtain paired sets of IgG1 and IgG4 mAbs. Using ELISA and cell surface staining assays, F706 and F779 demonstrated similar antigen binding affinities of IgG1 and IgG4, whereas Px43 showed 3- to 8-fold higher affinity of IgG4 versus IgG1 by ELISA, but identical binding affinities to human skin, perhaps due to targeting of a quaternary epitope best displayed in tissues. All 3 mAb pairs targeted the same extracellular cadherin (EC) domain on Dsg3, caused Dsg3 internalization in primary human keratinocytes, and caused suprabasal blisters in human skin at comparable doses. We conclude that switching IgG1 and IgG4 subclasses of pathogenic PV mAbs does not directly affect their antigen binding or pathogenic properties. PMID:27304671

  8. [Treatment of neonatal hyperbilirubinemia

    PubMed

    Carvalho, M D

    2001-07-01

    OBJECTIVE: To review the recent medical literature on the treatment of neonatal jaundice, focusing on practical aspects that are relevant to pediatricians and neonatologists. SOURCES: An extensive review of the related literature was performed, also including the authors clinical experience in this field of investigation. SUMMARY OF THE FINDINGS: Jaundice is very common among infants during the first days of life. Several factors such as maternal and neonatal history have to be considered before implementing treatment. Significant advances have been made in the past few years concerning the treatment of jaundiced newborn infants. This review focuses on three forms of treatment of neonatal hyperbilirubinemia: phototherapy, exchange transfusion and the use of drugs to reduce serum bilirubin concentration. CONCLUSIONS: Nowadays, the in-depth knowledge about the mechanism of action of phototherapy, the development of intensified phototherapy units and the use of drugs to reduce bilirubin formation, have contributed to significantly decrease the need for exchange transfusion. PMID:14676895

  9. 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

  10. Neonatal herpes simplex virus.

    PubMed

    Berardi, Alberto; Lugli, Licia; Rossi, Cecilia; Maria, Chiara Laguardia; Guidotti, Isotta; Gallo, Claudio; Ferrari, Fabrizio

    2011-10-01

    Herpes simplex virus is an important cause of neonatal infection, which can lead to death or long-term disabilities. Rarely in utero, the transmission frequently occurs during delivery. The disease may be disseminated, localized to the central nervous system, or involving skin, eye and/or mouth. Mortality rates markedly decreased with high-dose antiviral treatment. Diagnosis of neonatal infection is based on viral isolation from ulcerated vesicles or by scarifying mucocutaneous lesions. Recently polymerase chain reaction plays a central role for both viral detection (skin, mucosal, cerebrospinal fluid samples) and response to therapy. Vertical transmission may be decreased by prophylactic antiviral treatment. PMID:21942600

  11. Abnormal regulation of IgG production in multiple sclerosis.

    PubMed

    Goust, J M; Hogan, E L; Arnaud, P

    1982-03-01

    After stimulation with pokeweed mitogen (PWM), peripheral blood mononuclear cells (MNC) from patients with active multiple sclerosis (MS) produced significantly more IgG (8595 ng per milliliter, p less than 0.01) then MNC from normal age-matched controls (5477 ng per milliliter), whereas those tested during stable periods produced less IgG (4076 ng per milliliter, p less than 0.01). Treatment of MNC with sodium periodate (SP) generated suppressor cells for PWM-driven IgG production in normal controls and in most of the stable MS patients but in only 26% of those during active disease, in whom an increase in IgG production was often seen. This suggests a deficiency of inducible suppressor T cells associated with a supranormal B-cell response to polyclonal activation; T lymphocytes obtained from MS patients during active episodes strongly suppressed IgG production by normal B lymphocytes, whereas their B cells often produced more IgG in the presence of normal T cells. In active MS, a relative B-cell unresponsiveness to activated suppressor T cells would leave helper signals unbalanced, thus leading to increased B-cell activation, which might deplete the pool of inducible suppressor cells for IgG production. PMID:6460946

  12. Glycosylation of plasma IgG in colorectal cancer prognosis.

    PubMed

    Theodoratou, Evropi; Thaçi, Kujtim; Agakov, Felix; Timofeeva, Maria N; Štambuk, Jerko; Pučić-Baković, Maja; Vučković, Frano; Orchard, Peter; Agakova, Anna; Din, Farhat V N; Brown, Ewan; Rudd, Pauline M; Farrington, Susan M; Dunlop, Malcolm G; Campbell, Harry; Lauc, Gordan

    2016-01-01

    In this study we demonstrate the potential value of Immunoglobulin G (IgG) glycosylation as a novel prognostic biomarker of colorectal cancer (CRC). We analysed plasma IgG glycans in 1229 CRC patients and correlated with survival outcomes. We assessed the predictive value of clinical algorithms and compared this to algorithms that also included glycan predictors. Decreased galactosylation, decreased sialylation (of fucosylated IgG glycan structures) and increased bisecting GlcNAc in IgG glycan structures were strongly associated with all-cause (q < 0.01) and CRC mortality (q = 0.04 for galactosylation and sialylation). Clinical algorithms showed good prediction of all-cause and CRC mortality (Harrell's C: 0.73, 0.77; AUC: 0.75, 0.79, IDI: 0.02, 0.04 respectively). The inclusion of IgG glycan data did not lead to any statistically significant improvements overall, but it improved the prediction over clinical models for stage 4 patients with the shortest follow-up time until death, with the median gain in the test AUC of 0.08. These glycan differences are consistent with significantly increased IgG pro-inflammatory activity being associated with poorer CRC prognosis, especially in late stage CRC. In the absence of validated biomarkers to improve upon prognostic information from existing clinicopathological factors, the potential of these novel IgG glycan biomarkers merits further investigation. PMID:27302279

  13. 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

  14. 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

  15. Glycosylation of plasma IgG in colorectal cancer prognosis

    PubMed Central

    Theodoratou, Evropi; Thaçi, Kujtim; Agakov, Felix; Timofeeva, Maria N.; Štambuk, Jerko; Pučić-Baković, Maja; Vučković, Frano; Orchard, Peter; Agakova, Anna; Din, Farhat V. N.; Brown, Ewan; Rudd, Pauline M.; Farrington, Susan M.; Dunlop, Malcolm G.; Campbell, Harry; Lauc, Gordan

    2016-01-01

    In this study we demonstrate the potential value of Immunoglobulin G (IgG) glycosylation as a novel prognostic biomarker of colorectal cancer (CRC). We analysed plasma IgG glycans in 1229 CRC patients and correlated with survival outcomes. We assessed the predictive value of clinical algorithms and compared this to algorithms that also included glycan predictors. Decreased galactosylation, decreased sialylation (of fucosylated IgG glycan structures) and increased bisecting GlcNAc in IgG glycan structures were strongly associated with all-cause (q < 0.01) and CRC mortality (q = 0.04 for galactosylation and sialylation). Clinical algorithms showed good prediction of all-cause and CRC mortality (Harrell’s C: 0.73, 0.77; AUC: 0.75, 0.79, IDI: 0.02, 0.04 respectively). The inclusion of IgG glycan data did not lead to any statistically significant improvements overall, but it improved the prediction over clinical models for stage 4 patients with the shortest follow-up time until death, with the median gain in the test AUC of 0.08. These glycan differences are consistent with significantly increased IgG pro-inflammatory activity being associated with poorer CRC prognosis, especially in late stage CRC. In the absence of validated biomarkers to improve upon prognostic information from existing clinicopathological factors, the potential of these novel IgG glycan biomarkers merits further investigation. PMID:27302279

  16. 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. PMID:8135559

  17. Scrotal Swelling in the Neonate

    PubMed Central

    Basta, Amaya M.; Courtier, Jesse; Phelps, Andrew; Copp, Hillary L.; MacKenzie, John D.

    2016-01-01

    Discovery of scrotal swelling in a neonate can be a source of anxiety for parents, clinicians, and sonologists alike. This pictorial essay provides a focused review of commonly encountered scrotal masses and mimics specific to the neonatal setting. Although malignancy is a concern, it is very uncommon, as most neonatal scrotal masses are benign. Key discriminating features and management options are highlighted to improve the radiologist’s ability to diagnose neonatal scrotal conditions and guide treatment decisions. Neonatal scrotal processes ranging from common to uncommon will be discussed. PMID:25715370

  18. Different glycosylation pattern of human IgG1 and IgG3 antibodies isolated from transiently as well as permanently transfected cell lines.

    PubMed

    Vestrheim, A C; Moen, A; Egge-Jacobsen, W; Bratlie, D B; Michaelsen, T E

    2013-05-01

    The effector functions of IgG depend on the presence of carbohydrates attached to asparagine 297 in the Fc-portion. In this report, glycosylation profiles of recombinant wild-type and mutant IgG1 and IgG3 antibodies produced from three cell lines were analysed using LC-ESI-Orbitrap. Clear differences were detected between IgG1 and IgG3 glycoforms, where IgG1 generally contained fucosylated glycoforms, whilst IgG3 mainly were non-fucosylated. When using NS-0 and J558L cells for permanent transfection, IgG1 wt glycoforms differed between the two cell lines, whilst IgG3 wt glycoforms did not. Transiently transfected HEK 293E cells were used to produce IgG1 and IgG3 wt and mutants, affecting complement activation. Cell supernatants were harvested at early and late time points and analysed separately. IgGs harvested late showed simpler and less developed glycosylation structure compared to those harvested early. The IgG harvested early was slightly more effective in complement activation than those harvested late, whilst the antibody-dependent cell-mediated cytotoxicity was unaltered. Generally, the glycosylation pattern of the mutants tested, including a hinge truncate mutant of IgG3, did not differ significantly from the wild-type IgGs. The striking difference in glycosylation pattern of IgG1 compared to IgG3 therefore appears not to be due to the long hinge region of IgG3 (62 amino acids) relative to the IgG1 hinge region (15 amino acids). Furthermore, mutation variants at or near the C1q binding site showed similar glycosylation structure and difference in their complement activation activity observed earlier is thus most likely due to differences in protein structure only. PMID:23488770

  19. Phase Contrast Imaging in Neonates

    PubMed Central

    Zhong, Kai; Ernst, Thomas; Buchthal, Steve; Speck, Oliver; Anderson, Lynn; Chang, Linda

    2011-01-01

    Magnetic resonance phase images can yield superior gray and white matter contrast compared to conventional magnitude images. However, the underlying contrast mechanisms are not yet fully understood. Previous studies have been limited to high field acquisitions in adult volunteers and patients. In this study, phase imaging in the neonatal brain is demonstrated for the first time. Compared to adults, phase differences between gray and white matter are significantly reduced but not inverted in neonates with little myelination and iron deposits in their brains. The remaining phase difference between the neonatal and adult brains may be due to different macromolecule concentration in the unmyelinated brain of the neonates and thus different frequency due to water macromolecule exchange. Additionally, the susceptibility contrast from brain myelination can be separately studied in neonates during brain development. Therefore, magnetic resonance phase imaging is suggested as a novel tool to study neonatal brain development and pathologies in neonates. PMID:21232619

  20. [Recommendations for neonatal transport].

    PubMed

    Moreno Hernando, J; Thió Lluch, M; Salguero García, E; Rite Gracia, S; Fernández Lorenzo, J R; Echaniz Urcelay, I; Botet Mussons, F; Herranz Carrillo, G; Sánchez Luna, M

    2013-08-01

    During pregnancy, it is not always possible to identify maternal or foetal risk factors. Infants requiring specialised medical care are not always born in centres providing intensive care and will need to be transferred to a referral centre where intensive care can be provided. Therefore Neonatal Transport needs to be considered as part of the organisation of perinatal health care. The aim of Neonatal Transport is to transfer a newborn infant requiring intensive care to a centre where specialised resources and experience can be provided for the appropriate assessment and continuing treatment of a sick newborn infant. Intrauterine transfer is the ideal mode of transport when the birth of an infant with risk factors is diagnosed. Unfortunately, not all problems can be detected in advance with enough time to safely transfer a pregnant woman. Around 30- 50% of risk factors will be diagnosed during labour or soon after birth. Therefore, it is important to have the knowledge and resources to resuscitate and stabilise a newborn infant, as well as a specialised neonatal transport system. With this specialised transport it is possible to transfer newly born infants with the same level of care that they would receive if they had been born in a referral hospital, without increasing their risks or affecting the wellbeing of the newborn. The Standards Committee of the Spanish Society of Neonatology reviewed and updated recommendations for intrauterine transport and indications for neonatal transfer. They also reviewed organisational and logistic factors involved with performing neonatal transport. The Committee review included the type of personnel who should be involved; communication between referral and receiving hospitals; documentation; mode of transport; equipment to stabilise newly born infants; management during transfer, and admission at the referral hospital. PMID:23434016

  1. Maternal, neonatal and community factors influencing neonatal mortality in Brazil.

    PubMed

    Machado, Carla Jorge; Hill, Kenneth

    2005-03-01

    Child mortality (the mortality of children less than five years old) declined considerably in the developing world in the 1990s, but infant mortality declined less. The reductions in neonatal mortality were not impressive and, as a consequence, there is an increasing percentage of infant deaths in the neonatal period. Any further reduction in child mortality, therefore, requires an understanding of the determinants of neonatal mortality. 209,628 birth and 2581 neonatal death records for the 1998 birth cohort from the city of São Paulo, Brazil, were probabilistically matched. Data were from SINASC and SIM, Information Systems on Live Births and Deaths of Brazil. Logistic regression was used to find the association between neonatal mortality and the following risk factors: birth weight, gestational age, Apgar scores at 1 and 5 minutes, delivery mode, plurality, sex, maternal education, maternal age, number of prior losses, prenatal care, race, parity and community development. Infants of older mothers were less likely to die in the neonatal period. Caesarean delivery was not found to be associated with neonatal mortality. Low birth weight, pre-term birth and low Apgar scores were associated with neonatal death. Having a mother who lives in the highest developed community decreased the odds of neonatal death, suggesting that factors not measured in this study are behind such association. This result may also indicate that other factors over and above biological and more proximate factors could affect neonatal death. PMID:15768774

  2. Physiological changes in the peri-partum period and colostral IgG transfer in prolific D'man sheep: effects of parity and litter size.

    PubMed

    Chniter, Mohamed; Salhi, Imed; Harrabi, Hager; Khorchani, Touhami; Lainé, Anne-Lyse; Nowak, Raymond; Hammadi, Mohamed

    2016-02-01

    The aim of this work was to assess maternal and neonatal changes in plasma proteins, glucose and cortisol and to quantify the colostral immunoglobulin G (IgG) transfer in the peri-partum period in D'man sheep, a prolific breed, taking into account the parity of the ewe. The concentrations of proteins and glucose were high in the ewes on day 7 and at lambing before decreasing. Likewise, cortisol plasma concentration was maximal during the 6 h following lambing and dropped at 12 h. Protein and glucose concentrations were low in lambs at 1 h of birth after which they increased. By contrast, cortisol level was the highest during the first 12 h of birth and then decreased. The colostral IgG level was high at lambing and dropped by over 87 % from 1 to 48 h post-partum. In the newborn, the plasma IgG concentration was lowest at birth and increased rapidly during the first 24 h of birth. Parity influenced maternal physiology with multiparous ewes having the lowest concentrations of proteins, glucose, IgG and cortisol, but the highest colostrum IgG level. Accordingly, lambs born from primiparous ewes had lower protein, glucose and plasma IgG concentrations than lambs born from multiparous ewes. The main outcome of this study was that lambs born from primiparous ewes are characterized by the lowest physiological indices and this may influence their survival chance. PMID:26644226

  3. CD14 as a Mediator of the Mineralocorticoid Receptor-Dependent Anti-apolipoprotein A-1 IgG Chronotropic Effect on Cardiomyocytes.

    PubMed

    Mannic, Tiphaine; Satta, Nathalie; Pagano, Sabrina; Python, Magaly; Virzi, Julien; Montecucco, Fabrizio; Frias, Miguel A; James, Richard W; Maturana, Andres D; Rossier, Michel F; Vuilleumier, Nicolas

    2015-12-01

    In vitro and animal studies point to autoantibodies against apolipoprotein A-1 (anti-apoA-1 IgG) as possible mediators of cardiovascular (CV) disease involving several mechanisms such as basal heart rate interference mediated by a mineralocorticoid receptor-dependent L-type calcium channel activation, and a direct pro-inflammatory effect through the engagement of the toll-like receptor (TLR) 2/CD14 complex. Nevertheless, the possible implication of these receptors in the pro-arrhythmogenic effect of anti-apoA-1 antibodies remains elusive. We aimed at determining whether CD14 and TLRs could mediate the anti-apoA-1 IgG chronotropic response in neonatal rat ventricular cardiomyocytes (NRVC). Blocking CD14 suppressed anti-apoA-1 IgG binding to NRVC and the related positive chronotropic response. Anti-apoA-1 IgG alone induced the formation of a TLR2/TLR4/CD14 complex, followed by the phosphorylation of Src, whereas aldosterone alone promoted the phosphorylation of Akt by phosphatidylinositol 3-kinase (PI3K), without affecting the chronotropic response. In the presence of both aldosterone and anti-apoA-1 IgG, the localization of TLR2/TLR4/CD14 was increased in membrane lipid rafts, followed by PI3K and Src activation, leading to an L-type calcium channel-dependent positive chronotropic response. Pharmacological inhibition of the Src pathway led to the decrease of L-type calcium channel activity and abrogated the NRVC chronotropic response. Activation of CD14 seems to be a key regulator of the mineralocorticoid receptor-dependent anti-apoA-1 IgG positive chronotropic effect on NRVCs, involving relocation of the CD14/TLR2/TLR4 complex into lipid rafts followed by PI3K and Src-dependent L-type calcium channel activation. PMID:26393305

  4. Indel Group in Genomes (IGG) Molecular Genetic Markers.

    PubMed

    Toal, Ted W; Burkart-Waco, Diana; Howell, Tyson; Ron, Mily; Kuppu, Sundaram; Britt, Anne; Chetelat, Roger; Brady, Siobhan M

    2016-09-01

    Genetic markers are essential when developing or working with genetically variable populations. Indel Group in Genomes (IGG) markers are primer pairs that amplify single-locus sequences that differ in size for two or more alleles. They are attractive for their ease of use for rapid genotyping and their codominant nature. Here, we describe a heuristic algorithm that uses a k-mer-based approach to search two or more genome sequences to locate polymorphic regions suitable for designing candidate IGG marker primers. As input to the IGG pipeline software, the user provides genome sequences and the desired amplicon sizes and size differences. Primer sequences flanking polymorphic insertions/deletions are produced as output. IGG marker files for three sets of genomes, Solanum lycopersicum/Solanum pennellii, Arabidopsis (Arabidopsis thaliana) Columbia-0/Landsberg erecta-0 accessions, and S. lycopersicum/S. pennellii/Solanum tuberosum (three-way polymorphic) are included. PMID:27436831

  5. Coexistence of Acute Crescent Glomerulonephritis and IgG4-Related Kidney Disease

    PubMed Central

    Lu, Zeyuan; Yin, Jianyong; Bao, Hongda; Jiao, Qiong; Wu, Huijuan; Wu, Rui; Xue, Qin; Wang, Niansong; Zhang, Zhigang; Wang, Feng

    2016-01-01

    Introduction IgG4-related disease (IgG4-RD) is a fibroinflammatory disorder that may involve almost each organ or system. IgG4-related kidney disease (IgG4-RKD) refers to renal lesions associated with IgG4-RD. The most frequent morphological type of renal lesions is IgG4-related tubulointerstitial nephritis (IgG4-TIN) which is associated with increased IgG4-positive plasma cell infiltration and interstitial fibrosis. Case Report Herein, we present a rare case with coexisting IgG4-RKD and acute crescent glomerulonephritis with concomitant severe tubulointerstitial lesions instead of classic IgG4-TIN. Conclusion IgG4-RKD and acute crescent glomerulonephritis can occur in the same patient. This case may give us a clearer viewpoint of the disease. PMID:27504450

  6. In vivo metabolism of a monoclonal IgG cryoglobulin

    PubMed Central

    Abraham, G. N.; Waterhouse, Christine; Condemi, J. J.

    1979-01-01

    The metabolism of a monoclonal IgG cryoglobulin was studied in a patient with primary idiopathic cryoglobulinaemia under two different clinical conditions. Early in the illness, cryoprotein levels were diminished to 770 mg% by plasmapheresis and plasma disappearance assayed while serum levels of cryoprotein increased to 1100 mg%, i.e. the study was performed during a period of unstable cryoprotein synthesis. A second study was performed 1 year later when serum levels of cryoglobulin were stable at 1500 mg% which allowed a synthetic rate of 64 mg/kg of body weight per day to be computed. This was the upper limit of normal IgG synthesis. The final slopes of the plasma disappearance curves were nearly identical for both studies, indicating that the same fractional percentage of the cryoglobulin serum pool was degraded regardless of its serum level. T1/2 of 15·5 and 17·0 days were obtained when plasma levels were unstable and stable, respectively. For comparative purposes, the plasma disappearance of pooled normal IgG, IgG3 myeloma proteins and a highly aggregated IgG3 myeloma were also studied when cryoprotein levels were 1500 mg%. Normal IgG synthesis was suppressed and only 8·5 mg/kg body weight per day, but its plasma disappearance curve showed a final slope nearly identical to those for the cryoprotein, indicating that the ability to catabolize normal IgG was unimpaired. IgG3 myelomas were cleared at their normal accelerated rate, while aggregated IgG3 was totally cleared from the circulation within 2 days, indicating that the patient was able to catabolize circulating immune complexes. As controls, the catabolism of cryoprotein was shown to be identical to that of pooled normal IgG in two volunteers. The data support the concept that the build up of circulating IgG cryoprotein in the patient studied was due to an increase in cryoprotein synthesis and not to a lack of ability to catabolize it. PMID:428148

  7. Large vessel involvement by IgG4-related disease

    PubMed Central

    Perugino, Cory A.; Wallace, Zachary S.; Meyersohn, Nandini; Oliveira, George; Stone, James R.; Stone, John H.

    2016-01-01

    Abstract Objectives: IgG4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory condition that can affect multiple organs and lead to tumefactive, tissue-destructive lesions. Reports have described inflammatory aortitis and periaortitis, the latter in the setting of retroperitoneal fibrosis (RPF), but have not distinguished adequately between these 2 manifestations. The frequency, radiologic features, and response of vascular complications to B cell depletion remain poorly defined. We describe the clinical features, radiology findings, and treatment response in a cohort of 36 patients with IgG4-RD affecting large blood vessels. Methods: Clinical records of all patients diagnosed with IgG4-RD in our center were reviewed. All radiologic studies were reviewed. We distinguished between primary large blood vessel inflammation and secondary vascular involvement. Primary involvement was defined as inflammation in the blood vessel wall as a principal focus of disease. Secondary vascular involvement was defined as disease caused by the effects of adjacent inflammation on the blood vessel wall. Results: Of the 160 IgG4-RD patients in this cohort, 36 (22.5%) had large-vessel involvement. The mean age at disease onset of the patients with large-vessel IgG4-RD was 54.6 years. Twenty-eight patients (78%) were male and 8 (22%) were female. Thirteen patients (36%) had primary IgG4-related vasculitis and aortitis with aneurysm formation comprised the most common manifestation. This affected 5.6% of the entire IgG4-RD cohort and was observed in the thoracic aorta in 8 patients, the abdominal aorta in 4, and both the thoracic and abdominal aorta in 3. Three of these aneurysms were complicated by aortic dissection or contained perforation. Periaortitis secondary to RPF accounted for 27 of 29 patients (93%) of secondary vascular involvement by IgG4-RD. Only 5 patients demonstrated evidence of both primary and secondary blood vessel involvement. Of those treated with

  8. IgG4-Related Disease in a Urachal Tumor.

    PubMed

    Dum, Travis W; Zhang, Da; Lee, Eugene K

    2014-01-01

    IgG4-related disease is a newly recognized fibroinflammatory disorder that has the ability to affect nearly every organ system. It is characterized by tumefactive lesions and fibrosis and closely mimics neoplasms. Only one case of IgG4-related bladder mass has been reported in the literature, but there are no reports of IgG4-related disease in a urachal mass. Herein, we report a 26-year-old male who initially presented with symptoms of recurrent UTI. Work-up revealed a 6 cm urachal tumor, a 1.4 cm pulmonary lesion, and mediastinal lymphadenopathy; all metabolically active on PET scan and suspicious for urachal adenocarcinoma. Lung lesion fine needle aspiration and TURBT pathology revealed inflammation but no evidence of malignancy. The patient underwent a partial cystectomy and umbilectomy with pathology demonstrating dense plasmacytic cells, a high rate of immunohistochemistry staining positive for IgG4 plasma cells, a storiform pattern of fibrosis, and an obliterative phlebitis. Furthermore, the patient had an elevated serum IgG4 level of 227 mg/dL (range 2.4-121 mg/dL). IgG4-related disease is a newly recognized fibroinflammatory disorder that can mimic neoplastic processes and a high index of suspicion and accurate tissue pathology is necessary for an accurate diagnosis. PMID:25202466

  9. Estimation of anti-D IgG in red blood cell eluates using the specific radioactivity of 125I-labeled IgG: effect of unlabeled, cytophilic IgG

    SciTech Connect

    Masouredis, S.P.; Mahan, L.C.; Sudora, E.J.; Langley, J.W.; Victoria, E.J.

    1981-01-01

    The specific radioactivity of conventionally prepared 125I IgG anti-D eluates is significantly less (from 1/5 to 1/20) than that of the 125I IgG fraction used to prepare the eluate. This discrepancy is due to the release of unlabeled, cytophilic IgG from normal red blood cells during eluate preparation and does not represent an underestimation of the eluate anti-D IgG content. Cytophilic IgG content of eluates plays an important role in reducing the nonimmunologic binding of labeled antibody IgG. The results justify the assumption used in numerous studies that the specific radioactivity of 125I IgG fractions can be used to provide a valid estimate of the anti-D IgG content of eluates.

  10. IgG4-Related Lung Disease without Elevation of Serum IgG4 Level: A Case Report.

    PubMed

    Kang, Min Kyu; Cho, Yongseon; Han, Minsoo; Jung, Sun Young; Moon, Kyoung Min; Kim, Jinyoung; Kim, Ju Ri; Lee, Dong-Kyu; Park, Jun Hyung; Chung, So Hee

    2016-07-01

    Since IgG4-related pancreatitis was first reported in 2001, IgG4-related disease has been identified in other organs such as salivary gland, gallbladder, thyroid, retroperitoneum and kidney; but lung invasion is rare. A 63-year-old man presented with hemoptysis at the pulmonary clinic and chest computed tomography revealed about 4.1 cm irregular shaped mass with spiculated margin at the left upper lobe. Despite no elevation of serum IgG4 level, he was finally diagnosed as IgG4-related lung disease by transthoracic needle biopsy. After treatment with oral glucocorticoids, hemoptysis disappeared and the size of lung mass was decreased. PMID:27433179

  11. IgG4-Related Lung Disease without Elevation of Serum IgG4 Level: A Case Report

    PubMed Central

    Kang, Min Kyu; Han, Minsoo; Jung, Sun Young; Moon, Kyoung Min; Kim, Jinyoung; Kim, Ju Ri; Lee, Dong-kyu; Park, Jun Hyung; Chung, So Hee

    2016-01-01

    Since IgG4-related pancreatitis was first reported in 2001, IgG4-related disease has been identified in other organs such as salivary gland, gallbladder, thyroid, retroperitoneum and kidney; but lung invasion is rare. A 63-year-old man presented with hemoptysis at the pulmonary clinic and chest computed tomography revealed about 4.1 cm irregular shaped mass with spiculated margin at the left upper lobe. Despite no elevation of serum IgG4 level, he was finally diagnosed as IgG4-related lung disease by transthoracic needle biopsy. After treatment with oral glucocorticoids, hemoptysis disappeared and the size of lung mass was decreased. PMID:27433179

  12. Evidence that FcRn mediates the transplacental passage of maternal IgE in the form of IgG anti-IgE/IgE immune complexes

    PubMed Central

    Bundhoo, Arvin; Paveglio, Sara; Rafti, Ektor; Dhongade, Ashish; Blumberg, Richard S.; Matson, Adam P.

    2015-01-01

    Background The mechanism(s) responsible for acquisition of maternal antibody isotypes other than IgG are not fully understood. This uncertainty is a major reason underlying the continued controversy regarding whether cord blood (CB) IgE originates in the mother or fetus. Objective To investigate the capacity of maternal IgE to be transported across the placenta in the form of IgG anti-IgE/IgE immune complexes (ICs) and to determine the role of the neonatal Fc receptor (FcRn) in mediating this process. Methods Maternal and CB serum concentrations of IgE, IgG anti-IgE, and IgG anti-IgE/IgE ICs were determined in a cohort of allergic and non-allergic mother/infant dyads. Madin-Darby Canine Kidney (MDCK) cells stably transfected with human FcRn were used to study the binding and transcytosis of IgE in the form of IgG anti-IgE/IgE ICs. Results Maternal and CB serum concentrations of IgG anti-IgE/IgE ICs were highly correlated, regardless of maternal allergic status. IgG anti-IgE/IgE ICs generated in vitro bound strongly to FcRn-expressing MDCK cells and were transcytosed in an FcRn-dependent manner. Conversely, monomeric IgE did not bind to FcRn and was not transcytosed. IgE was detected in solutions of transcytosed IgG anti-IgE/IgE ICs, even though essentially all the IgE remained in complex form. Similarly, the majority of IgE in CB sera was found to be complexed to IgG. Conclusions and Clinical Relevance These data indicate that human FcRn facilitates the transepithelial transport of IgE in the form of IgG anti-IgE/IgE ICs. They also strongly suggest that the majority of IgE in CB sera is the result of FcRn-mediated transcytosis of maternal-derived IgG anti-IgE/IgE ICs. These findings challenge the widespread perception that maternal IgE does not cross the placenta. Measuring maternal or CB levels of IgG anti-IgE/IgE ICs may be a more accurate predictor of allergic risk. PMID:25652137

  13. Neonatal iliopsoas abscess.

    PubMed

    Horiuchi, Atsushi; Kameoka, Kazuhiro; Kuwabara, Jun; Watanabe, Yuji; Kawakami, Sanae; Tauchi, Hisamichi; Ishii, Eiichi

    2012-10-01

    Iliopsoas abscess (IPA) is rare in children, particularly in neonates. A male neonate was born at 38 weeks of gestation with a weight of 2915 g. On day 22 after birth, his family noticed that his right thigh was swollen. Abdominal computed tomography showed a mass extending to the right iliopsoas from the right thigh with thick septa. Puncture to the right groin yielded purulent fluid, and so a diagnosis of abscess was made. The puncture was followed by surgical drainage through a small inguinal incision, and the abscess cavity was irrigated thoroughly using normal saline. Culture of abscess fluid was positive for Streptococcus pneumoniae, so intravenous ABPC infusion was continued. The postoperative magnetic resonance imaging indicate that the IPA was derived from arthritis of the hip, and the patients received Riemenbügel for the incomplete hip dislocation. He is doing well at 2 years of age. PMID:23005905

  14. Remifentanil: applications in neonates.

    PubMed

    Kamata, Mineto; Tobias, Joseph D

    2016-06-01

    Remifentanil is a synthetic opioid derivative that was introduced into clinical practice in the United States in 1996. The unique modification of its chemical structure to include a methyl-ester ring allows its hydrolysis by non-specific plasma and tissue esterases. This molecular configuration results in its rapid metabolism thereby providing a rapid onset, easy titration by continuous infusion, and a short context-sensitive half-life with rapid elimination. These principles are stable and consistent across all age groups regardless of the infusion characteristics. Owing to these pharmacokinetic characteristics, it is an effective agent in the neonatal population allowing the provision of intense analgesia and anesthesia with a rapid recovery profile in various clinical scenarios. Here, we review the pharmacokinetics of remifentanil in neonates, discuss its clinical applications including intraoperative administration for anesthetic care, unique applications for procedural sedation including endotracheal intubation, and its potential use for sedation in the Intensive Care Unit setting during mechanical ventilation. PMID:26758072

  15. Neonatal mortality in Meerut district.

    PubMed

    Garg, S K; Mishra, V N; Singh, J V; Bhatnagar, M; Chopra, H; Singh, R B

    1993-09-01

    A study of neonatal mortality in Meerut district revealed an infant mortality rate of 50.1 per 1000 live births. Neonatal mortality accounted for 37.8% of infant mortality with a neonatal mortality rate of 19.0 per 1000 live births. 90.5% of these neonates were delivered at home largely by untrained personnel (57.2%). Only 28.6% of these neonates were treated by qualified doctors and only 30.9% of their mothers were fully immunized against tetanus. At least 2/3rd of neonatal mortality was due to exogenous factors with tetanus neonatorum and septicaemia being the principal causes of mortality each accounting for a mortality rate of 4.7 per 1000 live births. PMID:8112786

  16. [Physiopathology of neonatal hyperbilirubinemia].

    PubMed

    Vert, P

    1998-09-01

    The most important steps of bilirubin metabolism involved in the pathophysiology of neonatal hyperbilirubinemia are: 1) hemoglobin degradation by heme oxygenase; 2) bilirubin binding to serum albumin; 3) bilirubin conjugation to acid glucoronic by glucoronyl transferase. Progress in the knowledge of these metabolic steps allows to understanding of why massive hemolysis, infections, hypoxia and prematurity increase the risk of kernicterus and therefore justify adapted preventive and therapeutic measures. PMID:9789638

  17. Proteolytic components of serum IgG preparations

    PubMed Central

    Li, L; Kalaga, R; Paul, S

    2000-01-01

    Chemical catalysis, an effector mechanism utilized by fully assembled antibodies, can also be mediated by the isolated antibody subunits. Because trace amounts of free light chains (L chains) are present in IgG preparations, a detailed study was undertaken to identify the constituents responsible for the polyreactive proteolytic activity of IgG purified from human sera, determined as the extent of cleavage of the model peptide substrate Pro-Phe-Arg-methylcoumarinamide. Two proteolytic species with approximate mass of 50 kD and 150 kD were separated by repetitive gel filtration in a denaturing solvent (6 m guanidine hydrochloride). The activity of the renatured 50-kD fraction (in fluorescence units/μg protein) was more than 45-fold greater than of the 150-kD fraction. Both fractions lost the activity following immunoadsorption on immobilized anti-IgG antibody. Fab fragments prepared from the 150-kD IgG fraction retained the activity. Reducing and non-reducing SDS-electrophoresis suggested the 50-kD fraction isolated from the IgG preparations to be a mixture of heavy chain (H chain) monomers and disulphide bonded L chain dimers. Electrophoretically homogeneous monomers of 50-kD H chains and 25-kD L chains were prepared by gel filtration of reduced and alkylated IgG from seven human subjects. Each of the alkylated L chain preparations displayed the proteolytic activity. The activity in alkylated H chains was undetectable or only marginally greater than the background values. L chain dimers appear to be the major species responsible for the polyreactive proteolytic activity of serum IgG preparations, with a smaller contribution furnished by tetrameric IgG. PMID:10792374

  18. Usefulness of a commercial equine IgG test and serum protein concentration as indicators of failure of transfer of passive immunity in hospitalized foals.

    PubMed

    Metzger, Nadine; Hinchcliff, Kenneth W; Hardy, Joanne; Schwarzwald, Colin C; Wittum, Thomas

    2006-01-01

    Detection of failure of transfer of passive immunity (FTPI) is important in reducing morbidity and mortality in neonatal foals. We investigated the performance of a commercial equine IgG test (SNAP Foal IgG Test Kit) to diagnose FTPI in hospitalized foals. Furthermore, we evaluated the usefulness of serum total protein (STP) and serum globulin (SG) concentrations as indicators of FTPI. Serum IgG concentration was measured by means of the SNAP test and single radial immunodiffusion, and SG and STP concentrations were determined by means of a clinical chemistry analyzer. Subjects were 67 hospitalized foals <19 days old. The SNAP test was repeated on 37 samples from 29 foals, with identical results for 24 samples (kappa statistic, 0.64; 95% confidence interval [CI], 0.46-0.82). The sensitivity of the SNAP test to detect serum IgG concentration [IgG] < or =400 and < or =800 mg/dl was 90% (95% CI, 71-98%) and 95% (85-99%), respectively, and the specificity was 79% (71-82%) and 52% (39-57%), respectively. Sensitivity for detection of [IgG] < or =400 mg/dl was not affected (P > .05) by plasma fibrinogen concentration, sepsis score, or bacteremia. Specificity for detection of [IgG] < or = 800 mg/dl was lower (P < .05) in foals with sepsis score < or =11 (50% [31-60%] versus 100% [8-100%]) and bacteremia (25% [5-56%] versus 62% [45-62%]). Sensitivity and specificity of [STP] < or = 5.0 g/dl for [IgG] < or =800 mg/dl was 94% (83-99%) and 47% (30-56%), respectively. Performance of the SNAP test in hospitalized foals is impaired because of low specificity, but can have usefulness provided that the properties of the test and characteristics of the foal being examined are considered when interpreting the results. The STP and SG concentrations are poor sole indicators of FTPI in hospitalized foals, but may be useful adjunctive tests. PMID:16594598

  19. IgG4-unrelated type 1 autoimmune pancreatitis

    PubMed Central

    Nakano, Eriko; Kanno, Atsushi; Masamune, Atsushi; Yoshida, Naoki; Hongo, Seiji; Miura, Shin; Takikawa, Tetsuya; Hamada, Shin; Kume, Kiyoshi; Kikuta, Kazuhiro; Hirota, Morihisa; Nakayama, Keisuke; Fujishima, Fumiyoshi; Shimosegawa, Tooru

    2015-01-01

    A 50-year-old male was referred to our hospital for the evaluation of hyperproteinemia. Fluorodeoxyglucose positron emission tomography revealed high fluorodeoxyglucose uptake in the pancreas, bilateral lacrimal glands, submandibular glands, parotid glands, bilateral pulmonary hilar lymph nodes, and kidneys. Laboratory data showed an elevation of hepatobiliary enzymes, renal dysfunction, and remarkably high immunoglobulin (Ig) G levels, without elevated serum IgG4. Abdominal computed tomography revealed swelling of the pancreatic head and bilateral kidneys. Endoscopic retrograde cholangiopancreatography showed an irregular narrowing of the main pancreatic duct in the pancreatic head and stricture of the lower common bile duct. Histological examination by endoscopic ultrasonography-guided fine-needle aspiration revealed findings of lymphoplasmacytic sclerosing pancreatitis without IgG4-positive plasma cells. Abnormal laboratory values and the swelling of several organs were improved by the treatment with steroids. The patient was diagnosed as having type 1 autoimmune pancreatitis (AIP) based on the International Consensus Diagnostic Criteria. Therefore, we encountered a case of compatible type 1 AIP without elevated levels of serum IgG4 or IgG4-positive plasma cells. This case suggests that AIP phenotypes are not always associated with IgG4. PMID:26361429

  20. B-cell-independent sialylation of IgG.

    PubMed

    Jones, Mark B; Oswald, Douglas M; Joshi, Smita; Whiteheart, Sidney W; Orlando, Ron; Cobb, Brian A

    2016-06-28

    IgG carrying terminal α2,6-linked sialic acids added to conserved N-glycans within the Fc domain by the sialyltransferase ST6Gal1 accounts for the anti-inflammatory effects of large-dose i.v. Ig (IVIg) in autoimmunity. Here, B-cell-specific ablation of ST6Gal1 in mice revealed that IgG sialylation can occur in the extracellular environment of the bloodstream independently of the B-cell secretory pathway. We also discovered that secreted ST6Gal1 is produced by cells lining central veins in the liver and that IgG sialylation is powered by serum-localized nucleotide sugar donor CMP-sialic acid that is at least partially derived from degranulating platelets. Thus, antibody-secreting cells do not exclusively control the sialylation-dependent anti-inflammatory function of IgG. Rather, IgG sialylation can be regulated by the liver and platelets through the corresponding release of enzyme and sugar donor into the cardiovascular circulation. PMID:27303031

  1. Neonatal Fc receptor promoter gene polymorphism does not predict pharmacokinetics of IVIg or the clinical course of GBS.

    PubMed

    Fokkink, Willem-Jan R; Haarman, Annechien E G; Tio-Gillen, Anne P; van Rijs, Wouter; Huizinga, Ruth; van Doorn, Pieter A; Jacobs, Bart C

    2016-07-01

    Treatment of Guillain-Barré syndrome with a standard course of high-dose intravenous immunoglobulin (IVIg) results in a variable clinical recovery which is associated with changes in serum IgG levels after treatment. The neonatal Fc-receptor protects IgG from degradation, and a genetic polymorphism in its promoter region that influences the expression of Fc-receptor, may in part explain the variation in IgG levels and outcome. This polymorphism was determined by polymerase chain reaction in a cohort of 257 patients with Guillain-Barré syndrome treated with IVIg. We could not demonstrate a relation between this polymorphism, the pharmacokinetics of IVIg, or the clinical course and outcome. PMID:27386503

  2. Immunoglobulin G kappa [IgG kappa] and IgG lambda paraproteinemia in a child with AIDS and response to highly active antiretroviral therapy.

    PubMed

    Seeborg, Filiz Odabasi; Gay, Hannah; Schmiege, Lorenz M; Bernard, David; Shearer, William T

    2005-11-01

    We report an 8-year-old boy with AIDS, extremely elevated serum immunoglobulin G (IgG) concentration and IgG kappa [IgG(kappa)] and IgG lambda [IgG(lambda)] paraproteinemia. This paraproteinemia partially responded to highly active antiretroviral therapy. This case emphasizes the importance of controlling B-cell activation. PMID:16275950

  3. Schnitzler's syndrome with IgG kappa gammopathy.

    PubMed

    Akimoto, Ruri; Yoshida, Masami; Matsuda, Rie; Miyasaka, Keiichi; Itoh, Masatoshi

    2002-11-01

    A seventy-year-old man with a variant type of Schnitzler's syndrome is reported. Physical examination showed pruritic urticarial lesions on the extremities, arthralgia of knee joints, and intermittent fever. Laboratory investigations revealed a high level of IgG, an increased enythrocyte sedimentation rate, urinary Bence-Jones protein, and an M-bow in serum protein electrophoresis, which was shown to be a monoclonal IgG kappa type. Histological examination showed perivascular neutrophil and lymphocytic infiltration into the upper dermis and diffuse neutrophilic infiltration in the middle dermis. One of the clinical features of typical Schnitzler's syndrome is IgM macroglobulinemia, and this is a very rare case of this syndrome with IgG gammopathy. PMID:12484437

  4. Proliferative Glomerulonephritis with Monoclonal IgG Deposits

    PubMed Central

    Satoskar, Anjali; Markowitz, Glen S.; Valeri, Anthony M.; Appel, Gerald B.; Stokes, Michael B.; Nadasdy, Tibor; D'Agati, Vivette D.

    2009-01-01

    Dysproteinemias that result in monoclonal glomerular deposits of IgG are relatively uncommon. Here, we report the largest series of proliferative glomerulonephritis with monoclonal IgG deposits, a form of renal involvement by monoclonal gammopathy that mimics immune-complex glomerulonephritis. We retrospectively identified 37 patients, most of whom were white (81%), female (62%), or older than 50 yr (65%). At presentation, 49% had nephrotic syndrome, 68% had renal insufficiency, and 77% had hematuria. In 30% of the patients, we identified a monoclonal serum protein with the same heavy- and light-chain isotypes as the glomerular deposits (mostly IgG1 or IgG2), but only one patient had myeloma. Histologic patterns were predominantly membranoproliferative (57%) or endocapillary proliferative (35%) with membranous features. Electron microscopy revealed granular, nonorganized deposits, and immunofluorescence demonstrated glomerular deposits that stained for a single light-chain isotype and a single heavy-chain subtype, most commonly IgG3κ (53%). During an average of 30.3 mo of follow-up for 32 patients with available data, 38% had complete or partial recovery, 38% had persistent renal dysfunction, and 22% progressed to ESRD. Correlates of ESRD on univariate analysis were higher creatinine at biopsy, percentage of glomerulosclerosis, and degree of interstitial fibrosis but not immunomodulatory treatment or presence of a monoclonal spike. On multivariate analysis, higher percentage of glomerulosclerosis was the only independent predictor of ESRD. Only one patient lacking a monoclonal spike at presentation subsequently developed a monoclonal spike and no patient with a monoclonal spike at presentation subsequently developed a hematologic malignancy. We conclude that proliferative glomerulonephritis with monoclonal IgG deposits does not seem to be a precursor of myeloma in the vast majority of patients. PMID:19470674

  5. Neonatal neurosonography: A pictorial essay

    PubMed Central

    Bhat, Venkatraman; Bhat, Varun

    2014-01-01

    Neurosonography is a simple, established non-invasive technique for the intracranial assessment of preterm neonate. Apart from established indication in the evaluation of periventricular haemorrhage, it provides clue to wide range of pathology. This presentation provides a quick roadmap to the technique, imaging anatomy and spectrum of pathological imaging appearances encountered in neonates. PMID:25489132

  6. Acute Painful Ptosis Secondary to IgG4 Dacryoadenitis.

    PubMed

    Hussain, Rumana; El-Khyat, Abdul; Berry-Brincat, Antonella

    2016-01-01

    A 48-year-old lorry driver presented with 3 weeks of blurred vision, pain and diplopia. There was a right upper lid ptosis with some restriction of eye movements. A CT revealed an enlarged lacrimal gland and lacrimal gland biopsy showed IgG4-positive plasma cells. The patient responded to oral prednisolone and fully recovered. As a condition which mimics a number of diseases, an IgG4-related disease presents a diagnostic challenge and ought to be considered in both acute and chronic presentations. PMID:27293410

  7. Probiotics and colostrum/milk differentially affect neonatal humoral immune responses to oral rotavirus vaccine.

    PubMed

    Chattha, Kuldeep S; Vlasova, Anastasia N; Kandasamy, Sukumar; Esseili, Malak A; Siegismund, Christine; Rajashekara, Gireesh; Saif, Linda J

    2013-04-01

    Breast milk (colostrum [col]/milk) components and gut commensals play important roles in neonatal immune maturation, establishment of gut homeostasis and immune responses to enteric pathogens and oral vaccines. We investigated the impact of colonization by probiotics, Lactobacillus rhamnosus GG (LGG) and Bifidobacterium lactis Bb12 (Bb12) with/without col/milk (mimicking breast/formula fed infants) on B lymphocyte responses to an attenuated (Att) human rotavirus (HRV) Wa strain vaccine in a neonatal gnotobiotic pig model. Col/milk did not affect probiotic colonization in AttHRV vaccinated pigs. However, unvaccinated pigs fed col/milk shed higher numbers of probiotic bacteria in feces than non-col/milk fed colonized controls. In AttHRV vaccinated pigs, col/milk feeding with probiotic treatment resulted in higher mean serum IgA HRV antibody titers and intestinal IgA antibody secreting cell (ASC) numbers compared to col/milk fed, non-colonized vaccinated pigs. In vaccinated pigs without col/milk, probiotic colonization did not affect IgA HRV antibody titers, but serum IgG HRV antibody titers and gut IgG ASC numbers were lower, suggesting that certain probiotics differentially impact HRV vaccine responses. Our findings suggest that col/milk components (soluble mediators) affect initial probiotic colonization, and together, they modulate neonatal antibody responses to oral AttHRV vaccine in complex ways. PMID:23453730

  8. Fetal and Neonatal Arrhythmias.

    PubMed

    Jaeggi, Edgar; Öhman, Annika

    2016-03-01

    Cardiac arrhythmias are an important aspect of fetal and neonatal medicine. Premature complexes of atrial or ventricular origin are the main cause of an irregular heart rhythm. The finding is typically unrelated to an identifiable cause and no treatment is required. Tachyarrhythmia most commonly relates to supraventricular reentrant tachycardia, atrial flutter, and sinus tachycardia. Several antiarrhythmic agents are available for the perinatal treatment of tachyarrhythmias. Enduring bradycardia may result from sinus node dysfunction, complete heart block and nonconducted atrial bigeminy as the main arrhythmia mechanisms. The management and outcome of bradycardia depend on the underlying mechanism. PMID:26876124

  9. Hyperbilirubinemia in Preterm Neonates.

    PubMed

    Bhutani, Vinod K; Wong, Ronald J; Stevenson, David K

    2016-06-01

    Preterm neonates with increased bilirubin production loads are more likely to sustain adverse outcomes due to either neurotoxicity or overtreatment with phototherapy and/or exchange transfusion. Clinicians should rely on expert consensus opinions to guide timely and effective interventions until there is better evidence to refine bilirubin-induced neurologic dysfunction or benefits of bilirubin. In this article, we review the evolving evidence for bilirubin-induced brain injury in preterm infants and highlight the clinical approaches that minimize the risk of bilirubin neurotoxicity. PMID:27235203

  10. Hemolysis in Preterm Neonates.

    PubMed

    Christensen, Robert D; Yaish, Hassan M

    2016-06-01

    Hemolysis can be an important cause of hyperbilirubinemia in premature and term neonates. It can result from genetic abnormalities intrinsic to or factors exogenous to normal to red blood cells (RBCs). Hemolysis can lead to a relatively rapid increase in total serum/plasma bilirubin, hyperbilirubinemia that is somewhat slow to fall with phototherapy, or hyperbilirubinemia that is likely to rebound after phototherapy. Laboratory methods for diagnosing hemolysis are more difficult to apply, or less conclusive, in preterm infants. Transfusion of donor RBCs can present a bilirubin load that must be metabolized. Genetic causes can be identified by next-generation sequencing panels. PMID:27235204

  11. Potential Mechanisms for IgG4 Inhibition of Immediate Hypersensitivity Reactions.

    PubMed

    James, Louisa K; Till, Stephen J

    2016-03-01

    IgG4 is the least abundant IgG subclass in human serum, representing less than 5 % of all IgG. Increases in IgG4 occur following chronic exposure to antigen and are generally associated with states of immune tolerance. In line with this, IgG4 is regarded as an anti-inflammatory antibody with a limited ability to elicit effective immune responses. Furthermore, IgG4 attenuates allergic responses by inhibiting the activity of IgE. The mechanism by which IgG4 inhibits IgE-mediated hypersensitivity has been investigated using a variety of model systems leading to two proposed mechanisms. First by sequestering antigen, IgG4 can function as a blocking antibody, preventing cross-linking of receptor bound IgE. Second IgG4 has been proposed to co-stimulate the inhibitory IgG receptor FcγRIIb, which can negatively regulate FcεRI signaling and in turn inhibit effector cell activation. Recent advances in our understanding of the structural features of human IgG4 have shed light on the unique functional and immunologic properties of IgG4. The aim of this review is to evaluate our current understanding of IgG4 biology and reassess the mechanisms by which IgG4 functions to inhibit IgE-mediated allergic responses. PMID:26892721

  12. The origin of IgG production and homogeneous IgG components after allogeneic bone marrow transplantation.

    PubMed

    van Tol, M J; Gerritsen, E J; de Lange, G G; van Leeuwen, A M; Jol-van der Zijde, C M; Oudeman-Gruber, N J; de Vries, E; Radl, J; Vossen, J M

    1996-01-15

    Pediatric recipients (n = 25) of an allogeneic bone marrow (BM) graft were selected on the basis of informative IgG allotype (Gm) differences between the BM donor and the recipient. To investigate the kinetics of the appearance of IgG of donor origin and the disappearance of IgG of recipient origin, G1m and G2m allotype levels were quantified in sera obtained at regular intervals between 3 months and 5 years after BM transplantation (BMT). For this quantification, a dot immunobinding assay (DIBA) has been developed. In 19 of 22 informative recipients, the Gm allotype distribution had reached the range of values expected on the basis of the Gm phenotype of the donor within 6 months after BMT. Remarkably, IgG of recipient origin persisted in 15 of 18 informative recipients until last follow up, ie, for several years after BMT. In addition to the origin of total IgG production, the origin of homogeneous IgG components (H-IgG) appearing after BMT was investigated. H-IgG of donor origin could be detected as early as 3 weeks after BMT, but also H-IgG of recipient origin were present in 8 of 13 informative recipients for a period of up to 1 year after BMT. We conclude that host-type IgG-producing cells were not eradicated by the (myeloablative) conditioning regimen and persisted in a high number of graft recipients. It is our hypothesis that lack of graft-versus-host disease (GVHD) in the majority of these recipients results in the persistence of IgG-producing cells of host origin. These observations may be relevant for the evaluation of patients who received allogeneic BMT for the treatment of multiple myeloma. PMID:8555508

  13. Update on Neonatal Hypoglycemia

    PubMed Central

    Rozance, Paul J.

    2014-01-01

    Purpose of Review Neonatal hypoglycemia is one of the most common biochemical abnormalities encountered in the newborn. However, controversy remains surrounding its definition and management especially in asymptomatic patients. Recent Findings New information has been published that describes the incidence and timing of low glucose concentrations in the groups most at risk for asymptomatic neonatal hypoglycemia. Furthermore, one large prospective study failed to find an association between repetitive low glucose concentrations and poor neurodevelopmental outcomes in preterm infants. But hypoglycemia due to hyperinsulinism, especially genetic causes, continued to be associated with brain injury. New advances were made in the diagnosis and management of hyperinsulinism, including acquired hyperinsulinism in small for gestational age infants and others. Continuous glucose monitoring remains an attractive strategy for future research in this area. Summary The fundamental question of how best to manage asymptomatic newborns with low glucose concentrations remains unanswered. Balancing the risks of over treating newborns with low glucose concentrations who are undergoing a normal transition following birth against the risks of under treating those in whom low glucose concentrations are pathological, dangerous, and/or a harbinger of serious metabolic disease remains a challenge. PMID:24275620

  14. Neonatal Subventricular Zone Electroporation

    PubMed Central

    Feliciano, David M.; Lafourcade, Carlos A.; Bordey, Angélique

    2013-01-01

    Neural stem cells (NSCs) line the postnatal lateral ventricles and give rise to multiple cell types which include neurons, astrocytes, and ependymal cells1. Understanding the molecular pathways responsible for NSC self-renewal, commitment, and differentiation is critical for harnessing their unique potential to repair the brain and better understand central nervous system disorders. Previous methods for the manipulation of mammalian systems required the time consuming and expensive endeavor of genetic engineering at the whole animal level2. Thus, the vast majority of studies have explored the functions of NSC molecules in vitro or in invertebrates. Here, we demonstrate the simple and rapid technique to manipulate neonatal NPCs that is referred to as neonatal subventricular zone (SVZ) electroporation. Similar techniques were developed a decade ago to study embryonic NSCs and have aided studies on cortical development3,4 . More recently this was applied to study the postnatal rodent forebrain5-7. This technique results in robust labeling of SVZ NSCs and their progeny. Thus, postnatal SVZ electroporation provides a cost and time effective alternative for mammalian NSC genetic engineering. PMID:23426329

  15. Characterization of the subclasses and light chain types of IgG antibodies to rubella.

    PubMed Central

    Skvaril, F; Schilt, U

    1984-01-01

    IgG subclasses of antibodies to rubella were determined in indirect enzyme linked immunoassay (ELISA) with monoclonal antibodies specific for human IgG1, IgG2, IgG3 and IgG4. Eleven sera from women with long past history of rubella, two hyperimmune and five non-hyperimmune immunoglobulin preparations were tested. Light chain types of the antibodies were tested in ELISA with polyclonal specific antibodies to kappa and lambda chains. Antibodies to rubella in the sera as well as in the immunoglobulin preparations were found in the IgG1 subclass only. Both light chain types were present in the antibodies. PMID:6423327

  16. Ligand Valency Affects Transcytosis, Recycling and Intracellular Trafficking Mediated by the Neonatal Fc Receptor

    PubMed Central

    Tesar, Devin B; Tiangco, Noreen E; Bjorkman, Pamela J

    2006-01-01

    The neonatal Fc receptor (FcRn) transports IgG across epithelial cell barriers to provide maternal antibodies to offspring and serves as a protection receptor by rescuing endocytosed IgG and albumin from lysosomal degradation. Here we describe the generation of polarized Madin–Darby canine kidney (MDCK) cells expressing rat FcRn (rFcRn) to investigate the potential requirement for ligand bivalency in FcRn-mediated transport. The rFcRn-MDCK cells bind, internalize and bidirectionally transcytose the bivalent ligands IgG and Fc across polarized cell monolayers. However, they cannot be used to study FcRn-mediated transport of the monovalent ligand albumin, as we observe no specific binding, internalization or transcytosis of rat albumin. To address whether ligand bivalency is required for transport, the ability of rFcRn to transcytose and recycle wild-type Fc homodimers (wtFc; two FcRn-binding sites) and a heterodimeric Fc (hdFc; one FcRn-binding site) was compared. We show that ligand bivalency is not required for transcytosis or recycling, but that wtFc is transported more efficiently than hdFc, particularly at lower concentrations. We also demonstrate that hdFc and wtFc have different intracellular fates, with more hdFc than wtFc being trafficked to lysosomes and degraded, suggesting a role for avidity effects in FcRn-mediated IgG transport. PMID:17004319

  17. The neonatal Fc receptor, FcRn, as a target for drug delivery and therapy

    PubMed Central

    Sockolosky, Jonathan T.; Szoka, Francis C.

    2015-01-01

    Immunoglobulin G (IgG)-based drugs are arguably the most successful class of protein therapeutics due in part to their remarkably long blood circulation. This arises from IgG interaction with the neonatal Fc receptor, FcRn. FcRn is the central regulator of IgG and albumin homeostasis throughout life and is increasingly being recognized as an important player in autoimmune disease, mucosal immunity, and tumor immune surveillance. Various engineering approaches that hijack or disrupt the FcRn-mediated transport pathway have been devised to develop long-lasting and non-invasive protein therapeutics, protein subunit vaccines, and therapeutics for treatment of autoimmune and infectious disease. In this review, we highlight the diverse biological functions of FcRn, emerging therapeutic opportunities, as well as the associated challenges of targeting FcRn for drug delivery and disease therapy. PMID:25703189

  18. Neonates need tailored drug formulations

    PubMed Central

    Allegaert, Karel

    2013-01-01

    Drugs are very strong tools used to improve outcome in neonates. Despite this fact and in contrast to tailored perfusion equipment, incubators or ventilators for neonates, we still commonly use drug formulations initially developed for adults. We would like to make the point that drug formulations given to neonates need to be tailored for this age group. Besides the obvious need to search for active compounds that take the pathophysiology of the newborn into account, this includes the dosage and formulation. The dosage or concentration should facilitate the administration of low amounts and be flexible since clearance is lower in neonates with additional extensive between-individual variability. Formulations need to be tailored for dosage variability in the low ranges and also to the clinical characteristics of neonates. A specific focus of interest during neonatal drug development therefore is a need to quantify and limit excipient exposure based on the available knowledge of their safety or toxicity. Until such tailored vials and formulations become available, compounding practices for drug formulations in neonates should be evaluated to guarantee the correct dosing, product stability and safety. PMID:25254168

  19. Subclass specificity of the Fc receptor for human IgG on K562.

    PubMed

    Chiofalo, M S; Teti, G; Goust, J M; Trifiletti, R; La Via, M F

    1988-07-01

    The erythroleukemic cell line K562 bears a 40-kDa Fc receptor (Fc gamma RII) serologically related to and with a similar molecular weight as the Fc gamma R present on a broad range of leukocytes. The human IgG subclass specificity of the Fc gamma R on K562 was investigated using IgG aggregates of defined size, obtained from purified human myeloma proteins. The monoclonal antibody IV.3, which reacts with the Fc gamma RII present on various cell types, totally prevented binding of 125I-IgG2 trimers to K562. Experiments with radiolabeled IgG2 trimers showed that K562 cells bound a mean of 156,764 +/- 9895 molecules per cell with an association constant (Ka) of 1.8 +/- 0.7 X 10(8) M-1. Similar results were obtained with IgG3 oligomers. IgG3 and IgG2 trimers were about two- to threefold more effective in inhibiting binding of 125I-IgG2 trimers to K562 than IgG1 and IgG4 trimers. These results were confirmed by inhibition experiments using IgG monomers. The subclass specificity of the Fc gamma RII on K562 (i.e., IgG2 = IgG3 greater than IgG1 = IgG4) is quite distinct from the one reported for the Fc gamma RI and III of human cells (i.e., IgG1 = IgG3 greater than IgG4 and IgG2). PMID:2968843

  20. Enrichment of total serum IgG4 in patients with pemphigus

    PubMed Central

    Funakoshi, T.; Lunardon, L.; Ellebrecht, C.T.; Nagler, A.R.; O’Leary, C.E.; Payne, A.S.

    2013-01-01

    Summary Background Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are potentially fatal blistering diseases caused by autoantibodies targeting desmoglein (Dsg) adhesion proteins. Previous studies have shown an IgG4 > IgG1 predominance of anti-Dsg antibodies in pemphigus; however, no studies have examined total serum IgG4 levels in pemphigus. IgG4 is induced by chronic antigen stimulation, which could occur with persistent skin blistering and potentially elevate the total serum IgG4 relative to other IgG subclasses in patients with pemphigus. Objectives The primary aim of the study was to quantitate total and Dsg-specific IgG subclasses in patients with pemphigus. Methods IgG subclasses and Dsg-specific IgG1 and IgG4 were quantitated in patients with PV and PF, and in sera from age-matched controls using a subclass enzyme-linked immunosorbent assay. The effectiveness of IgG4 depletion in blocking IgG pathogenicity in PV was determined using a keratinocyte dissociation assay. Results Dsg-specific antibodies comprised a median of 7·1% and 4·2% of total IgG4 in patients with PV and PF, respectively, with eightfold and fourfold enrichment in IgG4 vs. IgG1. Total serum IgG4, but not other IgG subclasses, was enriched in patients with PV and PF compared with age-matched controls (P = 0·004 and P = 0·005, respectively). IgG4 depletion of PV sera reduced pathogenicity in a keratinocyte dissociation assay and showed that affinity-purified IgG4 is more pathogenic than other serum IgG fractions. Conclusions Dsg-specific autoantibodies are significantly enriched in IgG4, which may explain the enrichment of total serum IgG4 in some patients with pemphigus. By preferentially targeting autoimmune rather than beneficial immune antibodies, IgG4-targeted therapies may offer safer treatment options for pemphigus. PMID:22803659

  1. Bacillus species infections in neonates.

    PubMed

    Patrick, C C; Langston, C; Baker, C J

    1989-01-01

    A case of neonatal meningitis due to Bacillus cereus is presented. Postmortem histopathologic examination revealed an invasive disease involving the brain parenchyma, with a cellular composition consistent with an indolent process indicative of possible perinatally acquired infection. One other neonate from our institution with systemic disease due to a nonanthrax bacillus is described, and a review of the English-language literature since 1900 reveals four additional neonates infected with these unusual pathogens. Such Bacillus species infections are rare but should be suspected when gram-positive bacilli are noted on gram stain, especially in an immunocompromised host. PMID:2505353

  2. The Design of New Adjuvants for Mucosal Immunity to Neisseria meningitidis B in Nasally Primed Neonatal Mice for Adult Immune Response

    PubMed Central

    Ferreira, Tatiane; De Gaspari, Elizabeth

    2012-01-01

    The aim of this study was to determine the value of detoxified Shiga toxins Stx1 and Stx2 (toxoids of Escherichia coli) as mucosal adjuvants in neonatal mice for immunogenicity against the outer membrane proteins (OMPs) of Neisseria meningitidis B. Mucosal immunization has been shown to be effective for the induction of antigen-specific immune responses in both the systemic and mucosal compartments. Systemic antibody levels (IgG, IgG1, IgG2a, IgG2b, IgM, and IgA) and mucosal IgM and IgA were measured by ELISA using an N. meningitidis as an antigen. In addition, IFN-γ and IL-6 production were measured after stimulated proliferation of immune cells. Intranasal administration elicited a higher anti-OMP IgA response in both saliva and vaginal fluids. Our results suggest that both Stx1 and Stx2 toxoids are effective mucosal adjuvants for the induction of Ag-specific IgG, IgM, and IgA antibodies. The toxoids significantly enhanced the IgG and IgM response against OMPs with a potency equivalent to CT, with the response being characterized by both IgG1 and IgG2a isotypes, and increased IFN-gamma production. Additionally, bactericidal activity was induced with IgG and IgM antibodies of high avidity. These results support the use of the new toxoids as potent inducing adjuvants that are particularly suitable for mucosal immunization. PMID:22545012

  3. Juvenile Myelomonocytic Leukemia in a Premature Neonate Mimicking Neonatal Sepsis.

    PubMed

    Lee, Ming-Luen; Yen, Hsiu-Ju; Chen, Shu-Jen; Hung, Giun-Yi; Tsao, Pei-Chen; Soong, Wen-Jue

    2016-04-01

    Juvenile myelomonocytic leukemia (JMML) is a rare hematologic malignancy in children. Its presentations include anemia, thrombocytopenia, monocytosis, skin rash, marked hepatomegaly, and/or splenomegaly. Fever and respiratory involvement are common. Here, we report a case of a premature neonate with initial symptoms of respiratory distress. She gradually developed clinical manifestations of JMML that mimicked neonatal sepsis. Three weeks after birth, JMML was diagnosed. This is the first reported case of JMML presenting in a premature infant in Taiwan. PMID:24269860

  4. Transient neonatal zinc deficiency.

    PubMed

    Krieger, I; Alpern, B E; Cunnane, S C

    1986-06-01

    We report an infant who developed clinical manifestations of zinc deficiency during the first month of life although the diet was adequate for zinc and no other causes could be ascertained. The diagnosis was confirmed by low plasma-zinc concentrations and a positive response to zinc treatment. The fatty acid profile of plasma phospholipids was typical of zinc deficiency (ie, arachidonic acid was markedly decreased). The transient nature of this disorder was evident when no relapse occurred after cessation of zinc therapy and plasma-zinc and arachidonic acid concentrations remained normal. Several explanations for the development of transient neonatal zinc deficiency are offered. The observation demonstrates that occasional infants may have requirements for zinc that are beyond the intakes of the conventional RDA. PMID:3717070

  5. Neonatal sensitization to latex.

    PubMed

    Worth, J

    2000-05-01

    Babies born in delivery rooms of hospitals are exposed to latex through skin and mucous membrane contact with prepowdered latex gloves worn by midwives and doctors, and through the inhalation of latex-bound starch powder in the air of the delivery room. This paper examines the hypothesis that they are at risk for latex sensitization, and that part of the sharp increase of childhood asthma, eczema and anaphylaxis in the past 30-40 years may be linked. These possibilities seem hitherto unsuspected. In over 700 papers on latex allergy no mention of neonatal exposure to latex has been found. Even obstetric papers discussing the risks for an atopic mother (atopy - a tendency to develop allergies) do not seem to anticipate any risk for the baby, who might also be atopic. Latex allergy is primarily regarded as an occupational hazard. This paper suggests that it is a hazard for every baby handled by latex gloves at birth. PMID:10859678

  6. Neonatal pulmonary hemosiderosis.

    PubMed

    Limme, Boris; Nicolescu, Ramona; Misson, Jean-Paul

    2014-01-01

    Idiopathic pulmonary hemosiderosis (IPH) is a rare complex entity characterized clinically by acute or recurrent episodes of hemoptysis secondary to diffuse alveolar hemorrhage. The radiographic features are variable, including diffuse alveolar-type infiltrates, and interstitial reticular and micronodular patterns. We describe a 3-week-old infant presenting with hemoptysis and moderate respiratory distress. Idiopathic pulmonary hemosiderosis was the first working diagnosis at the Emergency Department and was confirmed, 2 weeks later, by histological studies (bronchoalveolar lavage). The immunosuppressive therapy by 1 mg/kg/d prednisone was immediately started, the baby returned home on steroid therapy at a dose of 0,5 mg/kg/d. The diagnosis of idiopathic pulmonary hemosiderosis should be evocated at any age, even in the neonate, when the clinical presentation (hemoptysis and abnormal radiological chest images) is strongly suggestive. PMID:25389504

  7. The different effector function capabilities of the seven equine IgG subclasses have implications for vaccine strategies

    PubMed Central

    Lewis, Melanie J.; Wagner, Bettina; Woof, Jenny M.

    2008-01-01

    Recombinant versions of the seven equine IgG subclasses were expressed in CHO cells. All assembled into intact immunoglobulins stabilised by disulphide bridges, although, reminiscent of human IgG4, a small proportion of equine IgG4 and IgG7 were held together by non-covalent bonds alone. All seven IgGs were N-glycosylated. In addition IgG3 appeared to be O-glycosylated and could bind the lectin jacalin. Staphylococcal protein A displayed weak binding for the equine IgGs in the order: IgG1 > IgG3 > IgG4 > IgG7 > IgG2 = IgG5 > IgG6. Streptococcal protein G bound strongly to IgG1, IgG4 and IgG7, moderately to IgG3, weakly to IgG2 and IgG6, and not at all to IgG5. Analysis of antibody effector functions revealed that IgG1, IgG3, IgG4, IgG5 and IgG7, but not IgG2 and IgG6, were able to elicit a strong respiratory burst from equine peripheral blood leukocytes, predicting that the former five IgG subclasses are able to interact with Fc receptors on effector cells. IgG1, IgG3, IgG4 and IgG7, but not IgG2, IgG5 and IgG6, were able to bind complement C1q and activate complement via the classical pathway. The differential effector function capabilities of the subclasses suggest that, for maximum efficacy, equine vaccine strategies should seek to elicit antibody responses of the IgG1, IgG3, IgG4, and IgG7 subclasses. PMID:17669496

  8. Nasal manifestations of IgG4-related disease: A report of two cases.

    PubMed

    Ohno, Keiko; Matsuda, Yoko; Arai, Tomio; Kimura, Yurika

    2015-12-01

    IgG4-related disease (IgG4-RD) is a recently recognized clinical disease entity characterized by elevated serum IgG4, tumefaction, tissue infiltration of IgG4-positive plasma cells and fibrosis. IgG4-RD may occur, either synchronously or metachronously, in a variety of organs throughout the body. We describe herein two representative cases of the nasal manifestations of IgG4-RD, characterized by diffuse, crusty, erosive lesions on nasal mucosa. Oral steroid administration was effective in treating these nasal manifestations. We report a decrease in IgG4 positive plasma cell infiltrates in nasal mucosa biopsy specimens after steroid therapy, demonstrating that infiltration of IgG4-positive cells is reversible. PMID:26060132

  9. Therapeutic drug monitoring in neonates.

    PubMed

    Pauwels, Steven; Allegaert, Karel

    2016-04-01

    Therapeutic drug monitoring (TDM) aims to integrate drug measurement results into clinical decision making. The basic rules apply when using TDM in neonates (aminoglycosides, vancomycin, phenobarbital, digoxin), but additional factors should also be taken into account. First, due to both pharmacokinetic variability and non-pharmacokinetic factors, the correlation between dosage and concentration is poor in neonates, but can be overcome with the use of more complex, validated dosing regimens. Second, the time to reach steady state is prolonged, especially when no loading dose is used. Consequently, the timing of TDM sampling is important in this population. Third, the target concentration may be uncertain (vancomycin) or depend on specific factors (phenobarbital during whole body cooling). Finally, because of differences in matrix composition (eg, protein, bilirubin), assay-related inaccuracies may be different in neonates. We anticipate that complex validated dosing regimens, with subsequent TDM sampling and Bayesian forecasting, are the next step in tailoring pharmacotherapy to individual neonates. PMID:26803050

  10. Mastitis in a neonatal filly

    PubMed Central

    Gilday, Rebecca; Lewis, Danyse; Lohmann, Katharina L.

    2015-01-01

    Neonatal mastitis is a rare occurrence in the horse. This report documents a case of mastitis caused by an organism within the Streptococcus dysgalactiae group in a 1-week-old Paint filly. PMID:25565717

  11. Neonatal and pediatric respiratory care

    SciTech Connect

    Koff, P.B. ); Eitzman, D.V.; Nev, J. )

    1988-01-01

    This book contains 23 chapters. Some of the titles are: Radiographic evaluations; Neonatal parenchymal diseases: physiologic development; Oxygen therapy; Pediatric parenchymal diseases; and Care of the neurologically injured child.

  12. Neonatal euthanasia: The Groningen Protocol*

    PubMed Central

    Vizcarrondo, Felipe E.

    2014-01-01

    For the past thirty years, voluntary euthanasia and physician-assisted suicide of adult patients have been common practice in the Netherlands. Neonatal euthanasia was recently legalized in the Netherlands and the Groningen Protocol (GP) was developed to regulate the practice. Supporters claim compliance with the GP criteria makes neonatal euthanasia ethically permissible. An examination of the criteria used by the Protocol to justify the euthanasia of seriously ill neonates reveals the criteria are not based on firm moral principles. The taking of the life of a seriously ill person is not the solution to the pain and suffering of the dying process. It is the role of the medical professional to care for the ailing patient with love and compassion, always preserving the person's dignity. Neonatal euthanasia is not ethically permissible. PMID:25473136

  13. Therapeutic hypothermia in neonatal asphyxia

    PubMed Central

    Cornette, L.

    2012-01-01

    Hypoxic ischemic encephalopathy is a serious condition affecting newborn infants which can result in death and disability. There is now strong clinical evidence that moderate post-asphyxial total body cooling or hypothermia in full term neonates results in long-term neuroprotection, allowing us to proclaim this innovative therapy as “standard of care.” The treatment is a time-critical emergency and should be started within 6 hours after the insult. Such requires optimal collaboration among local hospitals, transport teams and the closest neonatal intensive care unit. The technique is only safe when applied according to published clinical trial protocols, and with admission of these patients to a neonatal intensive care unit. Future studies should be aimed at optimizing the onset, duration, and depth of hypothermia. Combination of hypothermia and drugs may further improve neuroprotection in asphyxiated full term neonates. PMID:24753900

  14. Neonatal euthanasia: The Groningen Protocol.

    PubMed

    Vizcarrondo, Felipe E

    2014-11-01

    For the past thirty years, voluntary euthanasia and physician-assisted suicide of adult patients have been common practice in the Netherlands. Neonatal euthanasia was recently legalized in the Netherlands and the Groningen Protocol (GP) was developed to regulate the practice. Supporters claim compliance with the GP criteria makes neonatal euthanasia ethically permissible. An examination of the criteria used by the Protocol to justify the euthanasia of seriously ill neonates reveals the criteria are not based on firm moral principles. The taking of the life of a seriously ill person is not the solution to the pain and suffering of the dying process. It is the role of the medical professional to care for the ailing patient with love and compassion, always preserving the person's dignity. Neonatal euthanasia is not ethically permissible. PMID:25473136

  15. IgG1 deficiency exacerbates experimental autoimmune myasthenia gravis in BALB/c mice

    PubMed Central

    Huda, Ruksana; Strait, Richard T.; Tüzün, Erdem; Finkelman, Fred D.; Christadoss, Premkumar

    2015-01-01

    Myasthenia gravis is an autoimmune disease characterized by muscle weakness due to neuromuscular junction (NMJ) damage by anti-acetylcholine receptor (AChR) auto-antibodies and complement. In experimental autoimmune myasthenia gravis (EAMG), which is induced by immunization with Torpedo AChR in CFA, anti-AChR IgG2b and IgG1 are the predominant isotypes in the circulation. Complement activation by isotypes such as IgG2b plays a crucial role in EAMG pathogenesis; this suggested the possibility that IgG1, which does not activate complement through the classical pathway, may suppress EAMG. In this study, we show that AChR-immunized BALB/c mice genetically deficient for IgG1 produce higher levels of complement-activating isotypes of anti-AChR, especially IgG3 and IgG2a, and develop increased IgG3/IgG2a deposits at the NMJ, as compared to wild type (WT) BALB/c mice. Consistent with this, AChR-immunized IgG1−/− BALB/c mice lose muscle strength and muscle AChR to a greater extent than AChR-immunized WT mice. These observations demonstrate that IgG1 deficiency leads to increased severity of EAMG associated with an increase in complement activating IgG isotypes. Further studies are needed to dissect the specific role or mechanism of IgG1 in limiting EAMG and that of EAMG exacerbating role of complement activating IgG3 and IgG2a in IgG1 deficiency. PMID:25867470

  16. Recurrent Mastoiditis Mimics IgG4 Related Disease: A Potential Diagnostic Pitfall.

    PubMed

    Deshpande, Vikram; Zane, Nicolas A; Kraft, Stefan; Stone, John H; Faquin, William C

    2016-09-01

    IgG4-related disease (IgG4-RD) is a recently recognized entity that causes progressive fibrosis and formation of mass lesions. IgG4-RD can be diagnosed histologically by its hallmarks of storiform fibrosis, prominent lymphoplasmacytic infiltrate, and obliterative phlebitis, accompanied by the infiltration of excessive numbers of IgG4-positive plasma cells as well as elevations in serum IgG4 concentrations. A recent publication reported a case of IgG4-RD in the mastoid sinus, representing a new anatomic location for this disease. We report two additional cases of IgG4-RD occurring in the mastoid and causing clinical mastoiditis. The presenting symptoms were varied-tinnitus, hearing loss, and cranial nerve palsies. All three cases showed a dense lymphoplasmacytic infiltrate, storiform type fibrosis as well as elevated numbers of IgG4 positive plasma cells. The three patients responded to immunosuppressive therapy that included steroids and Rituximab. We further investigated 162 consecutive mastoiditis cases at our institution in order to determine the frequency of IgG4-RD as a previously unrecognized cause of mastoiditis. Within this latter cohort we identified nine cases of mastoiditis that had two of the histologic features of IgG4-RD, specifically storiform fibrosis and a dense lymphoplasmacytic infiltrate. Two of these cases showed >50 IgG4-positive plasma cells per high-power field with IgG4-IgG ratio of >40 %, thus fulfilling histological criteria for IgG4-RD. However, both were due to severe acute or chronic infection. In conclusion, we reaffirm IgG4 related mastoiditis as a distinct but uncommon cause of recurrent mastoiditis. The diagnosis of IgG4-related mastoiditis should be rendered with caution, and only after the exclusion of potential mimickers, particularly infection. PMID:27091207

  17. Aberrant IgG isotype generation in mice with abnormal behaviors.

    PubMed

    Kim, So-Nam; Jo, Gwang-Ho; Kim, Hyoung-Ah; Heo, Yong

    2016-01-01

    BTBR T+tf/J (BTBR) mice were recently cited as a suitable animal model for the study of autism because of their behavioral characteristics and immunological changes similar to those reported from autistic subjects. The BTBR mouse was reported to have significantly higher levels of serum IgG, brain IgG deposits and anti-brain IgG than highly social C57BL/6 mice, suggesting involvement of aberrant immune responses in the occurrence of autism. Up-regulation of IgG production was investigated here, with a focus on the pattern of IgG isotype distribution compared with that in FVB/NJ (FVB) mice, another highly social control strain. The results indicated that levels of serum IgG1, IgG2b and IgG3 in post-natal day 21 BTBR mice was significantly higher than FVB mice, regardless of sex, resulting in higher IgG1:IgG2a ratios in BTBR mice than in FVB mice (statistical significance in males). A similar outcome regarding the IgG1:IgG2a ratio was observed in culture supernatants of bone marrow cells from these hosts. A presence of brain-reactive IgG in the sera of BTBR was higher than in FVB mice; levels of brain-reactive IgG against whole brain homogenates were higher in BTBR than in FVB mice, with significant differences seen in the striatum and substantia nigra regions. Levels of IgG1 deposited in the cerebellum, cortex, hippocampus or striatum of both BTBR male and female mice were significantly higher than in FVB counterparts. Overall, these results suggest that alterations in IgG isotype production or deposition in the brain could be implicated in the aberrant immune reactivities of BTBR mice. PMID:25691089

  18. Molecular recognition of antibody (IgG) by cellular Fc receptor (FcRI).

    PubMed

    Burton, D R; Jefferis, R; Partridge, L J; Woof, J M

    1988-11-01

    Earlier studies from this and other laboratories have provided indirect evidence for the involvement of the C gamma 2 domain of human IgG in the binding of IgG to the high affinity monocyte Fc receptor (FcRI). Two approaches have been used to extend these studies and to further localize the site of interaction on human IgG. Firstly, monoclonal antibodies (MAbs) directed against different epitopes on IgG were assayed for their capacity to inhibit the binding of radiolabelled IgG to human monocytes or U937 cells. The capacity of the MAbs to interact with their respective epitopes on FcR-bound IgG was also studied using indirect radiobinding and immunofluorescence assays. Secondly, a number of IgGs from several different species and fragments of human IgGs were assayed for their ability to inhibit the binding of radiolabelled IgG to human monocytes. The amino acid sequences of those IgGs exhibiting relatively tight, intermediate or weak binding to monocyte FcRs were compared. On the basis of these studies a possible monocyte FcR-binding site on human IgG is postulated, involving the lower hinge region of IgG (residues Leu 234-Ser 239) with possible involvement of the nearby N-proximal bend and two beta-strands (Gly 316-Lys 338). PMID:2975762

  19. Performance Evaluation of the VIDAS(®) Measles IgG Assay and Its Diagnostic Value for Measuring IgG Antibody Avidity in Measles Virus Infection.

    PubMed

    Dina, Julia; Creveuil, Christian; Gouarin, Stephanie; Viron, Florent; Hebert, Amelie; Freymuth, Francois; Vabret, Astrid

    2016-01-01

    The objective of this study is primarily to compare the performance of the VIDAS(®) Measles immunoglobulin (Ig)G assay to that of two other serological assays using an immunoassay technique, Enzygnost(®) Anti-measles Virus/IgG (Siemens) and Measles IgG CAPTURE EIA(®) (Microimmune). The sensitivity and the agreement of the VIDAS(®) Measles IgG assay compared to the Enzygnost(®) Anti-measles Virus/IgG assay and the Measles IgG CAPTURE EIA(®) assay are 100%, 97.2% and 99.0%, 98.4%, respectively. The very low number of negative sera for IgG antibodies does not allow calculation of specificity. As a secondary objective, we have evaluated the ability of the VIDAS(®) Measles IgG assay to measure anti-measles virus IgG antibody avidity with the help of the VIDAS(®) CMV IgG Avidity reagent, using 76 sera from subjects with measles and 238 other sera. Different groups of populations were analyzed. In the primary infection measles group, the mean IgG avidity index was 0.16 (range of 0.07 to 0.93) compared to 0.79 (range of 0.25 to 1) in the serum group positive for IgG antibodies and negative for IgM. These data allow to define a weak anti-measles virus IgG antibody avidity as an avidity index (AI) < 0.3 and a strong avidity as an AI > 0.6. The VIDAS(®) Measles IgG assay has a performance equivalent to that of other available products. Its use, individual and quick, is well adapted to testing for anti-measles immunity in exposed subjects. PMID:27556477

  20. Performance Evaluation of the VIDAS® Measles IgG Assay and Its Diagnostic Value for Measuring IgG Antibody Avidity in Measles Virus Infection

    PubMed Central

    Dina, Julia; Creveuil, Christian; Gouarin, Stephanie; Viron, Florent; Hebert, Amelie; Freymuth, Francois; Vabret, Astrid

    2016-01-01

    The objective of this study is primarily to compare the performance of the VIDAS® Measles immunoglobulin (Ig)G assay to that of two other serological assays using an immunoassay technique, Enzygnost® Anti-measles Virus/IgG (Siemens) and Measles IgG CAPTURE EIA® (Microimmune). The sensitivity and the agreement of the VIDAS® Measles IgG assay compared to the Enzygnost® Anti-measles Virus/IgG assay and the Measles IgG CAPTURE EIA® assay are 100%, 97.2% and 99.0%, 98.4%, respectively. The very low number of negative sera for IgG antibodies does not allow calculation of specificity. As a secondary objective, we have evaluated the ability of the VIDAS® Measles IgG assay to measure anti-measles virus IgG antibody avidity with the help of the VIDAS® CMV IgG Avidity reagent, using 76 sera from subjects with measles and 238 other sera. Different groups of populations were analyzed. In the primary infection measles group, the mean IgG avidity index was 0.16 (range of 0.07 to 0.93) compared to 0.79 (range of 0.25 to 1) in the serum group positive for IgG antibodies and negative for IgM. These data allow to define a weak anti-measles virus IgG antibody avidity as an avidity index (AI) < 0.3 and a strong avidity as an AI > 0.6. The VIDAS® Measles IgG assay has a performance equivalent to that of other available products. Its use, individual and quick, is well adapted to testing for anti-measles immunity in exposed subjects. PMID:27556477

  1. Evaluation of a protocol to reduce the incidence of neonatal calf diarrhoea on dairy herds.

    PubMed

    Meganck, V; Hoflack, G; Piepers, S; Opsomer, G

    2015-01-01

    Calf diarrhoea causes substantial economic losses in cattle herds worldwide. Neonatal calves are particularly sensitive to infections with enteropathogens. The present study focused on prevention against the main infectious causes of neonatal calf diarrhoea i.e. Escherichia coli, rota- and coronavirus, and Cryptosporidium parvum. Dairy herds (n=24) with a high percentage of neonatal calves scouring (>10%) were included and calves were sampled for the presence of these four enteropathogens. To decrease diarrhoea problems among neonatal calves, a standard protocol was tested on 13 herds (treatment group) where both C. parvum and either E. coli or rota- or coronavirus were identified as being involved, the other 11 herds served as control group. The protocol consisted of 2 points of action: preventive vaccination of dams against E. coli, rota- and coronavirus, and preventive administration of halofuginone lactate to newborn calves. The average percentage of calves suffering from neonatal diarrhoea (39.7% versus 14.3%, P<0.01) and the average percentage of faecal samples positive for C. parvum (34% versus 11%, P<0.05) differed significantly between control herds and treatment herds after implementation of the protocol. No significant differences between control and treatment group were observed in the percentage of calves excreting E. coli, rotavirus and coronavirus, both before and at the end of the trial. Furthermore, risk factors potentially associated with the development of neonatal calf scours were determined. Non-significant results were obtained for the effect of the protocol on duration of diarrhoea and the effect of the colostral IgG quantity on the risk of diarrhoea. Passive immunity transfer status of the calves, measured both before the onset and at the end of the study, were non-significant between groups. PMID:25475689

  2. IgG4 but no IgG1 antibody production after intralymphatic immunotherapy with recombinant MAT-Feld1 in human.

    PubMed

    Freiberger, S N; Zehnder, M; Gafvelin, G; Grönlund, H; Kündig, T M; Johansen, P

    2016-09-01

    Allergy immunotherapy (AIT) mediates protection against allergen exposure in part due to allergen-specific antibodies. While immunization typically stimulated IgG1 and IgG2, AIT is often associated with production of IgG4. Here, twenty cat dander-sensitized patients were randomized to receive three injections of intralymphatic immunotherapy (ILIT) with MAT-Feld1 adsorbed to aluminum hydroxide or just aluminum hydroxide (placebo) in a double-blind setting (ClinicalTrials.gov NCT00718679). Whereas the clinical data, showing benefit of Mat-Feld1 ILIT was published in 2012 (Senti et al., J Allergy Clin Immunol, vol 129(5):1290-1296), the current study investigated the cat allergen-specific antibody responses. Blood was drawn prior to ILIT, as well as 1, 3, and 12 months after first ILIT. The sera were analyzed to characterize all IgG subclasses and IgE antibody responses. ILIT with MAT-Feld1 elicited high levels of total IgG that were maintained for at least 12 months. Interestingly, a strong increase in IgG4 and some increase in IgG2 were observed throughout the study, while production of cat-specific IgG1 and IgG3 was not stimulated by MAT-Feld1 ILIT. The IgE levels remained constant. PMID:27253988

  3. Association between IgG4 Autoantibody and Complement Abnormalities in Systemic Lupus Erythematosus.

    PubMed

    Pan, Qingjun; Guo, Linjie; Wu, Jing; Cai, Jun; Liao, Huanjin; Lan, Qiaofen; Peng, Yanxia; He, Yiming; Liu, Hua-Feng

    2016-01-01

    In order to investigate the association between IgG4 autoantibody and complement abnormalities in systemic lupus erythematosus (SLE), 72 newly diagnosed SLE patients, 67 rheumatoid arthritis (RA) patients, and 41 healthy normals were employed. Serum levels of antinuclear IgG4 and IgG4-specific IgM-rheumatoid factor (RF) were measured, and the correlations between serum levels of antinuclear IgG4 and several clinical parameters were analyzed. Also, the levels of IgG subclasses, C1q, and C3 deposition in lupus nephritis (LN) were detected. The results showed that serum levels of antinuclear IgG4 were higher in SLE patients relative to healthy normals (P < 0.01). Serum levels of antinuclear IgG4 in SLE patients were positively correlated with serum levels of total IgG4, albumin, and C3 (r = 0.61, P < 0.05; r = 0.40, P < 0.05; and r = 0.54, P < 0.05, resp.) and negatively correlated with 24-hour urinary protein (r = 0.49, P < 0.05). Serum levels of IgG4-specific IgM-RF were higher in RA patients than in SLE patients (P < 0.001). Also, the ratio of the deposition score for IgG4/(IgG1 + IgG2 + IgG3 + IgG4) was negatively correlated with the score for C1q and C3 deposition in LN (r = 0.34, P < 0.05; r = 0.51, P < 0.01, resp.). In summary, the IgG4 autoantibody may dampen the inflammatory response in SLE, thus maybe providing a novel therapeutic target for SLE. PMID:27597802

  4. Association between IgG4 Autoantibody and Complement Abnormalities in Systemic Lupus Erythematosus

    PubMed Central

    Guo, Linjie; Wu, Jing; Liao, Huanjin; Lan, Qiaofen; Peng, Yanxia; He, Yiming

    2016-01-01

    In order to investigate the association between IgG4 autoantibody and complement abnormalities in systemic lupus erythematosus (SLE), 72 newly diagnosed SLE patients, 67 rheumatoid arthritis (RA) patients, and 41 healthy normals were employed. Serum levels of antinuclear IgG4 and IgG4-specific IgM-rheumatoid factor (RF) were measured, and the correlations between serum levels of antinuclear IgG4 and several clinical parameters were analyzed. Also, the levels of IgG subclasses, C1q, and C3 deposition in lupus nephritis (LN) were detected. The results showed that serum levels of antinuclear IgG4 were higher in SLE patients relative to healthy normals (P < 0.01). Serum levels of antinuclear IgG4 in SLE patients were positively correlated with serum levels of total IgG4, albumin, and C3 (r = 0.61, P < 0.05; r = 0.40, P < 0.05; and r = 0.54, P < 0.05, resp.) and negatively correlated with 24-hour urinary protein (r = 0.49, P < 0.05). Serum levels of IgG4-specific IgM-RF were higher in RA patients than in SLE patients (P < 0.001). Also, the ratio of the deposition score for IgG4/(IgG1 + IgG2 + IgG3 + IgG4) was negatively correlated with the score for C1q and C3 deposition in LN (r = 0.34, P < 0.05; r = 0.51, P < 0.01, resp.). In summary, the IgG4 autoantibody may dampen the inflammatory response in SLE, thus maybe providing a novel therapeutic target for SLE. PMID:27597802

  5. IgG4 subclass antibodies impair antitumor immunity in melanoma

    PubMed Central

    Karagiannis, Panagiotis; Gilbert, Amy E.; Josephs, Debra H.; Ali, Niwa; Dodev, Tihomir; Saul, Louise; Correa, Isabel; Roberts, Luke; Beddowes, Emma; Koers, Alexander; Hobbs, Carl; Ferreira, Silvia; Geh, Jenny L.C.; Healy, Ciaran; Harries, Mark; Acland, Katharine M.; Blower, Philip J.; Mitchell, Tracey; Fear, David J.; Spicer, James F.; Lacy, Katie E.; Nestle, Frank O.; Karagiannis, Sophia N.

    2013-01-01

    Host-induced antibodies and their contributions to cancer inflammation are largely unexplored. IgG4 subclass antibodies are present in IL-10–driven Th2 immune responses in some inflammatory conditions. Since Th2-biased inflammation is a hallmark of tumor microenvironments, we investigated the presence and functional implications of IgG4 in malignant melanoma. Consistent with Th2 inflammation, CD22+ B cells and IgG4+-infiltrating cells accumulated in tumors, and IL-10, IL-4, and tumor-reactive IgG4 were expressed in situ. When compared with B cells from patient lymph nodes and blood, tumor-associated B cells were polarized to produce IgG4. Secreted B cells increased VEGF and IgG4, and tumor cells enhanced IL-10 secretion in cocultures. Unlike IgG1, an engineered tumor antigen-specific IgG4 was ineffective in triggering effector cell–mediated tumor killing in vitro. Antigen-specific and nonspecific IgG4 inhibited IgG1-mediated tumoricidal functions. IgG4 blockade was mediated through reduction of FcγRI activation. Additionally, IgG4 significantly impaired the potency of tumoricidal IgG1 in a human melanoma xenograft mouse model. Furthermore, serum IgG4 was inversely correlated with patient survival. These findings suggest that IgG4 promoted by tumor-induced Th2-biased inflammation may restrict effector cell functions against tumors, providing a previously unexplored aspect of tumor-induced immune escape and a basis for biomarker development and patient-specific therapeutic approaches. PMID:23454746

  6. Aberrant glycosylation of Igg heavy chain in multiple myeloma.

    PubMed

    Aurer, Igor; Lauc, Gordan; Dumić, Jerka; Rendić, Dubravko; Matisić, Danica; Milos, Marija; Heffer-Lauc, Marija; Flogel, Mirna; Labar, Boris

    2007-03-01

    Although the majority of eukaryotic proteins are glycosylated, there is a dearth of knowledge regarding protein sugar moieties and their changes in disease. Most multiple myeloma cases are characterized by production of monoclonal immunoglobulins (Ig). We studied galactosylation and sialylation of IgG heavy chains in 16 patients with IgG myeloma using lectin blotting and densitometry. In comparison to age and sex matched controls, galactosylation was reduced in multiple myeloma (median 317 vs. 362, range 153-410 vs. 309-447 relative units, p = 0.015, Student's t-test). Sialylation was stage dependent; samples from patients with stage IIA had lowest amounts of sialic acid, IIIA intermediate and IIIB highest (142.6 vs. 185.9 vs. 248.5 relative units, correlation coefficient r = 0.55). Both galactosylation and sialylation levels were independent of age, sex, treatment type, response to treatment, disease duration and IgG and b2 microglobulin concentration. These data indicate that multiple myeloma is characterized by aberrant immunoglobulin glycosylation. PMID:17598409

  7. Neutrophil functions and serum IgG in growing foals.

    PubMed

    Demmers, S; Johannisson, A; Gröndahl, G; Jensen-Waern, M

    2001-11-01

    The aim of this study was to investigate the phagocytic and killing capacities as well as expression of CD18 of neutrophils obtained from healthy foals from birth to age 8 months. Blood was taken from 6 Standardbred foals at 7 time-points between ages 2-56 days and thereafter once a month. For comparison, cells from 16 mature horses were evaluated. Neutrophil phagocytosis of yeast cells was assessed by flow cytometry after opsonisation with mature pooled serum, autologous serum or anti-yeast IgG. The killing capacity of the neutrophils, as indicated by the oxidative burst, was monitored by chemiluminescence. Serum IgG concentration was measured by radial immunodiffusion. In addition to clinical examination, the amount of serum amyloid A and the total leucocyte count were used as markers for infection. The phagocytic ability was impaired until age 3 weeks, when autologous serum was used as opsonin. Killing capacity was also low initially but, from 3 months onwards, chemiluminescence values were equal to or higher than in mature horses. Serum IgG decreased from 10 g/l at 2 days to 5 g/l at 2 months and then increased gradually to 10 g/l at the end of the study. These findings may in part explain the increased susceptibility to bacterial infections in young horses. PMID:11770989

  8. Granulocyte-associated IgG in neutropenic disorders

    SciTech Connect

    Cines, D.B.; Passero, F.; Guerry, D.; Bina, M.; Dusak, B.; Schreiber, A.D.

    1982-01-01

    We applied a radiolabeled antiglobulin test to a study of patients with a variety of neutropenic disorders. After defining the nature of the interaction of radiolabeled anti-IgG with the neutrophil, we studied 16 patients with neutropenia of uncertain etiology and adequate bone marrow granulocyte precursors. Twelve of these 16 patients had increased neutrophil-associated IgG (PMN-IgG). Patients with the highest levels of PMN-IgG had the lowest neutrophil counts. The majority of patients with neutropenia and increased PMN-IgG had an underlying immunologic disorder that included immune thrombocytopenic purpura in 5 patients and autoimmune hemolytic anemia in 1 patient. In some patients, elevated PMN-IgG preceded other evidence for immunologic disease. The direct antiglobulin test helped to distinguish neutropenic patients with increased PMN-IgG both from patients with neutropenia due to a known nonimmune disorder and from nonneutropenic patients with rheumatoid arthritis or systemic lupus erythematosis. Each of four patients with increased neutrophil-associated IgG treated with systemic corticosteroids responded clinically with an associated fall in neutrophil IgG and a rise in the circulating neutrophil count. The radiolabeled antiglobulin test appears useful in defining a subpopulation of patients with neutropenia due to an underlying immunologic disorder.

  9. Granulocyte-associated IgG in neutropenic disorders

    SciTech Connect

    Cines, D.B.; Passero, F.; Guerry, D. IV; Bina, M.; Dusak, B.; Schreiber, A.D

    1982-01-01

    We applied a radiolabeled antiglobulin test to a study of patients with a variety of neutropenic disorders. After defining the nature of the interaction of radiolabeled anti-IgG with the neutrophil, we studied 16 patients with neutropenia of uncertain etiology and adequate bone marrow granulocyte precursors. Twelve of these 16 patients had increased neutrophil-associated IgG (PMN-IgG). Patients with the highest levels of PMN-IgG had the lowest neutrophil counts. The majority of patients with neutropenia and increased PMN-IgG had an underlying immunologic disorder that included immune thrombocytopenic purpura in 5 patients and autoimmune hemolytic anemia in 1 patient. In some patients, elevated PMN-IgG preceded other evidence for immunologic disease. The direct antiglobulin test helped to distinguish neutropenic patients with increased PMN-IgG both from patients with neutropenia due to a known nonimmune disorder and from noneutropenic patients with rheumatoid arthritis or systemic lupus erythematosis. Each of four patients with increased neutrophil-associated IgG treated with systemic corticosteroids responded clinically with an associated fall in neutrophil IgG and a rise in the circulating neutrophil count. The radiolabeled antiglobulin test appears useful in defining a subpopulation of patients with neutropenia due to an underlying immunologic disorder.

  10. Functional Neonatal Echocardiography: Indian Experience

    PubMed Central

    Suryawanshi, Pradeep B.; Maheshwari, Rajesh; Patnaik, Suprabha; Malshe, Nandini; Kalrao, Vijay; Lalwani, Sanjay; Surwade, Jitendra

    2015-01-01

    Introduction Functional echocardiography, as opposed to echocardiography as performed by the cardiologist, is the bedside utilization of cardiac ultrasound to take after functional and haemodynamic changes longitudinally. Information reflecting cardiovascular capacity and systemic and pulmonary blood flow in sick preterm and term neonates can be observed utilizing this strategy. Information is lacking on its use in neonatal units in India. Aim To characterize the impact of Functional neonatal echocardiography (FnECHO) programme on decision making in a tertiary care centre in India by evaluating its frequency of use, patient characteristics, and indications. Materials and Methods Prospective observational study of neonates in a tertiary Neonatal Intensive Care Unit (NICU) in Pune (India) from February 2014 to January 2015. All the neonates undergoing FnECHO during this 12 month period based on clinical findings were included in the study. Data extracted from the review of the clinical notes included gestational age, birth-weight, mode of delivery, Apgar scores, details of respiratory and cardiovascular support, timing of FnECHO and any other clinical diagnosis. The findings of echocardiography were recorded and correlated with the clinical and other laboratory or X-ray findings. If these findings indicated a change in management, it was instituted. Results A total of 348 echocardiographic studies were performed in 187 neonates (mean 1.86; SD 2.02). The most frequent indication was Patent Ductus Arteriosus (PDA) assessment (n= 174, 50%), followed by haemodynamic instability (n=43, 12.36%). The results of FnECHO modified treatment in 148 cases (42.50%) in the form of addition and/or change in the treatment or avoidance of unnecessary intervention. Conclusion FnECHO is frequently used in the NICU setting and may be a useful tool to guide treatment. PDA assessment and haemodynamic instability are the most frequent indications. To validate its usefulness, well co

  11. Performance of a Western blot assay to compare mother and newborn anti-Toxoplasma antibodies for the early neonatal diagnosis of congenital toxoplasmosis.

    PubMed

    Robert-Gangneux, F; Commerce, V; Tourte-Schaefer, C; Dupouy-Camet, J

    1999-09-01

    The aim of this study was to retrospectively evaluate the performance of a Western blot assay to compare mother and newborn anti-Toxoplasma gondii antibodies for the early neonatal diagnosis of congenital toxoplasmosis. Since specific anti-Toxoplasma IgM or IgA is detected inconstantly at birth in the neonate, the diagnosis of congenital toxoplasmosis is often delayed until 6-9 months, after IgG titers have been observed persistently. In this study, 81 paired samples from 60 mother/child pairs were tested for IgG and IgM patterns. All mothers had (or were strongly suspected to have) acquired toxoplasmosis during pregnancy. Specific IgM and IgA were simultaneously detected by immunocapture tests, and IgG was titrated. A serological and clinical follow-up of infants was conducted during the first year of life until the diagnosis of congenital toxoplasmosis could be either confirmed or ruled out. Seventeen of the 60 newborns were congenitally infected. Specific IgM or IgA was detected by immunocapture at birth in 76.5% and 70.6% of cord sera from infected neonates, respectively, with an equal specificity of 77.5%. Comparative Western blot allowed the detection of neosynthesized IgG and IgM in the cord blood of 50% and 78.6% of infected infants, respectively, with a specificity of 100%. The combination of IgA and IgM immunocapture tests, the analysis of IgG and IgM Western blot patterns, and the combination of both techniques allowed the detection of 94%, 94%, and 100% of cases within the first 3 months of life, respectively. In conclusion, Western blotting seems to be a useful complementary tool for the early postnatal diagnosis of congenital toxoplasmosis. PMID:10534187

  12. Overview of neonatal lupus.

    PubMed

    Johnson, Benay

    2014-01-01

    Neonatal lupus (NL) is defined by the presentation of the fetus and the newborn who possess autoantibodies received from the mother. It is the dysfunction of the maternal immune system that leads to the production of autoantibodies to anti-Sjögren syndrome-A, anti-Sjögren syndrome-B, and anti-ribonuclear protein antigens. These antibodies are shared through the placenta and produce bodily changes in the fetal skin and heart, as well as potential changes in other body systems. Congenital complete heart block is the most dangerous manifestation of NL that can occur in utero or after birth. This article will provide an overview the presentation of NL and current therapies. Prenatal steroids have been the mainstay of therapy to try to reverse first- and second-degree congenital heart block and to prevent progression to a more advanced stage. New therapies are combining steroids with intravenous immunoglobulin and plasmapheresis. This article will provide guidelines for practitioners so they can consider NL as a differential diagnosis when presented with cutaneous lesions, congenital heart block, or abnormal findings in the hematologic, hepatobiliary, neurologic, and musculoskeletal systems. PMID:24100008

  13. [Neonatal mucolipidosis type II].

    PubMed

    Hmami, F; Oulmaati, A; Bouharrou, A

    2016-01-01

    Mucolipidosis type II (ML II, OMIM 252,500) is an autosomal recessive disorder clinically characterized by facial dysmorphia similar to Hurler syndrome and pronounced gingival hypertrophy. The disorder is caused by a defect in targeting acid hydrolases on the surface of lysosomes, which impede their entry and lead to accumulation of undigested substrates in lysosomes. The onset of the symptoms is usually in infancy, beginning in the 6th month of life. Early onset, at birth or even in utero, is a sign of severity and involves the specific dysmorphia as well as skeletal dysplasia related to hyperparathyroidism. We report on a severe neonatal form of this disorder revealed by respiratory distress with severe chest deformity. The dysmorphic syndrome, combining coarse features, pronounced gingival hypertrophy, with diffuse bone demineralization and secondary hyperparathyroidism associating significant elevation of parathyroid hormone and alkaline phosphatase with normal levels of vitamin D and calcium were characteristics of mucolipidosis type II. Recognizing this specific association of anomalies helps eliminate the differential diagnosis and establish appropriate diagnosis and care. PMID:26552632

  14. Hypercatabolism of IgG in mice with lupus-like syndrome.

    PubMed

    Zhou, J; Pop, L M; Ghetie, V

    2005-01-01

    The metabolism of radioiodinated mouse IgG was studied in mice with lupus-like syndrome before and after the onset of the disease. Before the onset of the disease, the pharmacokinetic parameters of IgG in MLR-1pr and Pristane-primed Balb/c mice were within the normal range of values. After the onset of the disease a considerable increase in the catabolic rate of IgG was recorded abbreviating its half life to less than one third of the normal value. The increased catabolism of IgG could not be related to the concentration--catabolism effect or to the presence of rheumatoid factor and autoantibody or to the IgG loss through the kidney and gastrointestinal tract. The hypercatabolism of IgG was explained by disease-induced impairment of the function of the receptor FcRn, which regulates the homeostasis of IgG. PMID:16038110

  15. Orbital Pseudotumor: Uncommon Initial Presentation of IgG4-Related Disease

    PubMed Central

    Carbone, Teresa; Azêdo Montes, Ricardo; Andrade, Beatriz; Lanzieri, Pedro; Mocarzel, Luis

    2015-01-01

    IgG4-related disease (IgG4-RD) encompasses a group of fibroinflammatory conditions recognized in recent times. The main clinical features include variable degrees of tissue fibrosis, tumorlike expansions, perivascular lymphocytic infiltration rich in IgG4-positive plasma cells, and elevated serum IgG4. A case has been reported of an elderly patient with an unexplained unilateral exophthalmia; biopsy was performed and revealed lymphocytic infiltration, suggesting IgG4-RD. High serum levels of IgG4, in association with a good response to steroid therapy and to the exclusion of other diagnoses, confirmed the hypothesis of orbital pseudotumor by IgG4-RD. PMID:25838962

  16. Neisseria meningitidis Group A IgG1 and IgG2 Subclass Immune Response in African Children Aged 12–23 Months Following Meningococcal Vaccination

    PubMed Central

    Holme, Daniel; Findlow, Helen; Sow, Samba O.; Idoko, Olubukola T.; Preziosi, Marie-Pierre; Carlone, George; Plikaytis, Brian D.; Borrow, Ray

    2015-01-01

    Background. A group A meningococcal conjugate vaccine, PsA-TT, was licensed in 2010 and was previously studied in a phase 2 clinical trial to evaluate its safety and immunogenicity in African children 12–23 months of age. Methods. Subjects received either PsA-TT; meningococcal group A, C, W, Y polysaccharide vaccine (PsACWY); or Haemophilus influenzae type b conjugate vaccine (Hib-TT). Forty weeks following primary vaccination, the 3 groups were further randomized to receive either PsA-TT, one-fifth dose of PsACWY, or Hib-TT. Group A–specific immunoglobulin G (IgG) subclass response was characterized using an enzyme-linked immunosorbent assay. Results. The predominant IgG subclass response, regardless of vaccine, was IgG1. One month following primary vaccination, the geometric mean concentrations (GMCs) of IgG1 and IgG2 in the PsA-TT group were 21.73 µg/mL and 6.27 µg/mL, whereas in the PsACWY group the mean GMCs were 2.01 µg/mL and 0.97 µg/mL, respectively (P < .0001). Group A–specific IgG1 and IgG2 GMCs remained greater in the PsA-TT group than in the PsACWY group 40 weeks following primary vaccination (P < .0001). One week following revaccination, those given 2 doses of PsA-TT had the greatest IgG1 and IgG2 GMCs of 125.23 µg/mL and 36.12 µg/mL, respectively (P = .0008), and demonstrated a significant increase in IgG1:IgG2 mean ratio, indicative of the T-cell–dependent response associated with conjugate vaccines. Conclusions. Vaccination of African children aged 12–24 months with either PsA-TT or PsACWY elicited a predominantly IgG1 response. The IgG1:IgG2 mean ratio decreased following successive vaccination with PsACWY, indicating a shift toward IgG2, suggestive of the T-cell–independent immune response commonly associated with polysaccharide antigens. Clinical Trials Registration. SRCTN78147026. PMID:26553689

  17. Extensive Metastatic Cholangiocarcinoma Associated With IgG4-Related Sclerosing Cholangitis Misdiagnosed as Isolated IgG4-Related Sclerosing Cholangitis

    PubMed Central

    Zhang, Yi-An; Shen, Xi-Zhong; Zhu, Ji-Min; Liu, Tao-Tao

    2015-01-01

    Abstract As cholangiographic features of IgG4-related sclerosing cholangitis (IgG4-SC) resemble those of cholangiocarcinoma, it is highly confusing between the 2 conditions on the basis of cholangiographic findings. This study presents a case of extensive metastatic cholangiocarcinoma with IgG4-SC misdiagnosed as isolated IgG4-SC, and reviews recent studies of the 2 diseases. A 56-year-old man with no family history of malignant tumors or liver diseases presented with recurrent mild abdominal pain and distention for 3 months. Magnetic resonance cholangiopancreatography showed a 3.7 cm nodular lesion with unclear boundary in segment VI of the liver. Serum IgG4 and CA19-9 were slightly elevated. Histopathological examination was consistent with the consensus statement on the pathology of IgG4-SC. IgG4-SC was thus considered. Due to his mild symptoms, glucocorticoid was not given at first. However, 3 months after his first admission, he had more severe abdominal pain and further elevated serum CA19-9. Actually he was found suffering from extensive metastatic cholangiocarcinoma with IgG4-SC by exploratory laparotomy. The present case serves as a reminder that extensive metastatic cholangiocarcinoma with or without IgG4-SC may be misdiagnosed as an isolated IgG4-SC case if one relies solely on elevated serum and tissue IgG4 levels. We emphasize on the importance of repeated core needle biopsy or exploratory laparoscopy/laparotomy before immunosuppressive drugs are given, and on follow-up of imaging findings and serum CA19-9 once immunosuppressive therapy is started. PMID:26559312

  18. IgG Suppresses Antibody Responses in Mice Lacking C1q, C3, Complement Receptors 1 and 2, or IgG Fc-Receptors

    PubMed Central

    Bergström, Joakim J. E.; Heyman, Birgitta

    2015-01-01

    Antigen-specific IgG antibodies, passively administered to mice or humans together with large particulate antigens like erythrocytes, can completely suppress the antibody response against the antigen. This is used clinically in Rhesus prophylaxis, where administration of IgG anti-RhD prevents RhD-negative women from becoming immunized against RhD-positive fetal erythrocytes aquired transplacentally. The mechanisms by which IgG suppresses antibody responses are poorly understood. We have here addressed whether complement or Fc-receptors for IgG (FcγRs) are required for IgG-mediated suppression. IgG, specific for sheep red blood cells (SRBC), was administered to mice together with SRBC and the antibody responses analyzed. IgG was able to suppress early IgM- as well as longterm IgG-responses in wildtype mice equally well as in mice lacking FcγRIIB (FcγRIIB knockout mice) or FcγRI, III, and IV (FcRγ knockout mice). Moreover, IgG was able to suppress early IgM responses equally well in mice lacking C1q (C1qA knockout mice), C3 (C3 knockout mice), or complement receptors 1 and 2 (Cr2 knockout mice) as in wildtype mice. Owing to the previously described severely impaired IgG responses in the complement deficient mice, it was difficult to assess whether passively administered IgG further decreased their IgG response. In conclusion, Fc-receptor binding or complement-activation by IgG does not seem to be required for its ability to suppress antibody responses to xenogeneic erythrocytes. PMID:26619292

  19. Neonatal Screening Part 2: Neonatal Screening in Canada

    PubMed Central

    Morris, Brian A.P.

    1990-01-01

    Neonatal screening is a widely accepted, cost-effective method for early detection of various inborn errors of metabolism. This series of three articles examines different aspects of neonatal screening. In the first article, the author discussed general principles of screening and its function in the spectrum of diagnostic techniques for genetic disease. In this, the second article, the author reviews the history and current practices of neonatal screening in Canada. The individual diseases for which screening is used and particular points of interest for each of these diseases are briefly described. The author also outlines the benefits of screening and treatment. In the final article of this series, the author will examine controversial topics that represent the possible future of screening. PMID:21234041

  20. The Effects of Increased Maternal Visual Regard of Neonate Upon the Neonate-Mother Interaction.

    ERIC Educational Resources Information Center

    Belcastro, Christina M.; And Others

    This study attempts to investigate the effects of increased maternal visual regard on neonatal social visual behavior and upon patterns of mother-neonate interaction within the context of a learning theory paradigm. Subjects were 3-day-old neonates and their mothers; with 10 of the 15 mother-neonate pairs as the experimental group, and 5 as the…

  1. Neonatal hemochromatosis in monochorionic twins.

    PubMed

    Korkmaz, L; Baştuğ, O; Daar, G; Doğanay, S; Deniz, K; Kurtoğlu, S

    2015-01-01

    Neonatal hemochromatosis (NH) is a form of neonatal liver failure caused by maternal-fetal alloimmune injury to hepatocytes. The etiology of neonatal hemochromatosis is not exactly understood. However, according to one theory neonatal hemochromatosis is believed to be an alloimmune disorder causing liver injury in the fetus. In order to diagnose neonatal hemochromatosis there are some criteria that should be taken into account, such as positive family history, high serum ferritin levels, high serum alpha-fetoprotein levels and siderosis demonstrated by histology or with magnetic resonance.We present a case of a monochorionic newborn twin who applied to our hospital with sepsis clinical symptoms like clinics, was diagnosed with NH and immediately treated with antioxidant therapy while the other twin with same clinical symptoms did not respond to therapy and passed away. NH should be considered in the differential diagnosis of cases with sepsis-like clinical symptoms that do not respond to antibiotics; early antioxidant therapy in these cases is lifesaving. PMID:26836824

  2. Neonatal meningoencephalitis caused by Bacillus cereus.

    PubMed

    Manickam, Nisha; Knorr, Aimee; Muldrew, Kenneth L

    2008-09-01

    The classic organisms associated with central nervous system infection in the neonate are herpes simplex, Listeria monocytogenes, Escherichia coli, and Streptococcus agalactiae; we describe an unusual case of neonatal meningoencephalitis caused by Bacillus cereus. PMID:18679155

  3. Multicentric Castleman Disease With Tubulointerstitial Nephritis Mimicking IgG4-related Disease: Two Case Reports.

    PubMed

    Zoshima, Takeshi; Yamada, Kazunori; Hara, Satoshi; Mizushima, Ichiro; Yamagishi, Masakazu; Harada, Kenichi; Sato, Yasuharu; Kawano, Mitsuhiro

    2016-04-01

    Multicentric Castleman disease is a benign lymphoproliferative disorder with heterogenous clinical symptoms and involves systemic organs in addition to lymph nodes. Elevated serum IgG4 levels and IgG4-positive plasma cell (IgG4+PC) infiltrates have been reported in lymph nodes, lung and skin in some multicentric Castleman disease cases, resembling IgG4-related disease (IgG4-RD) histologically. However, no report has been available regarding IgG4+PC infiltration in the kidneys of multicentric Castleman disease. Here, we report 2 cases of multicentric Castleman disease complicated by IgG4-related disease (IgG4-RD) histologically. However, there has been no report published on PC-rich tubulointerstitial nephritis, lymphadenopathy, with numerous IgG4+PC infiltration, and elevated serum IgG4 levels, mimicking IgG4-RD. The blood examinations revealed systemic inflammation and elevated C-reactive protein and interleukin-6 levels. Corticosteroid therapy was partially effective in both cases, and combination therapy of corticosteroid and tocilizumab was needed in both cases. Moreover, after triple therapy with corticosteroid, rituximab and cyclophosphamide were used in 1 case to tame the severe inflammation. The present cases suggest that if continuously elevated serum C-reactive protein levels and partial corticosteroid responsiveness are encountered, multicentric Castleman disease should be considered rather than IgG4-RD as a differential diagnosis even if serum IgG4 is elevated and IgG4+PCs infiltrate systemic organs. PMID:26598921

  4. Covariance structures of fat and protein influence the estimation of IgG in bovine colostrum.

    PubMed

    Løkke, Mette Marie; Engelbrecht, Rikke; Wiking, Lars

    2016-02-01

    On-farm instruments for assessing colostrum quality are needed in order to ensure that the calf is supplied with enough IgG to avoid failure of passive transfer. The aim of this study was to evaluate methods for estimating the IgG concentration in cows' colostrum. This research included 126 colostrum samples from 21 Danish farms with different breeds, ensuring a broad variation pattern in IgG, total protein and fat concentration. Approximately one third of the samples did not fulfil the recommendation of >50 g IgG/l colostrum, and the IgG concentration decreased with time from calving to milking. The ratio of IgG to total protein varied from 6 to 61%, however IgG and total protein were correlated with r2 = 0.70. The variation in fat was independent of variations in protein and IgG. The IgG concentration was measured by ELISA and compared to fast measurements by specific gravity by colostrometer, Brix by refractometer and prediction from infrared spectroscopy. The three fast methods were all correlated to the total protein concentration of colostrum; however specific gravity was also influenced by the fat concentration. Furthermore, specific gravity generally overestimated the IgG concentration, and the cut-off level should be raised to 1050 in order to ensure adequate IgG in colostrum. None of the methods estimated IgG concentration better than the correlation of total protein and IgG, meaning that they all depended on the indirect correlation between total protein and IgG. The results suggest that using a refractometer for quality control of colostrum is an easy and feasible method, and a cut-off level of Brix 22 seems sufficient to assure adequate IgG concentration in colostrum fed to the calf. PMID:26869112

  5. IgG subclass responses to proinflammatory fraction of Brugia malayi in human filariasis

    PubMed Central

    Joseph, S.K.; Verma, S.K.; Sahoo, M.K.; Sharma, A.; Srivastava, M.; Reddy, M.V.R.; Murthy, P.K.

    2012-01-01

    Background & objectives: Earlier we demonstrated that immunization with F6, a proinflammatory molecular fraction isolated from the human filarial parasite Brugia malayi, protected the host and eliminated the infection in Mastomys coucha by a Th1/Th2 response including IgG2a antibody response. Whether F6 molecules become accessible to human host during natural course of infection and elicit similar response is not known. The present study was undertaken to determine the profile of IgG subclasses specifically reactive to F6 in different categories of bancroftian filariasis cases to infer any relationship between the levels of a particular F6-specific IgG subclass and the infection or disease status. Methods: Serum samples of normal individuals from filariasis non-endemic regions of India like Jammu & Kashmir, Uttarakhand, and Chandigarh [(NEN-W; n=10), healthy subjects from USA (NEN-U; n=10) and three categories of bancroftian filariasis cases from endemic areas: endemic normals (EN; n=10) with no symptoms and no microfilariae, asymptomatic microfilaremics (ASM; n=10) and chronic symptomatic amicrofilaremics (CL; n=10) were assayed for F6-specific IgG1, IgG2, IgG3 and IgG4 by ELISA using SDS-PAGE-isolated F6 fraction of B. malayi adult worms. Results: Significantly high levels of F6-specific IgG1, IgG2 and IgG3 were found in CL (P<0.001) and EN (P<0.01-0.001) bancroftian filariasis cases compared to NEN-U. Significant levels of F6-specific IgG1 (P<0.01) and IgG2 (P<0.01) but not IgG3 were found in ASM cases compared to NEN-U. The most abundant was IgG2 which when compared to NEN-U, was significantly high in CL (P<0.001) and EN cases (P<0.001), followed by ASM (P<0.01). F6-specific IgG4 response in EN, ASM and CL subjects was not significantly different from the levels of NEN-U. Among the non-endemic normals, the NEN-W subjects showed significant reactivity with IgG2 (P<0.001) but not with IgG1, IgG3 and IgG4 as compared to NEN-U subjects. IgG subclass levels were

  6. Clinical and laboratory characteristics of neonatal hypocalcemia

    PubMed Central

    Cho, Won Im; Yu, Hyeoh Won; Shin, Choong Ho; Yang, Sei Won; Choi, Chang Won; Kim, Beyong Il

    2015-01-01

    Purpose To describe the clinical characteristics of full-term neonates with hypocalcemia and to suggest factors associated with neonatal hypocalcemia Methods The medical records of full-term neonates with hypocalcemia were reviewed. Hypocalcemia was defined as an ionized calcium (iCa) concentration of <4 mg/dL. Parathyroid hormone (PTH) insufficiency was defined as a serum PTH level of <60 pg/mL or a serum phosphorus level higher than the serum calcium level in the presence of hypocalcemia. Results Fifty-three neonates were enrolled. The median age at diagnosis of hypocalcemia was 3 days. In all the neonates, formula feeding predominance was observed. Thirty-eight neonates (69.8%) were compatible with PTH insufficiency. The number of formula-fed neonates was significantly higher than that of breast-fed patients among neonates with PTH insufficiency (P=0.017). Intact PTH was negatively correlated with serum phosphorus levels. Twelve out of 14 neonates (85.7%) had 25-hydroxy vitamin D (25OHD) levels <20 ng/mL and 9 neonates (64.3%) had 25OHD levels <10 ng/mL. Twenty-one neonates had hypocalcemic tetany. The serum calcium and iCa concentrations of neonates with tetany were 4.2-8.3 mg/dL and 1.85-3.88 mg/dL, respectively. Three neonates showed symptomatic hypocalcemia with calcium levels over 7.5 mg/dL. Among the 16 neonates who underwent electroencephalography (EEG), 12 had abnormalities, which normalized after 1-2 months. Conclusion Formula milk feeding, PTH insufficiency and low serum vitamin D concentration are associated with the development of neonatal hypocalcemia. Symptoms such as tetany and QT interval prolongation can develop in relatively mild hypocalcemia. Moreover, transient neonatal hypocalcemia can cause transient EEG abnormalities. PMID:26191512

  7. Biliary atresia and neonatal hepatobiliary scintigraphy

    SciTech Connect

    Wynchank, S.; Guillet, J.; Leccia, F.; Soubiran, G.; Blanquet, P.

    1984-03-01

    Hepatobiliary scintigraphy using Tc-99m diethyl IDA was performed on 14 jaundiced neonates. It aided greatly the differential diagnosis between neonatal hepatitis and biliary atresia. Limitations in the interpretation of the results are described, as neonatal hepatitis may be accompanied by biliary excretion ranging from zero to normal. Also both biliary atresia (intra- and extrahepatic) and neonatal hepatitis may show no biliary excretion within 24 hours.

  8. Neonatal Jaundice Detection System.

    PubMed

    Aydın, Mustafa; Hardalaç, Fırat; Ural, Berkan; Karap, Serhat

    2016-07-01

    Neonatal jaundice is a common condition that occurs in newborn infants in the first week of life. Today, techniques used for detection are required blood samples and other clinical testing with special equipment. The aim of this study is creating a non-invasive system to control and to detect the jaundice periodically and helping doctors for early diagnosis. In this work, first, a patient group which is consisted from jaundiced babies and a control group which is consisted from healthy babies are prepared, then between 24 and 48 h after birth, 40 jaundiced and 40 healthy newborns are chosen. Second, advanced image processing techniques are used on the images which are taken with a standard smartphone and the color calibration card. Segmentation, pixel similarity and white balancing methods are used as image processing techniques and RGB values and pixels' important information are obtained exactly. Third, during feature extraction stage, with using colormap transformations and feature calculation, comparisons are done in RGB plane between color change values and the 8-color calibration card which is specially designed. Finally, in the bilirubin level estimation stage, kNN and SVR machine learning regressions are used on the dataset which are obtained from feature extraction. At the end of the process, when the control group is based on for comparisons, jaundice is succesfully detected for 40 jaundiced infants and the success rate is 85 %. Obtained bilirubin estimation results are consisted with bilirubin results which are obtained from the standard blood test and the compliance rate is 85 %. PMID:27229489

  9. Cardiogenic shock in a neonate

    PubMed Central

    Viveiros, Eulália; Aveiro, Ana Cristina; Costa, Edite; Nunes, José Luis

    2013-01-01

    We describe a case of a healthy male full-term neonate, 21 days old, admitted to the emergency room, presenting a severe cardiovascular collapse with an initial sinus rhythm. The first diagnostic hypothesis was of septic shock, having antibiotics, fluid resuscitation, inotropic drugs and ventilatory support started immediately. After achieving haemodynamic stability, a new cardiovascular collapse occurred with supraventricular tachycardia (SVT). The latter was successfully treated and the neonate did not suffer any organ damage. Cardiogenic shock should be considered despite being a much rarer cause of shock in neonates. SVT is promptly diagnosed when a cardiorespiratory monitor is available; however, the intermittent occurrence of the tachycardia episodes makes this diagnosis more difficult to recognise and manage. PMID:23737567

  10. 21 CFR 880.5400 - Neonatal incubator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Neonatal incubator. 880.5400 Section 880.5400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL... § 880.5400 Neonatal incubator. (a) Identification. A neonatal incubator is a device consisting of...

  11. 21 CFR 880.5400 - Neonatal incubator.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Neonatal incubator. 880.5400 Section 880.5400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL... § 880.5400 Neonatal incubator. (a) Identification. A neonatal incubator is a device consisting of...

  12. 21 CFR 880.5400 - Neonatal incubator.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Neonatal incubator. 880.5400 Section 880.5400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL... § 880.5400 Neonatal incubator. (a) Identification. A neonatal incubator is a device consisting of...

  13. 21 CFR 880.5400 - Neonatal incubator.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Neonatal incubator. 880.5400 Section 880.5400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL... § 880.5400 Neonatal incubator. (a) Identification. A neonatal incubator is a device consisting of...

  14. 21 CFR 880.5400 - Neonatal incubator.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Neonatal incubator. 880.5400 Section 880.5400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL... § 880.5400 Neonatal incubator. (a) Identification. A neonatal incubator is a device consisting of...

  15. Regulation of muscle growth in neonates

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This review reports recent findings on the multiple factors that regulate skeletal muscle growth in neonates. Skeletal muscle is the fastest growing protein mass in neonates. The high rate of neonatal muscle growth is due to accelerated rates of protein synthesis accompanied by the rapid accumulatio...

  16. Amino acids and insulin in neonatal growth

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The rate of growth during the neonatal period is greater than at any other stage of postnatal life, and a majority of the mass increase is skeletal muscle. The rapid growth of skeletal muscle in the neonate is driven by an elevated rate of protein synthesis. Neonates are very efficient at utilizin...

  17. Small-Angle X-ray Scattering Screening Complements Conventional Biophysical Analysis: Comparative Structural and Biophysical Analysis of Monoclonal Antibodies IgG1, IgG2, and IgG4

    PubMed Central

    Tian, Xinsheng; Langkilde, Annette E; Thorolfsson, Matthias; Rasmussen, Hanne B; Vestergaard, Bente

    2014-01-01

    A crucial step in the development of therapeutic monoclonal antibodies is the selection of robust pharmaceutical candidates and screening of efficacious protein formulations to increase the resistance toward physicochemical degradation and aggregation during processing and storage. Here, we introduce small-angle X-ray scattering (SAXS) to characterize antibody solution behavior, which strongly complements conventional biophysical analysis. First, we apply a variety of conventional biophysical techniques for the evaluation of structural, conformational, and colloidal stability and report a systematic comparison between designed humanized IgG1, IgG2, and IgG4 with identical variable regions. Then, the high information content of SAXS data enables sensitive detection of structural differences between three IgG subclasses at neutral pH and rapid formation of dimers of IgG2 and IgG4 at low pH. We reveal subclass-specific variation in intermolecular repulsion already at low and medium protein concentrations, which explains the observed improved stability of IgG1 with respect to aggregation. We show how excipients dramatically influence such repulsive effects, hence demonstrating the potential application of extensive SAXS screening in antibody selection, eventual engineering, and formulation development. PMID:24700358

  18. Bovine IgG2a antibodies to Haemophilus somnus and allotype expression.

    PubMed Central

    Corbeil, L B; Gogolewski, R P; Kacskovics, I; Nielsen, K H; Corbeil, R R; Morrill, J L; Greenwood, R; Butler, J E

    1997-01-01

    Bovine IgG2a has been implicated in protection against pyogenic infections, including those caused by Haemophilus somnus. To further investigate the role of IgG2a in defense against H. somnus, IgG1 and IgG2a antibodies were purified from antiserum against an immunodominant 40 kDa outer membrane protein (p40) of H. somnus, which was previously shown to passively protect calves against H. somnus pneumonia. The passive protective capacity of anti-p40 IgG1 or IgG2a was evaluated in vivo in calves. Purified anti-p40 IgG1 or IgG2a was incubated with H. somnus for 15 min before intrabronchial inoculation of calves. Bacteria incubated with anti-p40 IgG1 or IgG2a were inoculated into one caudal lung lobe and bacteria incubated with IgG1 or IgG2a from the respective preimmunization serum were inoculated into the contralateral lobe. The volumes of pneumonia in the right and left lungs were determined 24 h later. The difference in volume of pneumonia with H. somnus preincubated in IgG1 pre- and postimmunization anti p40 was less (16 cm3, P = 0.298) than the difference in volume of pneumonia with H. somnus preincubated in IgG2a pre- and postimmunization anti p40 (30 cm3, P = 0.146). Although the differences in lesion size between pre- and postimmunization serum were not statistically significant, the trend suggests IgG2a may be more protective than IgG1. To examine this further, the peptide specificity of these IgG1 and IgG2a antibodies to p40 was examined. After limited proteolysis of p40, IgG2a antibodies reacted with 2 peptides not recognized by IgG1 antibodies. Other peptides were recognized by both isotypes. Since these studies suggested that IgG2a may be important in protection against infection, we then investigated some aspects of the role of the 2 IgG2a allotypes, A1 and A2. In retrospective studies of age differences in expression of IgG2a allotypes, no heterozygotes were detected in calves of 60 d old or less, and fewer heterozygotes were detected in calves 61-120 d

  19. Neonatal records and the computer.

    PubMed Central

    Walker, C H

    1977-01-01

    To use a combined single document clinical case sheet/computer record which can form the basic document for a life medical record is a practical proposition. With adequate briefing doctors and nurses soon become familiar with the record and appreciate its value. Secretarial and clerical requirements are reduced to a minimum as transcription of medical data is eliminated, so greatly speeding up processing and feed back to the medical services. A few illustrations of trends in neonatal statistics and of computer linked maternal/neonatal data are presented. PMID:879830

  20. Interprofessional Education in Neonatal Care.

    PubMed

    Kenner, Carole

    2016-01-01

    Interprofessional education is not a new concept. Yet, the operationalization of interprofessional education with related competencies for collaborative team-based practice in neonatal units is often difficult. Changes in healthcare with an emphasis on patient-focused care and the concern for patient safety and quality care are accelerating the need for more interprofessional education. This article briefly outlines the evolution of interprofessional education to support collaborative team-based practice and how that facilitates safety and quality care in neonatal units. PMID:27465448

  1. IgG Conformer's Binding to Amyloidogenic Aggregates

    PubMed Central

    Phay, Monichan; Welzel, Alfred T.; Williams, Angela D.; McWilliams-Koeppen, Helen P.; Blinder, Veronika; O'Malley, Tiernan T.; Solomon, Alan; Walsh, Dominic M.; O'Nuallain, Brian

    2015-01-01

    Amyloid-reactive IgGs isolated from pooled blood of normal individuals (pAbs) have demonstrated clinical utility for amyloid diseases by in vivo targeting and clearing amyloidogenic proteins and peptides. We now report the following three novel findings on pAb conformer's binding to amyloidogenic aggregates: 1) pAb aggregates have greater activity than monomers (HMW species > dimers > monomers), 2) pAbs interactions with amyloidogenic aggregates at least partially involves unconventional (non-CDR) interactions of F(ab) regions, and 3) pAb's activity can be easily modulated by trace aggregates generated during sample processing. Specifically, we show that HMW aggregates and dimeric pAbs present in commercial preparations of pAbs, intravenous immunoglobulin (IVIg), had up to ~200- and ~7-fold stronger binding to aggregates of Aβ and transthyretin (TTR) than the monomeric antibody. Notably, HMW aggregates were primarily responsible for the enhanced anti-amyloid activities of Aβ- and Cibacron blue-isolated IVIg IgGs. Human pAb conformer's binding to amyloidogenic aggregates was retained in normal human sera, and mimicked by murine pAbs isolated from normal pooled plasmas. An unconventional (non-CDR) component to pAb's activity was indicated from control human mAbs, generated against non-amyloid targets, binding to aggregated Aβ and TTR. Similar to pAbs, HMW and dimeric mAb conformers bound stronger than their monomeric forms to amyloidogenic aggregates. However, mAbs had lower maximum binding signals, indicating that pAbs were required to saturate a diverse collection of binding sites. Taken together, our findings strongly support further investigations on the physiological function and clinical utility of the inherent anti-amyloid activities of monomeric but not aggregated IgGs. PMID:26367058

  2. Ophthalmic immunoglobulin G4-related disease IgG4-RD Current concepts.

    PubMed

    Mulay, Kaustubh; Wick, Mark R

    2016-05-01

    IgG4-related disease (IgG4-RD) is a distinct entity that frequently occurs in an ophthalmic location. As such, IgG4-RD is not limited to the orbit but may also involve other anatomical structures in and around the eye. Hence, the term 'ophthalmic IgG4-RD' is preferred over 'orbital IgG4-RD.' A high level of suspicion for the diagnosis can be derived from careful clinicoradiologic examination; the use of immunohistochemical staining for IgG4 in the context of characteristic histopathologic features is needed to reach a correct diagnosis. Recently described diagnostic criteria for ophthalmic IgG4-RD address subtle, yet significant, differences from IgG4-RD as seen in other systemic sites. Serum IgG4 titers are neither sensitive nor specific for the diagnosis of IgG4-RD and should not relied upon solely. Although most cases respond well to therapy with glucocorticoids, refractoriness to treatment and relapses are common. They necessitate the use of additional immunotherapy in such patients. PMID:26897039

  3. Severe IgG4-Related Disease in a Young Child: A Diagnosis Challenge

    PubMed Central

    Ferraz, Catarina; Nunes, Teresa; Fonseca, Elsa; Vaz, Luísa Guedes

    2015-01-01

    Immunoglobulin G4-related disease (IgG4-RD) is an increasingly recognized syndrome that can appear with multiple organ involvement, typically with tumor-like swelling, lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, and elevated serum IgG4 concentrations. We report the case of a 22-month-old female child with failure to thrive and recurrent respiratory tract infections since 8 months of age. Physical examination was normal except for pulmonary auscultation with bilateral crackles and wheezes. Laboratory tests revealed elevated erythrocyte sedimentation rate, and elevated serum IgG and IgG4 with polyclonal hypergammaglobulinemia. Thoracic CT and MRI showed multiple mediastinal lymphadenopathies and a nodular posterior mediastinal mass in right paratracheal location with bronchial compression. Initial fine needle aspiration biopsy was compatible with reactive lymphadenopathy but after clinical worsening a thoracoscopic partial resection of the mass was performed and tissue biopsy revealed lymphoplasmacytic infiltrate and increased number of IgG4-positive plasma cells and a ratio of IgG4/IgG positive cells above 40%. Glucocorticoids therapy was started with symptomatic improvement, reduction in the size of the mass, and decrease of serum IgG4 levels after 6 weeks. There are very few reports of IgG4-RD in children. Long-term follow-up is necessary to monitor relapses and additional organ involvement. PMID:25705537

  4. A case of adenoid cystic carcinoma associated with IgG4-related disease

    PubMed Central

    Shimo, Tsuyoshi; Yao, Mayumi; Takebe, Yuichiro; Ono, Yuko; Obata, Kyoichi; Kurio, Naito; Ibaragi, Soichiro; Yoshioka, Norie; Kishimoto, Koji; Yanagi, Yoshinobu; Nagatsuka, Hitoshi; Sasaki, Akira

    2015-01-01

    Introduction Immunoglobulin G4-related disease (IgG4-RD) is an inflammatory condition associated with elevated serum IgG4 levels and tissue infiltration by IgG4-expressing plasma cells. We present a case of adenoid cystic carcinoma (ACC) of the submandibular gland with possible involvement of IgG4-RD. Presentation of case The patient was a 59-year-old man presenting with a swollen right submandibular gland. Laboratory tests revealed IgG4 levels of 176 mg/dl (reference range: 4.8–105). An initial open biopsy for histological diagnosis showed chronic sialadenitis. The region was monitored on an outpatient basis, and finally the right submandibular was totally resected because malignant tumor could not be excluded. Histological examination of the submandibular gland showed an ACC with lymphocytic infiltration containing many IgG4-positive plasma cells in the tumor stroma. Discussion We have described a case that indicated a possible involvement of ACC with IgG4-RD. This allows us to speculate that longstanding IgG4-RD may progress to malignancy or infiltration of IgG4-positive plasma cells through the signals of tumor stimuli. Further investigations are required to determine the potential pathogenic mechanism underlying this unique tumor. Conclusion This case underscores that caution is needed in the diagnosis of masses with high serum IgG4 levels, as the differential diagnosis includes malignancy. PMID:25781921

  5. Effect of Anti-Epileptic Drugs on Serum Level of IgG Subclasses

    PubMed Central

    Ashrafi, Mahmoud-Reza; Hosseini, Seyed-Ahmad; Biglari, Mohammad; Abolmaali, Sarah; Azizi Malamiri, Reza; Mombeini, Hoda; Pourpak, Zahra; Saladjegheh, Narges; Rezaei, Nima; Samadian, Azam; Aghamohammadi, Asghar

    2010-01-01

    Objective There are some controversial studies on effects of anti-epileptic drugs (AEDs) on serum IgG subclasses; however, the role of these medications is still unclear. The aim of this study was evaluation the effects of anti-epileptic drugs on serum concentration of IgG and its subclasses Methods Serum IgG and IgG subclasses of 61 newly diagnosed epileptic patients were measured at the beginning of monotherapy with carbamazepine, sodium valproate, and phenobarbital, and 6 months later. Measurement of IgG and its subclasses was performed using nephlometry and ELISA techniques, respectively. Findings Reduction of at least one IgG subclass was found in 6 patients 6 months after treatment with AEDs. Among 27 patients receiving carbamazepine, decrease in at least one serum IgG subclass level was found in 5 patients. Among 20 patients using sodium valproate, only one patient showed decrease in IgG2 subclass. None of the 14 patients using phenobarbital revealed significant decrease in IgG subclasses. No infection was seen in the patients with reduction of subclasses. Conclusion Although in our study, children with selective IgG subclass deficiency were asymptomatic, assessment of serum immunoglobulin levels could be recommended at starting the administration of AEDs and in serial intervals afterward in epileptic patients. PMID:23056716

  6. Evaluation of IgG subclass responses against Dermatophagoides farinae allergens in healthy and atopic dogs.

    PubMed

    Hou, Chia-Chun; Day, Michael J; Nuttall, Timothy J; Hill, Peter B

    2006-04-01

    A semiquantitative chemiluminescent Western blot analysis system was developed and validated to evaluate antigen-specific IgG subclass responses to electrophoretically separated proteins of Dermatophagoides farinae in healthy and atopic dogs. Both groups mounted similar D. farinae-specific IgG1 and IgG4 responses to multiple antigens, but IgG2 and IgG3 responses were difficult to detect. The most commonly recognized bands in both groups were 18 and 98 kDa antigens for IgG1 and 18, 45, 66, 98, 130 and 180 kDa for IgG4. The number of bands recognized per dog did not differ significantly, but significantly more atopic dogs had an IgG1 response to a 180 kDa protein. The overall D. farinae-specific IgG1 and IgG4 responses were slightly higher, but not significantly different, in the healthy group. The results suggest that some antigens produced by D. farinae can induce different subclass responses. However, as most of these responses are seen in both healthy and atopic dogs, they are likely to merely represent recognition of foreign proteins presented to the immune system, rather than involvement in the pathogenesis of atopic dermatitis. The role of the 180 kDa antigen warrants further study. PMID:16515652

  7. Erdheim-Chester Disease as a Mimic of IgG4-Related Disease

    PubMed Central

    Gianfreda, Davide; Musetti, Claudio; Nicastro, Maria; Maritati, Federica; Cobelli, Rocco; Corradi, Domenico; Vaglio, Augusto

    2016-01-01

    Abstract Immunoglobulin-G4 (IgG4)-related disease (IgG4RD) is a fibro-inflammatory disorder characterized by tissue-infiltrating IgG4+ plasma cells, and, often, high serum IgG4. Several autoimmune, infectious, or proliferative conditions mimic IgG4RD. Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis, characterized by foamy histiocytic infiltration, fibrosis, and chronic inflammation. ECD and IgG4RD manifestations may overlap. A patient presented with huge fibrous retroperitoneal masses causing compression on neighboring structures; the case posed the challenge of the differential diagnosis between IgG4RD and ECD mainly because of a prominent serum and tissue IgG4 response. Retroperitoneal biopsy led to the diagnosis of ECD; the V600E BRAF mutation was found. Treatment with the BRAF inhibitor vemurafenib was started. Treatment failed to induce mass regression and the patient died after 3 months of therapy. Prompted by this case, we examined serum and tissue IgG4 in a series of 15 ECD patients evaluated at our center, and found that approximately one-fourth of the cases have increased IgG4 in the serum and often in the tissue. The differential diagnosis between IgG4RD and ECD can be challenging, as some ECD patients have prominent IgG4 responses. This suggests the possibility of common pathogenic mechanisms between ECD and IgG4RD. PMID:27227923

  8. Therapeutic approach to IgG4-related disease

    PubMed Central

    Brito-Zerón, Pilar; Kostov, Belchin; Bosch, Xavier; Acar-Denizli, Nihan; Ramos-Casals, Manuel; Stone, John H.

    2016-01-01

    Abstract To review the reported evidence on the therapeutic management of IgG4-related disease (IgG4-RD) in clinical practice. A systematic search of the literature was conducted. The primary outcome measured was the rate of efficacy of first-line therapeutic approaches. Secondary outcomes measured included the rate of disease relapse, the outcome of untreated patients, the rate of patients without drug therapy at the end of follow-up, the rate of side effects, and mortality. The MOOSE, AHRQ, STROBE, and GRACE recommendations/statements were followed. The results of the systematic search strategy yielded 62 studies that included a total of 3034 patients. Complete information about first-line therapeutic regimens was detailed in 1952 patients, including glucocorticoid-based regimens in 1437 (74%), drug-free regimens in 213 (11%), and other therapies in 38 (2%). No therapy (wait and see management) was reported in 264 (13%) patients. The efficacy of monotherapy with glucocorticoids was specified in 1220 patients, of whom 97% had a therapeutic response. Relapses, however, were reported in 464/1395 (33%) patients despite typically short follow-up periods. Therapeutic efficacy was reported in 219/231 (95%) of relapses treated with glucocorticoids, 56/69 (81%) of those treated with azathioprine, 16/22 (72%) of those treated with other immunosuppressive agents, and in the 9 cases treated with rituximab (100%). In 14 studies, the authors detailed the outcome of 159/246 patients with wait-and-see management; spontaneous improvement or resolution was reported in 68 (43%) cases. Wide heterogeneity was observed with respect to the first-line therapeutic approaches used for the different organ-specific disease subsets, including significant differences in the mean dose of glucocorticoids used. Nearly 70% of reported IgG4-RD patients are treated with oral glucocorticoids in monotherapy. However, the therapeutic management is heavily influenced by geographical, epidemiological

  9. Colostrum quality affects immune system establishment and intestinal development of neonatal calves.

    PubMed

    Yang, M; Zou, Y; Wu, Z H; Li, S L; Cao, Z J

    2015-10-01

    The first meal of a neonatal calf after birth is crucial for survival and health. The present experiment was performed to assess the effects of colostrum quality on IgG passive transfer, immune and antioxidant status, and intestinal morphology and histology in neonatal calves. Twenty-eight Holstein neonatal male calves were used in the current study, 24 of which were assigned to 1 of 3 treatment groups: those that received colostrum (GrC), transitional milk (GrT, which was obtained after the first milking on 2-3 d after calving), and bulk tank milk (GrB) only at birth. The 4 extra neonatal calves who were not fed any milk were assigned to the control group and were killed immediately after birth to be a negative control to small intestinal morphology and histology detection. Calves in GrC gained more body weight than in GrT, whereas GrB calves lost 0.4 kg compared with the birth weight. Serum total protein, IgG, and superoxide dismutase concentrations were highest in GrC, GrT was intermediate, whereas GrB was the lowest on d 2, 3, and 7. Apparent efficiency of absorption at 48 h, serum complement 3 (C3), and complement 4 (C4) on d 2, 3, and 7 in GrB was low compared with GrC and GrT. On the contrary, malondialdehyde on d 7 increased in GrB. Calves in GrC had better villus length and width, crypt depth, villus height/crypt depth (V/C) value, and mucosal thickness in the duodenum, jejunum, and ileum, whereas GrT calves had lower villus length and width, crypt depth, and mucosal thickness than those fed colostrum. Villi of calves in GrB were nonuniform, sparse, severely atrophied, and apically abscised, and Peyer's patches and hydroncus were detected. Overall, colostrum is the best source for calves in IgG absorption, antioxidant activities, and serum growth metabolites, and promoting intestinal development. The higher quality of colostrum calves ingested, the faster immune defense mechanism and the more healthy intestinal circumstances they established. PMID:26233454

  10. A novel immunopathological association of IgG4-RD and vasculitis with Hashimoto's thyroiditis

    PubMed Central

    Minamino, Hiroto; Ariyasu, Hiroyuki; Furuta, Hiroto; Nishi, Masahiro; Yoshimasu, Takashi; Nishikawa, Akinori; Nakanishi, Masanori; Tsuchihashi, Shigeki; Kojima, Fumiyoshi; Murata, Shin-ichi; Inoue, Gen; Akamizu, Takashi

    2016-01-01

    Summary A 73-year-old man with Hashimoto's thyroiditis (HT) suffered from purpura on the lower legs. He was diagnosed with IgG4-related disease (IgG4-RD) with serum IgG4 elevation and dacryo-sialadenitis confirmed histologically. Serum Th2 and Treg cytokines, interleukin 7 (IL7), IL8 and Th2 chemokine levels were elevated, while skewed Th1 balance was seen in fluorescence-activated cell sorting (FACS). Therefore, preferential Th1 balance in HT appeared to be followed by IgG4-RD characterized with Th2 and Treg polarization. The commencement of steroid therapy dramatically exacerbated clinical manifestations including IgG4-RD-associated HT. The measurement of cytokine and chemokine levels as well as FACS analysis in the development of IgG4-RD seemed to be beneficial. In conclusion, an innovative association of HT, IgG4-RD and vasculitis was observed. This report also offers novel diagnostic and therapeutic approaches for IgG4-RD. Learning points Recently, a subtype of HT has been considered to be a thyroid manifestation of IgG4-RD, although the etiology of IgG4-RD is not established yet. Immunologically a close association between HT and vasculitis was reported. Leukocytoclastic vasculitis is a rare skin presentation of IgG4-RD. In the current case, during the course of HT, IgG4-RD and leukocytoclastic vasculitis occurred; thus, innate immunity and acquired immunity seem to be involved in the development of IgG4-RD. The measurement of cytokine and chemokines appeared to be beneficial in the development of IgG4-RD. Remarkably, effectiveness of steroid therapy for HT suggested presence of IgG4-RD-associated HT. Therefore, this report highlights the pathogenesis of IgG4-RD and proposes novel therapeutic mechanisms. Clinicians should pay attention to the development of IgG4-RD and vasculitis during long course of HT. PMID:26966543

  11. Fetal and Neonatal Alloimmune Thrombocytopenia

    PubMed Central

    CONSTANTINESCU, Simona; ZAMFIRESCU, Vlad; VLADAREANU, Prof. Radu

    2012-01-01

    ABSTRACT Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is the commonest cause of severe neonatal thrombocytopenia. FNAIT is usually suspected in neonates with bleeding or severe, unexplained, and/or isolated postnatal thrombocytopenia. Affected fetuses should be managed in referral centers with experience in the ante-natal management of FNAIT. Close collaboration is required between specialists in fetal medicine, obstetrics, hematology/transfusion medicine, and pediatrics. The mother and her partner should be provided with detailed information about FNAIT and its potential clinical consequences, and the benefits and risks of different approaches to ante-natal management. There has been huge progress in the ante-natal management of FNAIT over the last 20 years. However, the ideal effective treatment without significant side effects to the mother or fetus has yet to be determined. Key issues: Fetal and neonatal alloimmune thrombocytopenia is a condition that is underdiagnosed. Immunization seldom occurs in the first pregnancy. Immunization takes place in association with delivery in most cases. Anti-HPA-1a level is a predictor for the severity of thrombocytopenia. PMID:23482913

  12. Microbiome Development in Neonatal Calves

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The initial colonization of eukaryotic hosts by microbial populations is poorly understood, yet this remains a critical time for growth and development. The goals of this study were to characterize the microbiome of neonatal calves. Terminal restriction fragment length polymorphism (T-RFLP) analysis...

  13. Eruption cysts in the neonate.

    PubMed

    Ricci, Hérica Adad; Parisotto, Thaís Manzano; Giro, Elisa Maria Aparecida; de Souza Costa, Carlos Alberto; Hebling, Josimeri

    2008-01-01

    Disturbances of the dental development may result in anomalies, which may be apparent as soon as the child is born. Eruption cysts are rarely observed in neonates considering that at this stage of the child's life teeth eruption is uncommon. Thus, the aim of this report is to describe a case of eruption cysts in a neonate. A male neonate was brought to the emergency service with the chief complaint of an elevated area on the anterior region of the inferior alveolar ridge. The lesion was clinically characterized as a compressive and floating swelling. Through a radiographic exam two mandibular primary incisors could be seen superficially located. Due to the patient's age and the initial diagnosis of eruption cysts the conduct adopted was clinical surveillance. Forty-five days after the first visit the lesions had significantly decreased in size, and completely disappeared after 4 months. At that age, both mandibular central incisors were already in the oral cavity exhibiting small hypoplastic areas in the incisal edges. The clinical and radiographic follow-up of eruption cysts in neonates appears to be an adequate conduct without differing from that recommended for older children. PMID:18524277

  14. [Top five neonatal articles 2015].

    PubMed

    Flamant, C; Fischer Fumeaux, C J

    2016-09-01

    This review includes five randomized controlled trials, published in the Medline database in 2015, which were selected by the Scientific commission of the French society of neonatology, taking into account their influence in perinatology. This selection was presented during the specific "Top five" session in the French congress of neonatal research. PMID:27431853

  15. Arginine production in the neonate

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Endogenous arginine synthesis in adults is a complex multiorgan process, in which citrulline is synthesized in the gut, enters the general circulation, and is converted into arginine in the kidney, by what is known as the intestinal-renal axis. In neonates, the enzymes required to convert citrulline...

  16. Photodegradation of riboflavin in neonates

    SciTech Connect

    Sisson, T.R.

    1987-04-01

    The biologically most important flavins are riboflavin and its related nucleotides, all highly sensitive to light. It is because of its photoreactivity and its presence in almost all body fluids and tissues that riboflavin assumes importance in phototherapy of neonatal jaundice. The absorption maxima of both bilirubin and riboflavin in the body are nearly identical: 445-450 (447) nm. In consequence, blue visible light will cause photoisomerization of bilirubin accompanied by photodegradation of riboflavin. This results in diminished erythrocyte glutathione reductase, which indicates generalized tissue riboflavin deficiency and red cell lysis. Single- and double-strand breaks in intracellular DNA have occurred with phototherapy. This light exposure of neonates may result also in alterations of bilirubin-albumin binding in the presence of both riboflavin and theophylline (the latter frequently given to prevent neonatal apnea). Many newborns, especially if premature, have low stores of riboflavin at birth. The absorptive capacity of premature infants for enteral riboflavin is likewise reduced. Consequently, inherently low stores and low intake of riboflavin plus phototherapy for neonatal jaundice will cause a deficiency of riboflavin at a critical period for the newborn. Supplementation to those infants most likely to develop riboflavin deficiency is useful, but dosage, time, and mode of administration to infants undergoing phototherapy must be carefully adjusted to avoid unwanted side effects.

  17. Determination of IgG and IgM levels in sera of newborn calves until the 10th day of life by ELISA and description of their correlation to total plasma protein concentration and GGT activity.

    PubMed

    Bender, Petra; Bostedt, Hartwig

    2009-02-01

    The aim of this study was the determination of IgG and IgM concentrations in sera of 15 vital and healthy calves from the day of birth to the 10th day of life using two ELISAs exclusively developed for this purpose. We investigated if and to which extent the sera profiles were correlated with antibody levels in the colostral milk administered, with GGT activity and with total plasma protein content. Due to the assays' high sensitivity, traces of IgG and IgM in calf sera could be determined prior to the first uptake of the foremilk. Throughout the colostrum administration period until the 12th living hour, IgG and IgM levels remarkably increased (P < 0.0001).The correlation between IgG concentrations in sera determined 24 h post natum and the IgG content of the colostrum administered was highly significant (P < 0.001; r = 0.851), while the correlation of seral IgM levels 24 h post natum and the IgM content of the foremilk was significant (P = 0.009; r = 0.651). The sum of the IgG and IgM concentrations in calf serum 24 h post natum was significantly correlated with the neonatal plasma protein level (P = 0.01; r = 0.642). With P = 0.012; r = 0.629 and P = 0.029; r = 0.561 respectively, there was also a significant correlation between the subjects' IgG and IgM concentrations at 24 h post natum and the GGT activity in calf serum. By looking at individual cases, it became evident that the administration of colostrum containing maximum or minimum immunoglobulin concentrations does not necessarily result in the respective sera immunoglobulin concentrations. From these findings, as well as from the fact that numerous subjects displayed their highest IgG and IgM sera concentrations well after the gut closure, we conclude that individually diverse resorption patterns are in place which cannot be characterized by immunoglobulin measurements only. The determination of the total plasma protein content or GGT activity in calf serum at 24 h post natum only give a rough idea about

  18. 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. PMID:26660641

  19. An autoanalyzer test for the quantitation of platelet-associated IgG

    NASA Technical Reports Server (NTRS)

    Levitan, Nathan; Teno, Richard A.; Szymanski, Irma O.

    1986-01-01

    A new quantitative antiglobulin consumption (QAC) test for the measurement of platelet-associated IgG is described. In this test washed platelets are incubated with anti-IgG at a final dilution of 1:2 million. The unneutralized fraction of anti-IgG remaining in solution is then measured with an Autoanalyzer and soluble IgG is used for calibration. The dose-response curves depicting the percent neutralization of anti-IgG by platelets and by soluble IgG were compared in detail and found to be nearly identical, indicating that platelet-associated IgG can be accurately quantitated by this method. The mean IgG values were 2287 molecules/platelet for normal adults and 38,112 molecules/platelet for ITP patients. The Autoanalyzer QAC test is a sensitive and reproducible assay for the quantitation of platelet-associated IgG.

  20. A RECOMBINANT IgG Fc THAT RECAPITULATES THE ANTI-INFLAMMATORY ACTIVITY OF IVIG

    PubMed Central

    Anthony, Robert M.; Nimmerjahn, Falk; Ashline, David J.; Reinhold, Vernon N.; Paulson, James C.; Ravetch, Jeffrey V.

    2008-01-01

    High doses of monomeric IgG purified from pooled human plasma confer anti-inflammatory activity for a wide variety of autoimmune diseases. The heterogeneity of IVIG, derived from its Fab specificity, IgG subclass distribution and variable glycosylation have confounded efforts to develop a recombinant substitute for this blood-derived product. Recent studies have demonstrated that this paradoxical anti-inflammatory activity of IgG is completely dependent on sialylation of the N-linked glycan of the IgG Fc fragment. Determining the precise glycan requirements for this anti-inflammatory activity allowed appropriate glycan engineering of an IgG1 Fc fragment, leading to the generation of a fully recombinant, sialylated IgG1 Fc with greatly enhanced potency. PMID:18420934

  1. Autoimmune antibody (IgG Kansas) against the fibrin stabilizing factor (factor XIII) system.

    PubMed Central

    Lorand, L; Velasco, P T; Rinne, J R; Amare, M; Miller, L K; Zucker, M L

    1988-01-01

    Serum from a patient who died from massive hemorrhage within 4 months after onset of an acquired bleeding disorder at age 85 contained a potent inhibitor of fibrin stabilization. Other parameters of coagulation and fibrinolysis and his bleeding time were within normal limits. The inhibitor was shown to be an IgG with kappa light chains (IgG Kansas); its specific target was the factor XIII system itself. Although IgG Kansas combined with the virgin [ab] form of the zymogen, it did not block the thrombin-catalyzed conversion to [a'b]. However, IgG Kansas prevented the subsequent Ca2+-mediated activation of [a'b] to a + b, where a denotes the catalytically competent factor XIIIa species. IgG Kansas, in contrast to a previously studied autoimmune antibody from a similar bleeding disorder (IgG Warsaw), could also inhibit the transamidating activity of the preactivated a enzyme. Images PMID:3422419

  2. The sequential appearance of IgG subclasses and IgE during the course of Trichinella spiralis infection.

    PubMed Central

    Ljungström, I; Hammarström, L; Kociecka, W; Smith, C I

    1988-01-01

    Earlier studies have shown that IgG1 and IgG4 are the dominant IgG subclasses in the specific response during a chronic helminthic infection. It has also been suggested that IgG4 production results from chronic or repetitive antigenic stimulation and a correlation between IgG4 and IgE levels exists. An outbreak of Trichinella spiralis infection in Poland provided the opportunity to follow the sequential appearance of the IgG subclass and IgE responses in 15 patients during the early stage of Trichinella infection and to compare these observations in sera obtained one year later from the same patients. The results show that the sequential appearance of the IgG subclasses were IgG1 before IgG3 and IgG3 before IgG4. IgG1 antibodies dominated the immune response in all patients. A statistically significant increase in the number of IgG4 positive sera was observed in patients during the chronic stage compared to the findings during the early stage of infection (13% vs 73%; p less than 0.001), supporting the view that IgG4 results from a chronic antigenic stimulation. A correlation between the appearance of IgG4 and IgE was not found. The highest levels of IgE were seen in the first serum samples obtained, with a decrease during the course of infection. PMID:3224442

  3. In men at risk of HIV infection, IgM, IgG1, IgG3, and IgA reach the human foreskin epidermis.

    PubMed

    Lemos, M P; Karuna, S T; Mize, G J; Fong, Y; Montano, S M; Ganoza, C; Lama, J R; Sanchez, J; McElrath, M J

    2016-05-01

    We profiled the humoral response in the penis, an area that has been minimally explored but may be relevant for protecting insertive men against HIV and other sexually acquired infections. Comparing paired tissue samples from 20 men at risk of HIV infection, foreskin contains less immunoglobulin A (IgA) and more IgG2 than colon. Using foreskin dermal and epidermal explants and paired plasma from 17 men, we examined Ig accumulation by normalizing Ig to human serum albumin (HSA) transudation. Dermal IgM, IgG2, IgA, and IgE ratios were greater than that in plasma, suggesting there is local antibody secretion at the dermis. Local Ig transcription was concentrated at the inner rather than the outer foreskin, and inner foreskin Ig ratios did not correlate with blood, indicating that localized production can contribute to the foreskin response. IgM, IgG1, IgG3, and IgA have preferential access to the foreskin epidermis, whereas IgG2, IgG4, and IgE are restricted to the dermis. Lastly, Ad5-specific IgA was selectively present in the colon, whereas foreskin Ad5 IgG was mainly derived from blood, and reached the inner epidermis at higher ratios than the outer (P<0.002). In summary, the foreskin antibody response combines local and systemic sources, and there is selective isotype accumulation in the epidermis. PMID:26509877

  4. Evaluation of IgG concentration and IgG subisotypes in foals with complete or partial failure of passive transfer after administration of intravenous serum or plasma.

    PubMed

    McClure, J T; DeLuca, J L; Lunn, D P; Miller, J

    2001-11-01

    The purpose of this study was to evaluate the ability of an equine plasma product i.v. and a concentrated serum product i.v. to deliver antibodies to 46 foals with failure of passive transfer (FPT). Treatment of FPT was as per manufacturers recommendations, using plasma (950 ml/unit) or a concentrated serum product (250 ml/unit). Significant variables affecting the 3 day post-transfusion serum immunoglobulin G (IgG) concentration of foals included body weight, pretransfusion IgG concentration, number of product units transfused, foaling season and product administered. Plasma treatment had a greater increase in post-transfusion serum IgG concentrations compared to the serum product treatment mainly because plasma contained approximately twice the amount of IgG per unit as the serum product. The change in equine influenza virus and tetanus toxoid-specific IgGa, IgGb, and IgG(T) titres was measured in foals from pretransfusion to 3 days post-transfusion. For each gram of IgG transfused, the change in antigen-specific IgG subisotypes were similar for both treatment groups. The results of this study suggest that similar foal serum IgG concentrations can be achieved 3 days post-transfusion by administering 1 unit of plasma or 2-3 units of serum product. PMID:11770990

  5. Isolated Mass-Forming IgG4-Related Cholangitis as an Initial Clinical Presentation of Systemic IgG4-Related Disease

    PubMed Central

    Kim, Seokhwi; Bae, Hyunsik; Choi, Misun; Kim, Binnari; Heo, Jin Seok; Kim, Ho Seong; Choi, Seung Hee; Jang, Kee-Taek

    2016-01-01

    IgG4-related disease (IgG4-RD) may involve multiple organs. Although it usually presents as diffuse organ involvement, localized mass-forming lesions have been occasionally encountered in pancreas. However, the same pattern has been seldom reported in biliary tract. A 61-year-old male showed a hilar bile duct mass with multiple enlarged lymph nodes in imaging studies and he underwent trisectionectomy under impression of cholangiocarcinoma. Gross examination revealed a mass-like lesion around hilar bile duct. Histopathologically, dense lymphoplasmacytic infiltration and storiform fibrosis were identified without evidence of malignancy. Immunohistochemical stain demonstrated rich IgG4-positive plasma cell infiltration. Follow-up imaging studies disclosed multiple enlarged lymph nodes with involvement of pancreas and perisplenic soft tissue. The lesions have been significantly reduced after steroid treatment, which suggests multi-organ involvement of systemic IgG4-RD. Here, we report an unusual localized mass-forming IgG4-related cholangitis as an initial presentation of IgG4-RD, which was biliary manifestation of systemic IgG4-related autoimmune disease. PMID:26755360

  6. In Men at Risk of HIV Infection, IgM, IgG1, IgG3 and IgA Reach the Human Foreskin Epidermis

    PubMed Central

    Lemos, Maria P.; Karuna, Shelly T.; Mize, Gregory J.; Fong, Youyi; Montano, Silvia M.; Ganoza, Carmela; Lama, Javier R.; Sanchez, Jorge; McElrath, M. Juliana

    2015-01-01

    We profiled the humoral response in the penis, an area that has been minimally explored but may be relevant for protecting insertive men against HIV and other sexually-acquired infections. Comparing paired tissue samples from 20 men at risk of HIV infection, foreskin contains less IgA and more IgG2 than colon. Using foreskin dermal and epidermal explants and paired plasma from 17 men, we examined Ig accumulation by normalizing Ig to human serum albumin (HSA) transudation. Dermal IgM, IgG2, IgA, and IgE ratios were greater than in plasma, suggesting there is local antibody secretion at the dermis. Local Ig transcription was concentrated at the inner rather than the outer foreskin, and inner foreskin Ig ratios did not correlate with blood, indicating that localized production can contribute to the foreskin response. IgM, IgG1, IgG3, and IgA have preferential access to the foreskin epidermis, whereas IgG2, IgG4, and IgE are restricted to the dermis. Lastly, Ad5-specific IgA was selectively in the colon; whereas foreskin Ad5 IgG was mainly derived from blood, and reached the inner epidermis at higher ratios than the outer (p<0.002). In summary, the foreskin antibody response combines local and systemic sources and there is selective isotype accumulation in the epidermis. PMID:26509877

  7. Purified IgG from Patients with Obstetric but not IgG from Non-obstetric Antiphospholipid Syndrome Inhibit Trophoblast Invasion

    PubMed Central

    Poulton, Katie; Ripoll, Vera M; Pericleous, Charis; Meroni, Pier Luigi; Gerosa, Maria; Ioannou, Yiannis; Rahman, Anisur; Giles, Ian P

    2015-01-01

    Problem Some patients with antiphospholipid syndrome (APS) suffer pregnancy morbidity (PM) but not vascular thrombosis (VT), whilst others suffer VT only. Therefore, we compared the effects of IgG from VT+/PM− and VT−/PM+ subjects on human first-trimester trophoblast (HTR8) cells. Method of study HTR-8 cells were incubated with APS VT+/PM−, APS VT−/PM+ or healthy control (HC) IgG. We measured trophoblast invasion by cell invasion assay; mRNA expression of TLR4 and adaptor proteins; phosphorylation of p38 MAPK, NFκB and ERK; and expression of interleukin (IL)-8 and IL-6. Results VT−/PM+ IgG, but not VT+/PM− IgG significantly reduced HTR-8 invasion. The effects on invasion were blocked by TLR-4 inhibition. Neither VT+/PM− nor VT−/PM+ IgG altered MyD88 mRNA expression, phosphorylation of signalling molecules or cytokine expression. Conclusions VT−/PM+ IgG exert functionally relevant effects on human trophoblast cells but VT+/PM− IgG do not. PMID:25469631

  8. Pattern and concentration of IgG in cerebrospinal fluid in neurosarcoidosis.

    PubMed

    Scott, T F; Seay, A R; Goust, J M

    1989-12-01

    Reports have suggested that the pattern of CSF IgG differentiates neurosarcoidosis from multiple sclerosis. We examined CSF and serum of 7 patients with neurosarcoidosis to determine concentrations of IgG and albumin and the presence of oligoclonal bands. Our results showed that neurosarcoidosis may have associated abnormalities of IgG synthesis and oligoclonal bands present in CSF, but without a consistent pattern. PMID:2586781

  9. Corticosteroid Therapy for a Patient with Relapsing Polychondritis Complicated by IgG4-Related Disease.

    PubMed

    Yamasue, Mari; Nureki, Shin-Ichi; Matsumoto, Hiroyuki; Kan, Takamasa; Hashimoto, Takehiro; Ushijima, Ryoichi; Usagawa, Yuko; Kadota, Jun-Ichi

    2016-01-01

    Relapsing polychondritis (RP) is a rare systemic disorder characterized by recurrent, widespread chondritis of the auricular, nasal, and tracheal cartilages. IgG4-related disease (IgG4-RD) is a systemic immune-mediated disease characterized by the infiltration of IgG4-bearing plasma cells into systemic organs. Although 25% to 35% of patients with RP have a concurrent autoimmune disease, coexistence of RP and IgG4-RD is rare. We herein report a case of RP complicated by IgG4-RD. A 63-year-old man developed recurrent bilateral ear pain and swelling, recurrent blurred and decreased vision, and migratory multiple joint pain, sequentially within one year. Fourteen months after the first symptom, he experienced dry cough and dyspnea with exertion. A computed tomography (CT) scan detected interstitial pneumonia, swelling of bilateral submandibular glands, bilateral hilar and mediastinal lymphadenopathy, and several nodules in bilateral kidneys. His serum levels of IgG and IgG4 were elevated. The biopsy specimen of auricular cartilage showed infiltrations of inflammatory cells and fibrosis consistent with RP. The IgG4-positive cells were not observed in auricular cartilage. The patient met the diagnostic criteria of RP, including bilateral auricular chondritis, conjunctivitis, iritis and polyarthritis. The biopsy specimens of lung and kidney revealed the significant infiltrations of IgG4-positive plasma cells and fibrosis. We also diagnosed him as having IgG4-RD, affecting bilateral submandibular glands, hilar and mediastinal lymph nodes, lungs, and kidneys. Thus, RP preceded the onset of IgG4-RD. Corticosteroid therapy improved the symptoms and CT scan findings. In conclusion, RP and IgG4-RD do coexist; however, the pathogenesis of their coexistence is unknown. PMID:27396510

  10. Mitochondrial-dependent Autoimmunity in Membranous Nephropathy of IgG4-related Disease

    PubMed Central

    Buelli, Simona; Perico, Luca; Galbusera, Miriam; Abbate, Mauro; Morigi, Marina; Novelli, Rubina; Gagliardini, Elena; Tentori, Chiara; Rottoli, Daniela; Sabadini, Ettore; Saito, Takao; Kawano, Mitsuhiro; Saeki, Takako; Zoja, Carlamaria; Remuzzi, Giuseppe; Benigni, Ariela

    2015-01-01

    The pathophysiology of glomerular lesions of membranous nephropathy (MN), including seldom-reported IgG4-related disease, is still elusive. Unlike in idiopathic MN where IgG4 prevails, in this patient IgG3 was predominant in glomerular deposits in the absence of circulating anti-phospholipase A2 receptor antibodies, suggesting a distinct pathologic process. Here we documented that IgG4 retrieved from the serum of our propositus reacted against carbonic anhydrase II (CAII) at the podocyte surface. In patient's biopsy, glomerular CAII staining increased and co-localized with subepithelial IgG4 deposits along the capillary walls. Patient's IgG4 caused a drop in cell pH followed by mitochondrial dysfunction, excessive ROS production and cytoskeletal reorganization in cultured podocytes. These events promoted mitochondrial superoxide-dismutase-2 (SOD2) externalization on the plasma membrane, becoming recognizable by complement-binding IgG3 anti-SOD2. Among patients with IgG4-related disease only sera of those with IgG4 anti-CAII antibodies caused low intracellular pH and mitochondrial alterations underlying SOD2 externalization. Circulating IgG4 anti-CAII can cause podocyte injury through processes of intracellular acidification, mitochondrial oxidative stress and neoantigen induction in patients with IgG4 related disease. The onset of MN in a subset of patients could be due to IgG4 antibodies recognizing CAII with consequent exposure of mitochondrial neoantigen in the context of multifactorial pathogenesis of disease. PMID:26137589

  11. Glomerular lesions induced in the rabbit by physicochemically altered homologous IgG.

    PubMed Central

    Cavalot, F.; Miyata, M.; Vladutiu, A.; Terranova, V.; Dubiski, S.; Burlingame, R.; Tan, E.; Brentjens, J.; Milgrom, F.; Andres, G.

    1992-01-01

    Immunization of rabbits with physicochemically altered homologous or even autologous IgG induces formation of antibodies combining with IgG of rabbit and of foreign species. Cardiac but not renal lesions were reported in such animals. This study examined the nephritogenic potential of the immune response to cationized or heat-aggregated homologous IgG of b9 or b4 allotype in rabbits of the b4 allotype. Rabbits injected with either b9 or b4 cationized IgG produced antibodies reactive with rabbit and human IgG and with histones; they also developed abnormal glomerular deposits of IgG b4 and C3 corresponding to alterations of the glomerular basement membranes (GBM). Rabbits injected with either b9 or b4 aggregated IgG developed antibodies reactive with rabbit and human IgG and abnormal glomerular deposits of IgG b4 and C3 in the GBM and in the mesangium with subendothelial and mesangial electron-dense deposits. Some rabbits in both groups had proliferative and exudative glomerulonephritis and proteinuria. The results showed that immunization of rabbits with physicochemically altered homologous IgG induces an immune response to rabbit and human IgG and to histones as well as glomerular deposits of autologous IgG and C3 and other glomerular lesions. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 11 Figure 12 Figure 13 Figure 14 Figure 15 Figure 16 Figure 17 Figure 18 Figure 19 Figure 20 Figure 21 Figure 22 Figure 23 Figure 24 Figure 25 Figure 26 Figure 27 Figure 28 Figure 29 Figure 30 PMID:1546743

  12. Pulmonary inflammatory myofibroblastic tumor and IgG4-related inflammatory pseudotumor: a diagnostic dilemma.

    PubMed

    Bhagat, Priyanka; Bal, Amanjit; Das, Ashim; Singh, Navneet; Singh, Harkant

    2013-12-01

    IgG4-related inflammatory pseudotumor (IPT) and inflammatory myofibroblastic tumor (IMT) share morphological features like a prominent fibroblastic/myofibroblastic proliferation and the presence of inflammatory cells. Since IPT is managed conservatively and IMT is treated by surgical excision, it is important to differentiate these two lesions. The aim of this study is to highlight morphological and immunohistochemical features that distinguish IPT and IMT. Clinicopathological characteristics of cases diagnosed as pulmonary IPT or IMT from 1997 to 2013 were reviewed. The histological features were studied on hematoxylin and eosin-stained sections. Immunohistochemistry was done for IgG, IgG4, ALK-1, SMA, desmin, and CD34 for classification into IPT and IMT. Of the ten patients, seven were male and the age ranged from 4 to 58 years. The tumor size ranged from 1.5 to 4.0 cm in diameter. Histologically, proliferation of bland-looking spindle cells along with fibrosis and an inflammatory infiltrate comprising of lymphocytes and plasma cells were the common morphological features of both lesions. The spindle cell proliferation was more marked in IMT whereas lymphoplasmacytic infiltrate was more prominent in IPT. Obstructive phlebitis was observed only in cases of IPT. IgG4 expression was noted in IPT, and the number of IgG4-positive plasma cells and the ratio of IgG4+/IgG+ plasma cells were significantly lower in IMT than in IgG4-related IPT. Expression of anaplastic lymphoma kinase (ALK) was observed only in IMT, but not in IgG4-related IPT. The proportion of proliferating spindle cells, lymphoplasmacytic infiltrate, obstructive phlebitis, IgG4+ plasma cells and the ratio of IgG4+/IgG+ plasma cells, and ALK expression are helpful in differentiating these morphologically similar but biologically different lesions, which require different treatment modalities. PMID:24100523

  13. Structure and antigenicity analysis of the IgG gene for Nyctereutes procyonoides

    PubMed Central

    Zhao, Cui; Guo, Shuyuan; Pang, Xiaoru; Song, Daozhen; Fu, Shijun

    2015-01-01

    Objective Nyctereutes procyonoides immunoglobulin G (IgG) gene is partially cloned. Material and methods In order to obtain a certain length (966bp) of Nyctereutes procyonoides immunoglobulin G (IgG), two pairs of primers are designed according to the conserved nucleotide sequence of canine (GenBank:AF354265, AF354265, AF354266, AF354267) and mink (GenBank: L07789). Using Bioinformatics technology and Western-blot to analyze antigenicity of Nyctereutes procyonoides IgG-B gene. Results The homology for nucleotide sequence of IgG between Nyctereutes procyonoides and canine (IgG A, IgG B, IgG C, IgG D), mink, Homo sapiens, Oryctolagus cuniculus, Mus musculus, Anas platyrhynchos and gallus were respectively (88.1%, 93.6%, 85.4%, 87.2%), 83.7%, 74.8%, 71.8%, 69.2%, 51.6%, 48.4%. It can be seen that there was high homology of aminoacid sequence between IgG of Nyctereutes procyonoides and IgG (A, B, C, D) of canine. And the serum antibody of Nyctereutes procyonoides had obviously cross-reaction with HRP conjugated rabbit anti-dog IgG, compared with those of canine, oryctolagus cuniculus, mus musculus, mink, gallus. Conclusions We successfully got Nyctereutes procyonoides immuneglobulin G (IgG) gene (Gen- Bank: KM010191). There is the closest ties of consanguinity of IgG exist between Nyctereutes procyonoides and canine among the mammal through the genetic evolution. The detection and treament of canine distemper can be used on Nyctereutes procyonoides. PMID:26648768

  14. Acid-induced aggregation of human monoclonal IgG1 and IgG2: molecular mechanism and the effect of solution composition.

    PubMed

    Hari, Sanjay B; Lau, Hollis; Razinkov, Vladimir I; Chen, Shuang; Latypov, Ramil F

    2010-11-01

    The prevention of aggregation in therapeutic antibodies is of great importance to the biopharmaceutical industry. In our investigation, acid-induced aggregation of monoclonal IgG1 and IgG2 antibodies was studied at pH 3.5 as a function of salt concentration and buffer type. The extent of aggregation was estimated using a native cation-exchange chromatography (CEX) method based on the loss of soluble monomer. This approach allowed quantitative analysis of antibody aggregation kinetics for individual and mixed protein solutions. Information regarding the aggregation mechanism was gained by assessing stabilities of intact antibodies relative to their Fc and Fab fragments. The role of protein thermodynamic stability in aggregation was deduced from differential scanning calorimetry (DSC). The rate of aggregation under conditions mimicking the viral inactivation step during monoclonal antibody (mAb) processing was found to be strongly dependent on the antibody subclass (IgG1 vs IgG2). At 25 °C, IgG1s were resistant to low pH aggregation, but IgG2s aggregated readily in the presence of salt. The observed distinction between IgG1 and IgG2 aggregation resulted from differential stability of the corresponding C(H)2 domains. This was further confirmed by experimenting with an IgG1 molecule containing an aglycosylated C(H)2 domain. Interestingly, comparative analysis of two buffer systems (based on acetic acid vs citric acid) revealed differences in mAb aggregation under identical pH conditions. Evidence is provided for the importance of the total acid concentration for antibody aggregation at low pH. The effects of C(H)2 instability and solution composition on aggregation are significant and deserve careful consideration during the development of mAb- or Fc-based therapeutics. PMID:20843079

  15. Improved tumor imaging and therapy via i.v. IgG–mediated time-sequential modulation of neonatal Fc receptor

    PubMed Central

    Singh Jaggi, Jaspreet; Carrasquillo, Jorge A.; Seshan, Surya V.; Zanzonico, Pat; Henke, Erik; Nagel, Andrew; Schwartz, Jazmin; Beattie, Brad; Kappel, Barry J.; Chattopadhyay, Debjit; Xiao, Jing; Sgouros, George; Larson, Steven M.; Scheinberg, David A.

    2007-01-01

    The long plasma half-life of IgG, while allowing for enhanced tumor uptake of tumor-targeted IgG conjugates, also results in increased background activity and normal-tissue toxicity. Therefore, successful therapeutic uses of conjugated antibodies have been limited to the highly sensitive and readily accessible hematopoietic tumors. We report a therapeutic strategy to beneficially alter the pharmacokinetics of IgG antibodies via pharmacological inhibition of the neonatal Fc receptor (FcRn) using high-dose IgG therapy. IgG-treated mice displayed enhanced blood and whole-body clearance of radioactivity, resulting in better tumor-to-blood image contrast and protection of normal tissue from radiation. Tumor uptake and the resultant therapeutic response was unaltered. Furthermore, we demonstrated the use of this approach for imaging of tumors in humans and discuss its potential applications in cancer imaging and therapy. The ability to reduce the serum persistence of conjugated IgG antibodies after their infusion can enhance their therapeutic index, resulting in improved therapeutic and diagnostic efficacy. PMID:17717602

  16. Improved tumor imaging and therapy via i.v. IgG-mediated time-sequential modulation of neonatal Fc receptor.

    PubMed

    Jaggi, Jaspreet Singh; Carrasquillo, Jorge A; Seshan, Surya V; Zanzonico, Pat; Henke, Erik; Nagel, Andrew; Schwartz, Jazmin; Beattie, Brad; Kappel, Barry J; Chattopadhyay, Debjit; Xiao, Jing; Sgouros, George; Larson, Steven M; Scheinberg, David A

    2007-09-01

    The long plasma half-life of IgG, while allowing for enhanced tumor uptake of tumor-targeted IgG conjugates, also results in increased background activity and normal-tissue toxicity. Therefore, successful therapeutic uses of conjugated antibodies have been limited to the highly sensitive and readily accessible hematopoietic tumors. We report a therapeutic strategy to beneficially alter the pharmacokinetics of IgG antibodies via pharmacological inhibition of the neonatal Fc receptor (FcRn) using high-dose IgG therapy. IgG-treated mice displayed enhanced blood and whole-body clearance of radioactivity, resulting in better tumor-to-blood image contrast and protection of normal tissue from radiation. Tumor uptake and the resultant therapeutic response was unaltered. Furthermore, we demonstrated the use of this approach for imaging of tumors in humans and discuss its potential applications in cancer imaging and therapy. The ability to reduce the serum persistence of conjugated IgG antibodies after their infusion can enhance their therapeutic index, resulting in improved therapeutic and diagnostic efficacy. PMID:17717602

  17. A special subtype of POEMS syndrome: IgG4 subtype

    PubMed Central

    Zheng, Miao; Zhou, Pan; Zheng, Kai; Meng, Li; Liu, Xian; Chu, Mengdi; Lu, Jie; Dong, Lingli

    2016-01-01

    Both POEMS syndrome and IgG4 related diseases are uncommon and clinical manifestations have been multifarious and nonspecific. There is still no literature describing the relationships between these two diseases. This study describes a case of a 33-year-old woman with POEMS syndrome, who had high serum IgG4 concentration and monoclonal IgG4 positive plasmacyte tissue infiltration. This is the first available report of the IgG4 subtype of POEMS syndrome. It is found that the best treatment is to find a novel therapy that targets the plasma cells directly. PMID:27158350

  18. Human immunoglobulin class and IgG subclass regulation: dual action of interleukin-4.

    PubMed

    Kotowicz, K; Callard, R E

    1993-09-01

    Epstein-Barr virus (EBV) was used as a polyclonal human B cell mitogen to investigate the regulation of immunoglobulin class and IgG subclass responses by interleukin-4 (IL-4). Activation of tonsillar B cells with EBV resulted in an early peak of polyclonal immunoglobulin secretion between days 13 and 14 consisting of IgM, IgA, and IgG1, IgG2, IgG3 and IgG4, but not IgE. Addition of IL-4 to EBV-activated B cells at concentrations of 100 U/ml or greater induced the production of IgE and enhanced IgG4 secretion, but had no effect, or more often inhibited the other isotypes. In contrast, low concentrations of IL-4 (1-5 U/ml) significantly increased the production of IgM, IgA, IgG1, IgG2 and IgG3, but had no effect on IgG4 or IgE. The increase in immunoglobulin secretion obtained with low concentrations of IL-4 was found to occur only with high-density (resting) B cells, suggesting that IL-4 was not functioning simply as a late-acting differentiation factor. Low concentrations of IL-4 significantly increased IgG1, IgG2, IgG3, and IgA production by surface (s) IgM+ (sIgG-/sIgA-) B cells which is consistent with heavy chain switching. In some experiments, however, IL-4 enhanced IgM secretion by sIgM+ B cells, and IgA, IgG1, IgG2, IgG3 by sIgM- B cells, suggesting that it may have an additional B cell differentiation factor activity which was not isotype specific. The different effect of IL-4 at high and low concentrations were similar to those observed in B cell activation experiments, and may be due to the existence of high- and low-affinity IL-4 receptors. PMID:8396532

  19. 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. PMID:8199463

  20. IgG4-related disease in the sinonasal cavity accompanied by intranasal structure loss.

    PubMed

    Inoue, Akiko; Wada, Kota; Matsuura, Kentaro; Osafune, Hiroshi; Ida, Yutaro; Kosakai, Arifumi; Edamatsu, Hideo

    2016-02-01

    IgG4-related disease was recently proposed under the classification of systemic chronic inflammatory disease. In the field of otolaryngology, organ-specific diagnostic criteria have been established for the occurrence of this condition in the salivary glands, but not in the sinonasal cavity. Here we report a case involving a 70-year-old man with IgG4-related disease in the sinonasal cavity. The patient, with the chief complaint of nasal bleeding, first visited a physician. However, the patient experienced recurrent bleeding with intranasal structure loss and was subsequently referred to our hospital. His IgG4 level was elevated, and histopathological examination of a tissue sample obtained from the edematous sphenoid sinus showed increased IgG4-positive plasma cells and storiform fibrosclerosis. A definitive diagnosis of IgG4-related rhinosinusitis was made on the basis of comprehensive criteria for IgG4-related disease. The disease showed a progressively destructive course that was clearly different from that of chronic sinusitis and represented a very rare case of IgG4-related rhinosinusitis. IgG4-related disease originating in the sinonasal cavity is rare, and, to the best of our knowledge, this is the first primary case of IgG4-related disease that originated in one side of the sinonasal cavity and showed progressive destruction. PMID:26104224

  1. IgG4- related disease: an orphan disease with many faces

    PubMed Central

    2014-01-01

    Immunoglobulin G4- related disease (IgG4-RD) is a rare systemic fibro-inflammatory disorder (ORPHA284264). Although patients have been described more than 100 years ago, the systemic nature of this disease has been recognized in the 21st century only. Type 1 autoimmune pancreatitis is the most frequent manifestation of IgG4-RD. However, IgG4-RD can affect any organ such as salivary glands, orbits, retroperitoneum and many others. Recent research enabled a clear clinical and histopathological description of IgG4-RD. Typically, lymphoplasmacellular inflammation, storiform fibrosis and obliterative phlebitis are found in IgG4-RD biopsies and the tissue invading plasma cells largely produce IgG4. Elevated serum IgG4 levels are found in many but not all patients. Consequently, diagnostic criteria for IgG4-RD have been proposed recently. Treatment is largely based on clinical experience and retrospective case series. Glucocorticoids are the mainstay of therapy, although adjunctive immunosuppressive agents are used in relapsing patients. This review summarizes current knowledge on clinical manifestations, pathophysiology and treatment of IgG4-RD. PMID:25026959

  2. IgG1 Fc N-glycan galactosylation as a biomarker for immune activation.

    PubMed

    de Jong, Sanne E; Selman, Maurice H J; Adegnika, Ayola A; Amoah, Abena S; van Riet, Elly; Kruize, Yvonne C M; Raynes, John G; Rodriguez, Alejandro; Boakye, Daniel; von Mutius, Erika; Knulst, André C; Genuneit, Jon; Cooper, Philip J; Hokke, Cornelis H; Wuhrer, Manfred; Yazdanbakhsh, Maria

    2016-01-01

    Immunoglobulin G (IgG) Fc N-glycosylation affects antibody-mediated effector functions and varies with inflammation rooted in both communicable and non-communicable diseases. Worldwide, communicable and non-communicable diseases tend to segregate geographically. Therefore, we studied whether IgG Fc N-glycosylation varies in populations with different environmental exposures in different parts of the world. IgG Fc N-glycosylation was analysed in serum/plasma of 700 school-age children from different communities of Gabon, Ghana, Ecuador, the Netherlands and Germany. IgG1 galactosylation levels were generally higher in more affluent countries and in more urban communities. High IgG1 galactosylation levels correlated with low total IgE levels, low C-reactive protein levels and low prevalence of parasitic infections. Linear mixed modelling showed that only positivity for parasitic infections was a significant predictor of reduced IgG1 galactosylation levels. That IgG1 galactosylation is a predictor of immune activation is supported by the observation that asthmatic children seemed to have reduced IgG1 galactosylation levels as well. This indicates that IgG1 galactosylation levels could be used as a biomarker for immune activation of populations, providing a valuable tool for studies examining the epidemiological transition from communicable to non-communicable diseases. PMID:27306703

  3. IgG1 Fc N-glycan galactosylation as a biomarker for immune activation

    PubMed Central

    de Jong, Sanne E.; Selman, Maurice H. J.; Adegnika, Ayola A.; Amoah, Abena S.; van Riet, Elly; Kruize, Yvonne C. M.; Raynes, John G.; Rodriguez, Alejandro; Boakye, Daniel; von Mutius, Erika; Knulst, André C.; Genuneit, Jon; Cooper, Philip J.; Hokke, Cornelis H.; Wuhrer, Manfred; Yazdanbakhsh, Maria

    2016-01-01

    Immunoglobulin G (IgG) Fc N-glycosylation affects antibody-mediated effector functions and varies with inflammation rooted in both communicable and non-communicable diseases. Worldwide, communicable and non-communicable diseases tend to segregate geographically. Therefore, we studied whether IgG Fc N-glycosylation varies in populations with different environmental exposures in different parts of the world. IgG Fc N-glycosylation was analysed in serum/plasma of 700 school-age children from different communities of Gabon, Ghana, Ecuador, the Netherlands and Germany. IgG1 galactosylation levels were generally higher in more affluent countries and in more urban communities. High IgG1 galactosylation levels correlated with low total IgE levels, low C-reactive protein levels and low prevalence of parasitic infections. Linear mixed modelling showed that only positivity for parasitic infections was a significant predictor of reduced IgG1 galactosylation levels. That IgG1 galactosylation is a predictor of immune activation is supported by the observation that asthmatic children seemed to have reduced IgG1 galactosylation levels as well. This indicates that IgG1 galactosylation levels could be used as a biomarker for immune activation of populations, providing a valuable tool for studies examining the epidemiological transition from communicable to non-communicable diseases. PMID:27306703

  4. Bicentric evaluation of Access Toxo immunoglobulin M (IgM) and IgG assays and IMx toxo IgM and IgG assays and comparison with Platelia Toxo IgM and IgG assays.

    PubMed Central

    Decoster, A; Lecolier, B

    1996-01-01

    The recent Access immunoanalysis system (Sanofi Diagnostics Pasteur) for the serological diagnosis of toxoplasmosis was compared with the Abbott Toxo IMx EIA system, taking the Platelia Toxo immunoglobulin G (IgG) and Platelia Toxo IgM systems as references and using as confirmation methods an indirect fluorescence assay or a dye test for IgG and an immunosorbent agglutination assay (ISAGA) for IgM. A total of 1,461 serum samples were studied, of which 128 were collected from 42 recently seroconverted patients. Sensitivity and specificity rates of the Access system were 97.7 and 99.5%, respectively, for IgM and 98.6 and 100%, respectively, for IgG. Sensitivity and specificity rates of the Abbott IMx EIA system were 91 and 100%, respectively, for IgM and 92.5 and 100%, respectively, for IgG. The Access Toxo IgG and IgM EIA systems were found to be more sensitive than the Abbott Toxo IgG and IgM IMx EIA systems. PMID:8784554

  5. Bacteriological culture of blood from critically ill neonatal calves.

    PubMed Central

    Fecteau, G; Van Metre, D C; Paré, J; Smith, B P; Higgins, R; Holmberg, C A; Jang, S; Guterbock, W

    1997-01-01

    The objectives of this study were to estimate the prevalence of bacteremia in critically ill, neonatal calves with severe diarrhea or depression, and to describe the variety of bacteria involved. Two studies were conducted in the summers of 1991 and 1993 involving 190 neonatal calves, 1-day to 19-days-old. Bacteremia was detected by blood culture in 31% (28/90) of calves in study 1, and in 24% (19/79) of ill calves and 0% (0/21) of control calves in study 2. Bacteria cultured from blood included Escherichia coli (51% of all isolates), other gram-negative enterics (25.5%), gram-negative anaerobes (5.9%), gram-positive cocci (11.8%), and gram-positive rods (5.9%). Among clinically ill calves, the average age was significantly lower in the blood culture-negative group (5.5 d) than in the blood culture-positive group (7.5 d) (P = 0.004). Mean serum IgG concentration was significantly (P = 0.0001) lower in blood culture-positive calves (1.146 g/L) than in blood culture-negative calves (3.077 g/L). The mortality rate was significantly (P < 0.0001) higher in the blood culture-positive group (57.4%) than in the blood culture-negative group (15.1%). Bacteremia appeared to be a frequent entity in this particular rearing situation. Early recognition of the problem, as well as appropriate treatment, may be beneficial in increasing survival rates. Results also support the need to address the failure of passive transfer of maternal antibodies to prevent bacteremia in calves. Images Figure 1. PMID:9028592

  6. Neonatal Hyperglycemia due to Transient Neonatal Diabetes Mellitus in Puerto Rico

    PubMed Central

    Fargas-Berríos, N.; García-Fragoso, L.; García-García, I.; Valcárcel, M.

    2015-01-01

    Neonatal hyperglycemia is a metabolic disorder found in the neonatal intensive care units. Neonatal diabetes mellitus (NDM) is a very uncommon cause of hyperglycemia in the newborn, occurring in 1 in every 400,000 births. There are two subtypes of neonatal diabetes mellitus: permanent neonatal diabetes mellitus (PNDM) and transient neonatal diabetes mellitus (TNDM). We describe a term, small for gestational age, female neonate with transient neonatal diabetes mellitus who presented with poor feeding tolerance and vomiting associated with hyperglycemia (385 mg/dL), glycosuria, and metabolic acidosis within the first 12 hours of life. The neonate was treated with intravenous insulin, obtaining a slight control of hyperglycemia. An adequate glycemia was achieved at 5 weeks of life. The molecular studies showed complete loss of maternal methylation at the TND differentially methylated region on chromosome 6q24. The etiology of this neonate's hyperglycemia was a hypomethylation of the maternal TND locus. A rare cause of neonatal diabetes mellitus must be considered if a neonate presents refractory hyperglycemia. To our knowledge, this is the first case reported in Puerto Rico of transient neonatal mellitus due to the uncommon mechanism of maternal hypomethylation of the TND locus. Its prevalence in Puerto Rico is unknown. PMID:26576310

  7. Neonatal Hyperglycemia due to Transient Neonatal Diabetes Mellitus in Puerto Rico.

    PubMed

    Fargas-Berríos, N; García-Fragoso, L; García-García, I; Valcárcel, M

    2015-01-01

    Neonatal hyperglycemia is a metabolic disorder found in the neonatal intensive care units. Neonatal diabetes mellitus (NDM) is a very uncommon cause of hyperglycemia in the newborn, occurring in 1 in every 400,000 births. There are two subtypes of neonatal diabetes mellitus: permanent neonatal diabetes mellitus (PNDM) and transient neonatal diabetes mellitus (TNDM). We describe a term, small for gestational age, female neonate with transient neonatal diabetes mellitus who presented with poor feeding tolerance and vomiting associated with hyperglycemia (385 mg/dL), glycosuria, and metabolic acidosis within the first 12 hours of life. The neonate was treated with intravenous insulin, obtaining a slight control of hyperglycemia. An adequate glycemia was achieved at 5 weeks of life. The molecular studies showed complete loss of maternal methylation at the TND differentially methylated region on chromosome 6q24. The etiology of this neonate's hyperglycemia was a hypomethylation of the maternal TND locus. A rare cause of neonatal diabetes mellitus must be considered if a neonate presents refractory hyperglycemia. To our knowledge, this is the first case reported in Puerto Rico of transient neonatal mellitus due to the uncommon mechanism of maternal hypomethylation of the TND locus. Its prevalence in Puerto Rico is unknown. PMID:26576310

  8. IgG4-related disease and its pathogenesis—cross-talk between innate and acquired immunity

    PubMed Central

    Nakajima, Akio; Nakamura, Takuji; Kawanami, Takafumi; Tanaka, Masao; Dong, Lingli; Kawano, Mitsuhiro

    2014-01-01

    IgG4-related disease (IgG4-RD) is a novel clinical entity proposed in Japan in the 21th century and is attracting strong attention over the world. The characteristic manifestations of IgG4-RD are increased serum IgG4 concentration and tumefaction by IgG4+ plasma cells. Although the clinical manifestations in various organs have been established, the pathogenesis of IgG4-RD is still unknown. Recently, many reports of aberrant acquired immunity such as Th2-diminated immune responses have been published. However, many questions still remain, including questions about the pathogenesis of IgG4-RD and the roles of IgG4. In this review, we discuss the pathogenesis of IgG4-RD by focusing on the cross-talk between innate and acquired immunity. PMID:25024397

  9. IgG4-related Orbital Disease and Its Mimics in a Western Population.

    PubMed

    Ferry, Judith A; Klepeis, Veronica; Sohani, Aliyah R; Harris, Nancy Lee; Preffer, Frederic I; Stone, John H; Grove, Arthur; Deshpande, Vikram

    2015-12-01

    Although chronic inflammatory disorders of the ocular adnexa are relatively common, their pathogenesis is in many cases poorly understood. Recent investigation suggests that many cases of sclerosing orbital inflammation are a manifestation of IgG4-related disease; however, most patients reported have been Asian, and it is not clear whether the results of studies from the Far East can be reliably extrapolated to draw conclusions about Western patients. We evaluated 38 cases previously diagnosed as orbital inflammatory pseudotumor or chronic dacryoadenitis to determine whether our cases fulfill the criteria for IgG4-RD (IgG4-related dacryoadenitis when involving the lacrimal gland, and IgG4-related sclerosing orbital inflammation when involving orbital soft tissue). Fifteen patients had IgG4-related dacryoadenitis or orbital inflammation. These patients included 9 men and 6 women, aged 24 to 77 years (median, 64 y). Lesions involved orbital soft tissue (8 cases), lacrimal gland (6 cases), and canthus (1 case). In 1 case, focal in situ follicular neoplasia was seen in a background of IgG4-RD. In another case, a clonal IGH gene rearrangement was detected. Four patients with IgG4-RD had evidence of IgG4-RD in other anatomic sites. Five patients, 1 man and 4 women, aged 26 to 74 years (median 50 y) had orbital lesions (2 involving lacrimal gland, 3 involving soft tissue) suspicious for, but not diagnostic of, IgG4-RD. Of 16 patients with IgG4-RD or probable IgG4-RD with information available regarding the course of their disease, 11 patients experienced recurrent or persistent orbital disease. However, no patient developed lymphoma, and no patient died of complications of IgG4-RD. Eighteen patients had lesions not representing IgG4-RD. They included 6 male and 12 female individuals aged 6 to 77 years (median, 47 y). These patients had a variety of diseases, including granulomatosis with polyangiitis (3 cases), Rosai-Dorfman disease (1 case), nonspecific chronic

  10. Anti-rhesus D prophylaxis in pregnant women is based on sialylated IgG antibodies

    PubMed Central

    Ehlers, Marc

    2013-01-01

    Red blood cells (RBCs) from a rhesus D (RhD)-positive fetus that reach the bloodstream of an RhD-negative pregnant woman during birth can induce a pathogenic antibody (Ab) response against the RhD-positive RBCs, leading to fetal hemolytic disease in subsequent pregnancies. To prevent a pathogenic immune reaction, the RhD-negative mother receives serum immunoglobulin G (IgG) containing polyclonal RhD-specific IgG Abs that is purified from healthy RhD-negative men immunized with RhD-positive RBCs. However, the protective mechanism of these polyclonal RhD-specific IgG Abs is unclear. It has become increasingly clear that the effector function of IgG Abs is regulated by the glycan pattern linked to the Fc region of IgG Abs. Non-fucosylated (afucosylated) IgG Abs have a higher affinity for activating Fc gamma receptors, and thus induce a stronger Ab-dependent cellular cytotoxicity (ADCC) reaction than do fucosylated IgG Abs. Agalactosylated and asialylated, autoantigen-specific serum IgG Abs correlate with pro-inflammatory immune responses and disease activity in patients with rheumatoid arthritis. In contrast, galactosylated and sialylated IgG Abs are immunosuppressive and inhibit in form of immune complexes (ICs) dendritic cell (DC) maturation and pro-inflammatory T and B cell immune responses in an antigen-specific manner. However, the galactosylation and sialylation levels of the protective polyclonal RhD-specific IgG Abs are unknown. Here, we purified RhD-specific IgG Abs from the approved commercial product Rhophylac® (CSL Behring) and found that these RhD-specific IgG Abs were even more galactosylated and sialylated than the total Rhophylac® IgG Abs. This result suggests that these galactosylated and sialylated polyclonal RhD-specific IgG Abs are immunosuppressive and induce tolerance against RhD, which would be in strong contrast to a low fucosylated, low galactosylated and low sialylated monoclonal RhD-specific IgG Ab developed to prevent fetal hemolytic

  11. Contactin-1 IgG4 antibodies cause paranode dismantling and conduction defects.

    PubMed

    Manso, Constance; Querol, Luis; Mekaouche, Mourad; Illa, Isabel; Devaux, Jérôme J

    2016-06-01

    Paranodal axoglial junctions formed by the association of contactin-1, contactin-associated protein 1, and neurofascin-155, play important functions in nerve impulse propagation along myelinated axons. Autoantibodies to contactin-1 and neurofascin-155 define chronic inflammatory demyelinating polyradiculoneuropathy subsets of patients with specific clinical features. These autoantibodies are mostly of the IgG4 isotype, but their pathogenicity has not been proven. Here, we investigated the mechanisms how IgG subclasses to contactin-1 affect conduction. We show that purified anti-contactin-1 IgG1 and IgG4 bind to paranodes. To determine whether these isotypes can pass the paranodal barrier, we incubated isolated sciatic nerves with the purified antibody or performed intraneural injections. We found that IgG4 diffused into the paranodal regions in vitro or after intraneural injections. IgG4 infiltration was slow and progressive. In 24 h, IgG4 accessed the paranode borders near the nodal lumen, and completely fill the paranodal segments by 3 days. By contrast, control IgG, anti-contactin-1 IgG1, or even anti-contactin-associated-protein-2 IgG4 did not pass the paranodal barrier. To determine whether chronic exposure to these antibodies is pathogenic, we passively transferred anti-contactin-1 IgG1 and IgG4 into Lewis rats immunized with P2 peptide. IgG4 to contactin-1, but not IgG1, induced progressive clinical deteriorations combined with gait ataxia. No demyelination, axonal degeneration, or immune infiltration were observed. Instead, these animals presented a selective loss of the paranodal specialization in motor neurons characterized by the disappearance of the contactin-associated protein 1/contactin-1/neurofascin-155 complex at paranodes. Paranode destruction did not affect nodal specialization, but resulted in a moderate node lengthening. The sensory nerves and dorsal root ganglion were not affected in these animals. Electrophysiological examination further

  12. Glomerular IgG deposition predicts renal outcome in patients with IgA nephropathy.

    PubMed

    Shin, Dong Ho; Lim, Beom Jin; Han, In Mi; Han, Seung Gyu; Kwon, Young Eun; Park, Kyoung Sook; Lee, Mi Jung; Oh, Hyung Jung; Park, Jung Tak; Han, Seung Hyeok; Kang, Shin-Wook; Yoo, Tae-Hyun

    2016-07-01

    Glomerular IgG deposition is frequently observed in patients with IgA nephropathy. However, the association between glomerular IgG deposition and progression of IgA nephropathy is uncertain. Six hundred and twenty-seven patients with biopsy-proven IgA nephropathy were recruited. Histological variables of the Oxford classification (Oxford-MEST) and the presence of glomerular IgG deposits were assessed. Renal progression defined as end-stage renal disease or 50% reduction in estimated glomerular filtration rate was analyzed using Kaplan-Meier methods and Cox regression analysis. Of the study population, 200 patients (31.9%) had glomerular IgG deposition on immunofluorescence staining. During a mean follow-up of 56.8±37.5 months, the rate of renal progression was significantly higher in the IgA nephropathy patients with glomerular IgG deposition compared with the IgA nephropathy patients without glomerular IgG deposition (39.8 vs 12.3 per 1000 patient-years; P<0.001). Of patients with IgG deposition, 178 (28.3%), 20 (3.2%), and 2 (0.3%) patients had mild, moderate, and marked glomerular IgG deposits, receptively. Kaplan-Meier analysis revealed that cumulative renal survival was significantly lower in IgA nephropathy patients with the higher intensity of glomerular IgG deposits (P<0.001). In addition, Cox regression analysis revealed that moderate and marked glomerular IgG deposits significantly predicted renal outcome independent of Oxford-MEST and clinical variables (HR, 2.97; 95% CI, 1.01-8.77; P=0.04). This study showed that that glomerular IgG deposition was independently associated with poor renal outcome in patient with IgA nephropathy. PMID:27102346

  13. IgG subclass deficiency and sinopulmonary bacterial infections in patients with alcoholic liver disease.

    PubMed

    Spinozzi, F; Cimignoli, E; Gerli, R; Agea, E; Bertotto, A; Rondoni, F; Grignani, F

    1992-01-01

    Abnormalities in IgG subclass distribution were sought in serum samples and bronchoalveolar lavage fluid from 15 patients with alcoholic liver disease to explain their increased susceptibility to bacterial respiratory infections. Serum IgG4 deficiency alone or in association with low IgG2 levels was revealed in approximately 30% of patients with alcoholic liver disease. This fact prompted us to further investigate the immunoglobulin concentrations in broncho-alveolar lavage fluid, paying special attention to the distribution of IgA and IgG subclasses. IgA levels were found to be normal or slightly elevated. However, there were substantial defects in total IgG and IgG1 concentrations, often associated with reduced IgG2 and IgG4 levels, in approximately 70% of patients with alcoholic liver disease, which proved to be closely correlated with the number and type (pneumonia) of bacterial respiratory infections. A prospective study of intravenous immunoglobulin substitutive therapy involving two patients with recurrent pneumonia and very low serum IgG2 values demonstrated a reduction in the number of respiratory infectious episodes as well as an increase in both serum and, to a lesser extent, bronchoalveolar lavage fluid IgG1 and IgG2 levels. We identified immune defects that may represent an important pathogenetic mechanism that, when considered together with the alcohol-related suppression of alveolar macrophage and ciliary functions and the inhibition of leukocyte migration into the lungs, should help clarify the complex relationships between alcohol and immune defense. PMID:1728935

  14. Clinical relevance of Küttner tumour and IgG4-related dacryoadenitis and sialoadenitis

    PubMed Central

    Furukawa, S; Moriyama, M; Kawano, S; Tanaka, A; Maehara, T; Hayashida, J-N; Goto, Y; Kiyoshima, T; Shiratsuchi, H; Ohyama, Y; Ohta, M; Imabayashi, Y; Nakamura, S

    2015-01-01

    Objectives Küttner tumour (KT), so-called chronic sclerosing sialoadenitis, is characterised by concomitant swelling of the submandibular glands secondary to strong lymphocytic infiltration and fibrosis independent of sialolith formation. However, recent studies have indicated that some patients with KT develop high serum levels of IgG4 and infiltration of IgG4-positive plasma cells, namely IgG4-related dacryoadenitis and sialoadenitis (IgG4-DS), so-called Mikulicz's disease. The aim of this study was to clarify the clinical and pathological associations between KT and IgG4-DS. Materials and Methods Fifty-four patients pathologically diagnosed with KT or chronic sialoadenitis were divided into two groups according to the presence or absence of sialolith (KT-S (+) or KT-S (−), respectively). Results There were no significant differences in the clinical findings, including the mean age, sex and disease duration, between the two groups. All patients in the KT-S (+) group showed unilateral swelling without infiltration of IgG4-positive plasma cells or a history of other IgG4-related diseases (IgG4-RD), while those in the KT-S (−) group showed bilateral swelling (37.5%), strong infiltration of IgG4-positive plasma cells (87.5%) and a history of other IgG4-RD (12.5%). Conclusions These results suggest an association between the pathogeneses of KT-S (−) and IgG4-DS, but not KT-S (+). PMID:24844187

  15. Separate Fc-receptors for immunoglogulins IgG2a and IgG2b on an established cell line of mouse macrophages.

    PubMed

    Walker, W S

    1976-04-01

    The specificity of Fe-receptors on IC-21 cells, an established line of mouse peritoneal macrophages with antibody-dependent effector cell activity has been examined. Only IgG2a and IgG2b myeloma proteins bound readily to IC-21 Fc-receptors, the former in nonaggregated as well as aggregated form, the latter only as aggregated complexes. Thus, IgG2a bound in a manner characteristic of classically defined cytophilic antibody, whereas the binding of IgG2b appeared to be mediated by Fc-receptors for antigen-antibody complexes. Evidence is presented in support of the view that IC-21 macrophages possess separate and distinct Fc-receptor sites for these two immunoglobulins. PMID:1254971

  16. A monoclonal antibody against hinge-cleaved IgG restores effector function to proteolytically-inactivated IgGs in vitro and in vivo

    PubMed Central

    Brezski, Randall J; Kinder, Michelle; Grugan, Katharine D; Soring, Keri L; Carton, Jill; Greenplate, Allison R; Petley, Theodore; Capaldi, Dorie; Brosnan, Kerry; Emmell, Eva; Watson, Sharon; Jordan, Robert E

    2014-01-01

    We report a chimeric monoclonal antibody (mAb) directed to a neo-epitope that is exposed in the IgG lower hinge following proteolytic cleavage. The mAb, designated 2095–2, displays specificity for IdeS-generated F(ab’)2 fragments, but not for full-length IgG or for closely-related F(ab’)2 fragments generated with other proteases. A critical component of the specificity is provided by the C-terminal amino acid of the epitope corresponding to gly-236 in the IgG1 (also IgG4) hinge. By its ability to bind to IdeS-cleaved anti-CD20 mAb, mAb 2095–2 fully restored antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against WIL2-S cells to the otherwise inactive anti-CD20 IgG1 F(ab’)2 fragment. Similarly, 2095–2 reinstated ADCC against MDA-MB-231 cells to an anti-CD142 IgG1 F(ab’)2 fragment. mAb 2095–2 was also capable of eliciting both CDC and ADCC to IgG4 F(ab’)2 fragments, an IgG subclass that has weaker ADCC and CDC when intact relative to intact IgG1. The in vitro cell-based efficacy of 2095–2 was extended to the in vivo setting using platelets as a cell clearance surrogate. In a canine model, the co-administration of 2095–2 together with IdeS-generated, platelet-targeting anti-CD41/61 F(ab’)2 fragment not only restored platelet clearance, but did so at a rate and extent of clearance that exceeded that of intact anti-CD41/61 IgG at comparable concentrations. To further explore this unexpected amplification effect, we conducted a rat study in which 2095–2 was administered at a series of doses in combination with a fixed dose of anti-CD41/61 F(ab’)2 fragments. Again, the combination, at ratios as low as 1:10 (w/w) 2095–2 to F(ab’)2, proved more effective than the anti-CD41/61 IgG1 alone. These findings suggest a novel mechanism for enhancing antibody-mediated cell-killing effector functions with potential applications in pathologic settings such as tumors and acute infections where protease

  17. A monoclonal antibody against hinge-cleaved IgG restores effector function to proteolytically-inactivated IgGs in vitro and in vivo.

    PubMed

    Brezski, Randall J; Kinder, Michelle; Grugan, Katharine D; Soring, Keri L; Carton, Jill; Greenplate, Allison R; Petley, Theodore; Capaldi, Dorie; Brosnan, Kerry; Emmell, Eva; Watson, Sharon; Jordan, Robert E

    2014-01-01

    We report a chimeric monoclonal antibody (mAb) directed to a neo-epitope that is exposed in the IgG lower hinge following proteolytic cleavage. The mAb, designated 2095-2, displays specificity for IdeS-generated F(ab')₂ fragments, but not for full-length IgG or for closely-related F(ab')₂ fragments generated with other proteases. A critical component of the specificity is provided by the C-terminal amino acid of the epitope corresponding to gly-236 in the IgG1 (also IgG4) hinge. By its ability to bind to IdeS-cleaved anti-CD20 mAb, mAb 2095-2 fully restored antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against WIL2-S cells to the otherwise inactive anti-CD20 IgG1 F(ab')₂ fragment. Similarly, 2095-2 reinstated ADCC against MDA-MB-231 cells to an anti-CD142 IgG1 F(ab')₂ fragment. mAb 2095-2 was also capable of eliciting both CDC and ADCC to IgG4 F(ab')₂ fragments, an IgG subclass that has weaker ADCC and CDC when intact relative to intact IgG1. The in vitro cell-based efficacy of 2095-2 was extended to the in vivo setting using platelets as a cell clearance surrogate. In a canine model, the co-administration of 2095-2 together with IdeS-generated, platelet-targeting anti-CD41/61 F(ab')₂ fragment not only restored platelet clearance, but did so at a rate and extent of clearance that exceeded that of intact anti-CD41/61 IgG at comparable concentrations. To further explore this unexpected amplification effect, we conducted a rat study in which 2095-2 was administered at a series of doses in combination with a fixed dose of anti-CD41/61 F(ab')₂ fragments. Again, the combination, at ratios as low as 1:10 (w/w) 2095-2 to F(ab')₂, proved more effective than the anti-CD41/61 IgG1 alone. These findings suggest a novel mechanism for enhancing antibody-mediated cell-killing effector functions with potential applications in pathologic settings such as tumors and acute infections where protease activity is

  18. Neonatal Pustular Dermatosis: An Overview

    PubMed Central

    Ghosh, Sangita

    2015-01-01

    Neonatal pustular eruption is a group of disorders characterized by various forms of pustulosis seen in first 4 weeks of life. Its presentation is often similar with some subtle differences, which can be further established by few simple laboratory aids, to arrive at a definite diagnosis. Given their ubiquitous presentation, it is sometimes difficult to differentiate among self-limiting, noninfectious, pustular dermatosis such as erythema toxicum neonatorum, transient neonatal pustular melanosis, miliaria pustulosa, etc., and potentially life threatening infections such as herpes simplex virus and varicella zoster virus infections. This review article tries to address the chronological, clinical, morphological, and histological differences among the various pustular eruptions in a newborn, in order to make it easier for a practicing dermatologist to diagnose and treat these similar looking but different entities of pustulation with a clear demarcation between the physiological benign pustular rashes and the infectious pustular lesions. PMID:25814724

  19. Pain Perception in the Neonate

    PubMed Central

    Midmer, Deana K.

    1989-01-01

    Pain expression in both pre-term and term infants is a little understood phenomenon. Recent research has generated data documenting that the newborn can feel pain, can act to avoid the pain, and may form memory traces of the experience. ”Nociceptive activity” or ”noxious stimuli” are better terms to use when addressing aversive stimulation of the neonate because they encourage scrutiny of the behavioural and physiologic responses of the newborn without placing emphasis on the emotional and subjective associations of the word ”pain”. Many invasive procedures are performed on infants with little or no provision for adequate pain management. The general and specific responses of the neonate to pain must be recognized. Analgesia and anesthesia should be made available to all infants, pre-term or term, sick or well, on the same basis on which they are made available to older children and adults. PMID:21248938

  20. Neonatal haemochromatosis associated with gastroschisis.

    PubMed

    Thornton, M P; Marven, S S; Tanner, M S; Gürtl-Lackner, B

    2008-05-01

    We describe, to our knowledge, the first case of progressive neonatal liver failure due to neonatal haemochromatosis (NH) occurring in an infant with a gastroschisis and review the literature regarding these two conditions. A 1,665 g male infant with antenatally diagnosed gastroschisis was born with a severe coagulopathy, anaemia, thrombocytopenia, hypoglycaemia and jaundice. He developed progressive liver failure, complicated by necrotising enterocolitis. Serum ferritin was elevated at 1,459 microg/L. He died on day 40 and a limited post-mortem examination confirmed significant hepatic siderosis with fibrosis and cholestasis, and siderosis of the pancreas. Although no genetic aetiology for gastroschisis has been identified, an occasional inherited tendency has been observed. There is also evidence to support an autosomal recessive inheritance in NH. PMID:18338135

  1. Neuroimaging in Neonatal Hypoxic Ischemic Encephalopathy.

    PubMed

    Krishnan, Pradeep; Shroff, Manohar

    2016-09-01

    Magnetic resonance (MR) imaging is emerging as one of the most important tools in identifying the etiology of neonatal encephalopathy as well as in predicting long-term outcomes. This makes it imperative to have a broader understanding of normal myelination of the neonatal brain on MR imaging and to be familiar with the spectrum of imaging features in ischemic and non-ischemic neonatal encephalopathy. Hypoxic ischemic injury (HIE) is one of the most common causes of neonatal encephalopathy and imaging appearances are influenced by factors such as the stage of maturation of the neonatal brain and severity as well as duration of ischemic insult. Other common causes of neonatal encephalopathy include infectious diseases, congenital disorders and inborn errors of metabolism. PMID:26909496

  2. Fetal and Neonatal Alloimmune Thrombocytopenia

    PubMed Central

    Espinoza, J P; Caradeux, J; Norwitz, Errol R; Illanes, S E

    2013-01-01

    Fetomaternal alloimmune thrombocytopenia (FMAIT) is a relatively uncommon disease, but is the leading cause of severe thrombocytopenia in the newborn. It can cause severe complications and long-term disabilities. The main objective of screening is to reduce both the morbidity and mortality associated with FMAIT, primarily by preventing intracranial hemorrhage. However, controversy surrounds both pre- and antenatal management. This article discusses pathogenesis, screening, diagnosis, and both pre- and neonatal management of FMAIT. PMID:23687553

  3. [A neonate with ambiguous genitalia].

    PubMed

    Jansen, Burgo J; van Rijn, Rick R; van Trotsenburg, A S P Paul

    2015-01-01

    In a neonate with ambiguous genitalia, physical examination revealed a phallus. Ultrasonography showed a vagina and uterus, but no gonads. Because of severe undervirilisation in the presence of a uterus, probably due to 46,XY gonadal dysgenesis, parents were advised female sex assignment. When after a few weeks the phallus had increased in size, abdominal laparoscopy showed an underdeveloped uterus. Gonadal biopsy confirmed gonadal dysgenesis. Sex assignment was reconsidered and changed into the male gender. PMID:26200425

  4. Neonatal resuscitation: improving the outcome.

    PubMed

    Davidson, Autumn P

    2014-03-01

    Prudent veterinary intervention in the prenatal, parturient, and postpartum periods can increase neonatal survival by controlling or eliminating factors contributing to puppy morbidity and mortality. Postresuscitation or within the first 24 hours of a natural delivery, a complete physical examination should be performed by a veterinarian, technician, or knowledgeable breeder. Adequate ingestion of colostrum must occur promptly (within 24 hours) postpartum for puppies and kittens to acquire passive immunity. PMID:24580986

  5. Early-Onset Neonatal Sepsis

    PubMed Central

    Simonsen, Kari A.; Anderson-Berry, Ann L.; Delair, Shirley F.

    2014-01-01

    SUMMARY Early-onset sepsis remains a common and serious problem for neonates, especially preterm infants. Group B streptococcus (GBS) is the most common etiologic agent, while Escherichia coli is the most common cause of mortality. Current efforts toward maternal intrapartum antimicrobial prophylaxis have significantly reduced the rates of GBS disease but have been associated with increased rates of Gram-negative infections, especially among very-low-birth-weight infants. The diagnosis of neonatal sepsis is based on a combination of clinical presentation; the use of nonspecific markers, including C-reactive protein and procalcitonin (where available); blood cultures; and the use of molecular methods, including PCR. Cytokines, including interleukin 6 (IL-6), interleukin 8 (IL-8), gamma interferon (IFN-γ), and tumor necrosis factor alpha (TNF-α), and cell surface antigens, including soluble intercellular adhesion molecule (sICAM) and CD64, are also being increasingly examined for use as nonspecific screening measures for neonatal sepsis. Viruses, in particular enteroviruses, parechoviruses, and herpes simplex virus (HSV), should be considered in the differential diagnosis. Empirical treatment should be based on local patterns of antimicrobial resistance but typically consists of the use of ampicillin and gentamicin, or ampicillin and cefotaxime if meningitis is suspected, until the etiologic agent has been identified. Current research is focused primarily on development of vaccines against GBS. PMID:24396135

  6. Strategies to reduce neonatal mortality.

    PubMed

    Singh, M

    1990-01-01

    In India, 60% of deaths in infants under 1 year of age occur in the 1st 4 weeks after birth. The neonatal mortality rate is currently 76/1000 live births in rural areas and 39/1000 in urban areas. The Government if India has launched a plan of action of address the cycle of poorly spaced pregnancies, inadequate maternal health care and nutrition, and high incidence of low birthweight babies that contributes to this high neonatal mortality phenomenon. Crucial to such a plan is the expansion, strengthening, and improved organization of maternal-child health services. At the level of maternal health services, efforts will be made to identify pregnant women early, arrange a minimum of 4 prenatal visits, provide dietary supplementation and immunization against tetanus toxoid, create more sterile conditions for home deliveries, identify and refer high-risk pregnancies and deliveries, and provide postnatal follow-up care. Child health service staff are motivating mothers to breastfeed and screening newborns for jaundice and bacterial infection. A risk approach, in which there is a minimum necessary level of care for all pregnant women but more intensive management and follow-up of those at high risk, is most cost-efficient given the lack of human and financial resources. Attention must also be given to the determinants of low birthweight (maternal undernutrition, closely spaced pregnancies, severe anemia, adolescent childbearing, prenatal infections, strenuous work responsibilities, and maternal hypertension), which is a co-factor in neonatal mortality. PMID:12316586

  7. Neonatal asphyxia and forensic medicine.

    PubMed

    d'Aloja, E; Müller, M; Paribello, F; Demontis, R; Faa, A

    2009-01-01

    In the last decades, the scientific literature addressing neonatal encephalopathy has grown in a logarithmic way and malpractice claims in obstetrics and neonatology have become a major threat to the health service. At the moment, scientific evidence are insufficient to clearly identify in each single case whether the hypoxic insult has developed in the course of labor or in the first few hours after the birth or, otherwise, whether the damage has to recognize a remote and long-lasting cause acting during pregnancy. Several authors feel that this scientific uncertainty leads to a higher percentage of civil suit decisions prone to recognizing a guilty medical behavior, and they wish a more in-depth analysis of all these cases to clearly identify all the data either in favor or in contrary to the assumption of the existence of a causal correlation between neonatal encephalopathy and medical misbehavior. This article will focus on the medico-legal approach to a hypoxic-ischemic event in the perinatal period, addressing the relevant data to be collected in order to establish the medical and juridical cause of the neonatal damage. PMID:19757333

  8. Bovine IgG subclasses and fertility of Echinococcus granulosus hydatid cysts.

    PubMed

    Riesle, Silke; García, María Pía; Hidalgo, Christian; Galanti, Norbel; Saenz, Leonardo; Paredes, Rodolfo

    2014-09-15

    Hydatidosis is an important zoonotic disease of worldwide distribution, causing important health problems to humans and major economical losses in infected livestock. Echinococcus granulosus, the etiological agent of hydatid disease, induces a humoral immune response in the intermediate host (human and herbivorous) against hydatid cyst antigens. Specifically, IgGs are found in the laminar and germinal layers and inside the lumen of fertile and infertile hydatid cysts. In the germinal layer of infertile cysts IgGs are found in an order of magnitude greater than in the germinal layer of fertile cysts; a fraction of those IgGs are associated with high affinity to germinal layer proteins, suggesting their binding to specific parasite antigens. We have previously shown that those immunoglobulins, bound with high affinity to the germinal layer of hydatid cysts, induce apoptosis leading to cyst infertility. In the present work the presence of IgG1 and IgG2 subclasses in the germinal layer of both fertile and infertile hydatid cysts is reported. IgG1 is the most relevant immunoglobulin subclass present in the germinal layer of infertile cysts and bound with high affinity to that parasite structure. Contrarily, though the IgG2 subclass was also found in the germinal and adventitial layers, those immunoglobulins show low affinity to parasite antigens. We propose that the binding of an IgG1 subclass to parasite antigens present in the germinal layer is involved in the mechanism of cyst infertility. PMID:24962125

  9. False-positive signals in enzyme immunoassay (EIA) interactions between rodent IgG subclasses.

    PubMed

    Pearce-Pratt, R; Roser, B

    1990-06-12

    Interactions between mouse and rat monoclonal antibodies (MAbs) in EIA have been detected using panels of mouse and rat MAbs of various isotypes. Mouse and rat antibodies of the IgG2a subclass were found to bind to each other most strongly. Immobilised IgG1 antibodies of the two species showed much less interaction. Rat IgG2b and IgG2c were intermediate in binding activity. We were unable to study examples of mouse IgG2b and IgG3 MAbs. By making use of the kappa light chain allotype in the rat we were also able to show intraspecies interactions of rat MAbs with the IgG in rat serum. The molecular basis of these interactions has not been resolved but may involve the extended hinge region and flexible Fab arms of the IgG2a subclass of Ig permitting strong inter domain bonding between the constant region domains of adjacent molecules of this isotype. PMID:2193060

  10. T cell–independent B cell activation induces immunosuppressive sialylated IgG antibodies

    PubMed Central

    Hess, Constanze; Winkler, André; Lorenz, Alexandra K.; Holecska, Vivien; Blanchard, Véronique; Eiglmeier, Susanne; Schoen, Anna-Lena; Bitterling, Josephine; Stoehr, Alexander D.; Petzold, Dominique; Schommartz, Tim; Mertes, Maria M.M.; Schoen, Carolin T.; Tiburzy, Ben; Herrmann, Anne; Köhl, Jörg; Manz, Rudolf A.; Madaio, Michael P.; Berger, Markus; Wardemann, Hedda; Ehlers, Marc

    2013-01-01

    Antigen-specific Abs are able to enhance or suppress immune responses depending on the receptors that they bind on immune cells. Recent studies have shown that pro- or antiinflammatory effector functions of IgG Abs are also regulated through their Fc N-linked glycosylation patterns. IgG Abs that are agalactosylated (non-galactosylated) and asialylated are proinflammatory and induced by the combination of T cell–dependent (TD) protein antigens and proinflammatory costimulation. Sialylated IgG Abs, which are immunosuppressive, and Tregs are produced in the presence of TD antigens under tolerance conditions. T cell–independent (TI) B cell activation via B cell receptor (BCR) crosslinking through polysaccharides or via BCR and TLR costimulation also induces IgG Abs, but the Fc glycosylation state of these Abs is unknown. We found in mouse experiments that TI immune responses induced suppressive sialylated IgGs, in contrast to TD proinflammatory Th1 and Th17 immune responses, which induced agalactosylated and asialylated IgGs. Transfer of low amounts of antigen-specific sialylated IgG Abs was sufficient to inhibit B cell activation and pathogenic immune reactions. These findings suggest an immune regulatory function for TI immune responses through the generation of immunosuppressive sialylated IgGs and may provide insight on the role of TI immune responses during infection, vaccination, and autoimmunity. PMID:23979161

  11. Experiences in the measurement of RBC-bound IgG as markers of cell age.

    PubMed

    Paleari, Renata; Ceriotti, Ferruccio; Azzario, Franco; Maccioni, Liliana; Galanello, Renzo; Mosca, Andrea

    2004-05-01

    An immunologically mediated pathway has been largely accepted to be one of the mechanisms involved in the clearance of senescent or prematurely damaged RBC. According to this pathway, RBC removal is mediated by binding of naturally occurring IgG to clustered integral membrane proteins, followed by complement deposition. The validation of an immunoenzymatic method for the detection of RBC-bound autologous IgG is presented. The use of RBC-bound IgG as an index related to red cell age was evaluated by measuring IgG binding in RBC treated with the clustering agent ZnCl2, in density fractionated RBC and in a selected group of patients expected to have an altered RBC life span. The immunoenzymatic method for IgG detection resulted to be reproducible (CV = 3.4%). IgG binding to in vitro clustered RBC was found to be enhanced to a very great extent, about 20 times higher with respect to untreated RBC. A slight but significant increase (about 1.8-fold) in membrane-bound IgG was observed in the highest density fraction of normal RBC, which constituted 1% of the total cells. A significantly greater number of RBC-bound IgG was measured in splenectomized beta-thalassemia intermedia patients and in subjects with secondary decreases in the C3 complement fraction concentration. PMID:15039023

  12. Peroxynitrite-induced structural perturbations in human IgG: A physicochemical study.

    PubMed

    Arfat, Mir Yasir; Arif, Zarina; Chaturvedi, Sumit Kumar; Moinuddin; Alam, Khursheed

    2016-08-01

    IgG is an important defence protein. To exhibit optimum function the molecule must maintain its native structure. Peroxynitrite is a potent oxidizing and nitrating agent produced in vivo under pathophysiological conditions. It can oxidize and/or nitrate various amino acids causing changes in the structure and function of proteins. Such proteins may be involved in the pathogenesis of many inflammatory diseases, including rheumatoid arthritis. In the present work, peroxynitrite-induced structural changes in IgG have been studied by UV-visible, fluorescence, CD, FT-IR, DLS spectroscopy and DSC as well as by SDS-PAGE. Peroxynitrite-modified IgG exhibited hyperchromicity at 280 nm, quenching of tryptophan fluorescence, increase in ANS fluorescence, loss of β-sheet, shift in the positions of amide I and amide II bands, appearance of new peak in FT-IR, attachment of nitro residues and increase in melting temperature, compared to native IgG. Furthermore, peroxynitrite-modified IgG exhibited an additional peak at 420 nm, quenching in tyrosine fluorescence and enhancement in dityrosine fluorescence compared to native IgG. Generation of nitrotyrosine, dityrosine and nitrotryptophan was also observed in peroxynitrite-modified IgG. Gross structural changes in IgG caused by peroxynitrite and observed in vitro may favour autoantibodies induction in vivo under similar conditions. PMID:27210739

  13. Enhanced HIV-1 neutralization by a CD4-VH3-IgG1 fusion protein

    SciTech Connect

    Meyuhas, Ronit; Noy, Hava; Fishman, Sigal; Margalit, Alon; Montefiori, David C.; Gross, Gideon

    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 on 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.

  14. Protease inhibitors decrease IgG shedding from Staphylococcus aureus, increasing complement activation and phagocytosis efficiency.

    PubMed

    Fernandez Falcon, Maria F; Echague, Charlene G; Hair, Pamela S; Nyalwidhe, Julius O; Cunnion, Kenji M

    2011-10-01

    Staphylococcus aureus is a major pathogen for immunologically intact humans and its pathogenesis is a model system for evasion of host defences. Antibodies and complement are essential elements of the humoral immune system for prevention and control of S. aureus infections. The specific hypothesis for the proposed research is that S. aureus modifies humoral host defences by cleaving IgG that has bound to the bacterial surface, thereby inhibiting opsonophagocytosis. S. aureus was coated with pooled, purified human IgG and assayed for the shedding of cleaved IgG fragments using ELISA and Western blot analysis. Surface-bound IgG was shed efficiently from S. aureus in the absence of host blood proteins. Broad-spectrum protease inhibitors prevented cleavage of IgG from the S. aureus surface, suggesting that staphylococcal proteases are responsible for IgG cleavage. Serine protease inhibitors and cysteine protease inhibitors decreased the cleavage of surface-bound IgG; however, a metalloprotease inhibitor had no effect. Using protease inhibitors to prevent the cleavage of surface-bound IgG increased the binding of complement C3 fragments on the surface of S. aureus, increased the association with human neutrophils and increased phagocytosis by human neutrophils. PMID:21636671

  15. Sialylation of IgG Fc domain impairs complement-dependent cytotoxicity.

    PubMed

    Quast, Isaak; Keller, Christian W; Maurer, Michael A; Giddens, John P; Tackenberg, Björn; Wang, Lai-Xi; Münz, Christian; Nimmerjahn, Falk; Dalakas, Marinos C; Lünemann, Jan D

    2015-11-01

    IgG molecules exert both pro- and antiinflammatory effector functions based on the composition of the fragment crystallizable (Fc) domain glycan. Sialylated IgG Fc domains have antiinflammatory properties that are attributed to their ability to increase the activation threshold of innate effector cells to immune complexes by stimulating the upregulation of the inhibitory Fcγ receptor IIB (FcγRIIB). Here, we report that IgG Fc sialylation of human monoclonal IgG1 molecules impairs their efficacy to induce complement-mediated cytotoxicity (CDC). Fc sialylation of a CD20-targeting antibody had no impact on antibody-dependent cellular cytotoxicity and did not change the affinity of the antibody for activating Fcγ receptors. In contrast, the presence of sialic acid abrogated the increased binding of C1q to Fc-galactosylated IgG1 and resulted in decreased levels of C3b deposition on the cell surface. Similar to monoclonal antibodies, sialic acid inhibited the increased C1q binding to galactosylated Fc fragments in human polyclonal IgG. In sera derived from patients with chronic inflammatory demyelinating polyneuropathy, an autoimmune disease of the peripheral nervous system in which humoral immune responses mediate tissue damage, induction of IgG Fc sialylation was associated with clinical disease remission. Thus, impairment of CDC represents an FcγR-independent mechanism by which Fc-sialylated glycovariants might limit proinflammatory IgG effector functions. PMID:26436649

  16. Sialylation of IgG Fc domain impairs complement-dependent cytotoxicity

    PubMed Central

    Quast, Isaak; Keller, Christian W.; Maurer, Michael A.; Giddens, John P.; Tackenberg, Björn; Wang, Lai-Xi; Münz, Christian; Nimmerjahn, Falk; Dalakas, Marinos C.; Lünemann, Jan D.

    2015-01-01

    IgG molecules exert both pro- and antiinflammatory effector functions based on the composition of the fragment crystallizable (Fc) domain glycan. Sialylated IgG Fc domains have antiinflammatory properties that are attributed to their ability to increase the activation threshold of innate effector cells to immune complexes by stimulating the upregulation of the inhibitory Fcγ receptor IIB (FcγRIIB). Here, we report that IgG Fc sialylation of human monoclonal IgG1 molecules impairs their efficacy to induce complement-mediated cytotoxicity (CDC). Fc sialylation of a CD20-targeting antibody had no impact on antibody-dependent cellular cytotoxicity and did not change the affinity of the antibody for activating Fcγ receptors. In contrast, the presence of sialic acid abrogated the increased binding of C1q to Fc-galactosylated IgG1 and resulted in decreased levels of C3b deposition on the cell surface. Similar to monoclonal antibodies, sialic acid inhibited the increased C1q binding to galactosylated Fc fragments in human polyclonal IgG. In sera derived from patients with chronic inflammatory demyelinating polyneuropathy, an autoimmune disease of the peripheral nervous system in which humoral immune responses mediate tissue damage, induction of IgG Fc sialylation was associated with clinical disease remission. Thus, impairment of CDC represents an FcγR-independent mechanism by which Fc-sialylated glycovariants might limit proinflammatory IgG effector functions. PMID:26436649

  17. Co-existing ligneous conjunctivitis and IgG4-related disease.

    PubMed

    Chiang, Wei-Yu; Liu, Ting-Ting; Huang, Wan-Ting; Kuo, Ming-Tse

    2016-07-01

    Herein, we elucidate that ligneous conjunctivitis (LC) was proved as an IgG4-related disease (IgG4-RD) by a series of pathologic studies from primary and recurrent episodes of an LC patient. LC was diagnosed based on clinical presentation and pathological appearance; furthermore, combined with serological examination and immunohistochemical study, the case also conformed to the diagnosis of IgG4-RD. The IgG4-RD, broadly discussed in recent times, is an idiopathic disease entity with tissue fibrosis possibly involving multiple organs. To the best of our knowledge, IgG4-RD has never been reported with LC. By reporting the clinical course and literature review, we should pay attention to the association between these two diseases. PMID:27609168

  18. A case of refractory IgG4-related peripheral neuropathy with severe axonal damage.

    PubMed

    Suzuki, Yu; Shiraishi, Makoto; Yamada, Koji; Doi, Masatomo; Kato, Masayuki; Hasegawa, Yasuhiro

    2016-05-31

    A 78-year-old man presented complaining of tingling and pain. Neurological examination revealed dysesthesia and hypothermesthesia below both knees and areflexia in the lower extremities. Laboratory data revealed elevated serum levels of immunoglobulin IgG4 and para-aortic, and mesenteric lymphadenopathy was evident on plain computed tomography of the abdomen. Microscopic findings of a bone marrow biopsy specimen showed occlusion of blood vessels with IgG4-positive plasma cells. IgG4-related disease was diagnosed because the bone marrow biopsy exhibited > 10 IgG4-positive plasma cells per high-power field. Treatment was initiated with prednisolone starting at 30 mg/day, but no improvement in neurological symptoms was achieved. Sural nerve biopsy demonstrated obstructive thromboangiitis with severe loss of myelin and axons. Further investigations are needed to elucidate the relationship between obstructive thromboangiitis and steroid-resistant IgG4-related peripheral neuropathy. PMID:27098901

  19. Low avidity IgG antibodies in diagnosis of recent human schistosomiasis.

    PubMed

    Mostafa, Nahed E; Awad, Adel; Shalaby, Mohsen

    2002-12-01

    One hundred thirty school children from a schistosomiasis endemic area in Sharkia Governorate, were selected on parasitological findings. Seventy persons were negative on the first screen and turned positive after 3 months of the screening (recently infected). Stool examination, ELISA (IgG & IgM), low avid IgG, and circulating antigens were performed for all patients and controls. ELISA detected IgM in all cases. IgG and circulating antigens in 90% of schistosomiasis patients. Low avidity IgG were detected in 85.71% of recent cases. The specificity of ELISA appeared to be >99%. The IgM/IgG ratio was >1 in patients with recent infection. The percentage of fall of O.D. readings of IgG after addition of 6 molar urea was high among cases with recent infection. Low avid lgG appears to be good and valuable in diagnosis of recent schistosomiasis in man. PMID:12512829

  20. Sialylation converts arthritogenic IgG into inhibitors of collagen-induced arthritis.

    PubMed

    Ohmi, Yuhsuke; Ise, Wataru; Harazono, Akira; Takakura, Daisuke; Fukuyama, Hidehiro; Baba, Yoshihiro; Narazaki, Masashi; Shoda, Hirofumi; Takahashi, Nobunori; Ohkawa, Yuki; Ji, Shuting; Sugiyama, Fumihiro; Fujio, Keishi; Kumanogoh, Atsushi; Yamamoto, Kazuhiko; Kawasaki, Nana; Kurosaki, Tomohiro; Takahashi, Yoshimasa; Furukawa, Koichi

    2016-01-01

    Rheumatoid arthritis (RA)-associated IgG antibodies such as anti-citrullinated protein antibodies (ACPAs) have diverse glycosylation variants; however, key sugar chains modulating the arthritogenic activity of IgG remain to be clarified. Here, we show that reduced sialylation is a common feature of RA-associated IgG in humans and in mouse models of arthritis. Genetically blocking sialylation in activated B cells results in exacerbation of joint inflammation in a collagen-induced arthritis (CIA) model. On the other hand, artificial sialylation of anti-type II collagen antibodies, including ACPAs, not only attenuates arthritogenic activity, but also suppresses the development of CIA in the antibody-infused mice, whereas sialylation of other IgG does not prevent CIA. Thus, our data demonstrate that sialylation levels control the arthritogenicity of RA-associated IgG, presenting a potential target for antigen-specific immunotherapy. PMID:27046227

  1. Characteristics, diagnosis and therapeutic strategies for IgG4-related orbital disease.

    PubMed

    Oles, Krzysztof; Sładzień, Jacek; Bartuś, Krzysztof; Leszczyńska, Joanna; Bojanowska, Emila; Krakowczyk, Łukasz; Mika, Joanna

    2016-06-01

    Thanks to detailed studies conducted in recent years, a new disease syndrome was identified in 2001. It is known as a IgG4-related disease and its differentiation is based on the analysis of IgG4 levels in the affected tissues. The IgG4-related disease is considered to be a generalized pathological process involving a wide spectrum of various disorders that may affect distant organs. Orbital IgG4-related disease is a recently reported issue that may prove important for the elucidation of the etiology of idiopathic, lymphoplasmacytic or fibrotic disorders of various organs, including the orbits. In this article, we are describing epidemiology and differential diagnostics of IgG4-related orbital disease with particular focus on pseudotumors, MALT lymphomas and lymphocyte/plasma cell infiltrations of the orbit. We are also discussing therapeutic possibilities currently available in the management of the disease. PMID:27116895

  2. Alum Directly Modulates Murine B Lymphocytes to Produce IgG1 Isotype

    PubMed Central

    Jin, Bo-Ra; Kim, Sun-Jin; Lee, Jeong-Min; Kang, Seong-Ho; Han, Hye-Ju; Jang, Young-Saeng; Seo, Goo-young

    2013-01-01

    Aluminum hydroxide (alum) is the most widely used adjuvant in human vaccines. Nevertheless, it is virtually unknown whether alum acts on B cells. In the present study, we explored the direct effect of alum on Ig expression by murine B cells in vitro. LPS-activated mouse spleen B cells were cultured with alum, and the level of isotype-specific Ig secretion, IgG1 secreting cell numbers, and Ig germ-line transcripts (GLT) were measured using ELISA, ELISPOT, and RT-PCR, respectively. Alum consistently enhanced total IgG1 production, numbers of IgG1 secreting cells, and GLTγ1 expression. These results demonstrate that alum can directly cause IgG1 isotype switching leading to IgG1 production. PMID:23559895

  3. Sialylation converts arthritogenic IgG into inhibitors of collagen-induced arthritis

    PubMed Central

    Ohmi, Yuhsuke; Ise, Wataru; Harazono, Akira; Takakura, Daisuke; Fukuyama, Hidehiro; Baba, Yoshihiro; Narazaki, Masashi; Shoda, Hirofumi; Takahashi, Nobunori; Ohkawa, Yuki; Ji, Shuting; Sugiyama, Fumihiro; Fujio, Keishi; Kumanogoh, Atsushi; Yamamoto, Kazuhiko; Kawasaki, Nana; Kurosaki, Tomohiro; Takahashi, Yoshimasa; Furukawa, Koichi

    2016-01-01

    Rheumatoid arthritis (RA)-associated IgG antibodies such as anti-citrullinated protein antibodies (ACPAs) have diverse glycosylation variants; however, key sugar chains modulating the arthritogenic activity of IgG remain to be clarified. Here, we show that reduced sialylation is a common feature of RA-associated IgG in humans and in mouse models of arthritis. Genetically blocking sialylation in activated B cells results in exacerbation of joint inflammation in a collagen-induced arthritis (CIA) model. On the other hand, artificial sialylation of anti-type II collagen antibodies, including ACPAs, not only attenuates arthritogenic activity, but also suppresses the development of CIA in the antibody-infused mice, whereas sialylation of other IgG does not prevent CIA. Thus, our data demonstrate that sialylation levels control the arthritogenicity of RA-associated IgG, presenting a potential target for antigen-specific immunotherapy. PMID:27046227

  4. The Effect of Maternal Helminth Infection on Maternal and Neonatal Immune Function and Immunity to Tuberculosis

    PubMed Central

    Gebreegziabiher, Dawit; Desta, Kassu; Desalegn, Girmay; Howe, Rawleigh; Abebe, Markos

    2014-01-01

    Background M. tuberculosis and helminth infection each affects one third of the world population. Helminth infections down regulate cell mediated immune responses and this may contribute to lower efficacy of BCG vaccination and higher prevalence of tuberculosis. Objective To determine the effect of maternal helminth infection on maternal and neonatal immune function and immunity to TB. Methods In this cross sectional study, eighty five pregnant women were screened for parasitic and latent TB infections using Kato-Katz and QFT-GIT tests, respectively. IFN-γ and IL-4 ELISpot on Cord blood Mononuclear Cells, and total IgE and TB specific IgG ELISA on cord blood plasma was performed to investigate the possible effect of maternal helminth and/or latent TB co-infection on maternal and neonatal immune function and immunity to TB. Result The prevalence of helminth infections in pregnant women was 27% (n = 23), with Schistosoma mansoni the most common helminth species observed (20% of women were infected). Among the total of 85 study participants 25.8% were QFT-GIT positive and 17% had an indeterminate result. The mean total IgE value of cord blood was significantly higher in helminth positive than negative women (0.76 vs 0.47, p = 0.042). Cross placental transfer of TB specific IgG was significantly higher in helminth positive (21.9±7.9) than negative (12.3±5.1), p = 0.002) Latent TB Infection positive participants. The IFN-γ response of CBMCs to ESAT-6/CFP-10 cocktail (50 vs 116, p = 0.018) and PPD (58 vs 123, p = 0.02) was significantly lower in helminth positive than negative participants. There was no significant difference in IL-4 response of CBMCs between helminth negative and positive participants. Conclusions Maternal helminth infection had a significant association with the IFN-γ response of CBMCs, total IgE and cross placental transfer of TB specific IgG. Therefore, further studies should be conducted to determine the effect of these

  5. Refractometer assessment of colostral and serum IgG and milk total solids concentrations in dairy cattle

    PubMed Central

    2014-01-01

    Background Estimation of the quantity of colostral IgG or serum IgG absorbed following ingestion of colostrum by calves is essential for monitoring the effectiveness of colostrum feeding practices on dairy farms. Milk total solids concentrations determination is a critical part of quality assessment of nonsaleable whole milk prior to feeding to calves. To date, on-farm methods to assess colostral IgG, serum IgG or milk total solids concentrations have been performed separately with various instruments. The objective of this study was to evaluate the diagnostic performance of a single electronic, hand-held refractometer for assessing colostral and serum IgG concentrations and milk total solids in dairy cattle. Colostral IgG, serum IgG and milk total solids concentrations were determined by the refractometer. Corresponding analysis of colostral and serum IgG concentrations were determined by radial immunodiffusion (RID) while milk total solids were determined by spectrophotometry. Sensitivity and specificity of the refractometer for colostrum and serum samples were calculated as determined by RID. Sensitivity and specificity of the refractometer for milk samples was calculated as determined by spectrophotometry. Results The sensitivity of the refractometer was 1 for colostral IgG, serum IgG and milk total solids determinations. Specificity of the refractometer was 0.66, 0.24 and 0 for colostral IgG, serum IgG and milk total solids determinations, respectively. The refractometer underestimated colostral IgG, serum IgG and milk total solids concentrations compared to the concentrations determined by RID or spectrophotometry. Conclusions The refractometer was an acceptable, rapid, convenient on-farm method for determining colostral IgG and milk total solids. The refractometer was not an acceptable method for determination of serum IgG concentrations as it severely underestimated the serum IgG concentrations. PMID:25125217

  6. Protective role of mouse IgG1 in cryoglobulinaemia; insights from an animal model and relevance to human pathology.

    PubMed

    Chemouny, Jonathan Maurice; Hurtado-Nedelec, Margarita; Flament, Héloïse; Ben Mkaddem, Sanae; Daugas, Eric; Vrtovsnik, François; Berthelot, Laureline; Monteiro, Renato C

    2016-08-01

    Strait et al. described a novel mouse model of cryoglobulinaemia by challenging mice deficient in the immunoglobulin (Ig)G1 subclass (γ1(-) mice) with goat anti-mouse IgD [5]. The phenotype of wild-type mice was not remarkable, whereas γ1(-) mice developed IgG3 anti-goat IgG cryoglobulins as well as severe and lethal glomerulonephritis. Renal phenotype could not be rescued in γ1(-) mice by the deletion of C3, fragment crystalline γ receptor (FcγR) or J chain. On the other hand, early injection of IgG1, IgG2a or IgG2b inhibited the pathogenic effects of IgG3 in an antigen-dependent manner even in the absence of the FcγRIIb, an anti-inflammatory receptor. The authors concluded that the pathogenic role of IgG3 and the protective characteristic of IgG1 in this model were not explained by their abilities to bind to FcRs or effector molecules but are rather due to structural discrepancies enhancing the precipitation properties/solubility of IgG3/IgG1-containing immune complexes. The present article aims to discuss the current knowledge on IgG biology and the properties of IgGs explaining their differential propensity to acquire cryoglobulin activity. PMID:26410885

  7. Passive immunization with allergen-specific IgG antibodies for treatment and prevention of allergy

    PubMed Central

    Flicker, Sabine; Linhart, Birgit; Wild, Carmen; Wiedermann, Ursula; Valenta, Rudolf

    2013-01-01

    IgE antibody-mediated allergies affect more than 25% of the population worldwide. To investigate therapeutic and preventive effects of passive immunization with allergen-specific IgG antibodies on allergy in mouse models we used clinically relevant pollen allergens. In a treatment model, mice were sensitized to the major birch pollen allergen Bet v 1 and to the major grass pollen allergens, Phl p 1 and Phl p 5 and then received passive immunization with rabbit IgG antibodies specific for the sensitizing or an unrelated allergen. In a prevention model, mice obtained passive immunization with allergen-specific rabbit IgG before sensitization. Kinetics of the levels of administered IgG antibodies, effects of administered allergen-specific IgG on allergen-specific IgE reactivity, the development of IgE and IgG responses and on immediate allergic reactions were studied by ELISA, rat basophil leukaemia degranulation assays and skin testing, respectively. Treated mice showed an approximately 80% reduction of allergen-specific IgE binding and basophil degranulation which was associated with the levels of administered allergen-specific IgG antibodies. Preventive administration of allergen-specific IgG antibodies suppressed the development of allergen-specific IgE and IgG1 antibody responses as well as allergen-induced basophil degranulation and skin reactivity. Our results show that passive immunization with allergen-specific IgG antibodies is effective for treatment and prevention of allergy to clinically important pollen allergens in a mouse model and thus may pave the road for the clinical application of allergen-specific antibodies in humans. PMID:23182706

  8. IgG4-related Hashimoto's thyroiditis--a new variant of a well known disease.

    PubMed

    Luiz, Henrique Vara; Gonçalves, Diogo; Silva, Tiago Nunes da; Nascimento, Isabel; Ribeiro, Ana; Mafra, Manuela; Manita, Isabel; Portugal, Jorge

    2014-11-01

    Hashimoto's thyroiditis (HT) has been characterized for many years as a well-defined clinicopathologic entity, but is now considered a heterogeneous disease. IgG4-related HT is a new subtype characterized by thyroid inflammation rich in IgG4-positive plasma cells and marked fibrosis. It may be part of the systemic IgG4-related disease. We report a case of a 56-year-old Portuguese man who presented with a one-month history of progressive neck swelling and dysphagia. Laboratory testing revealed increased inflammatory parameters, subclinical hypothyroidism and very high levels of thyroid autoantibodies. Cervical ultrasound (US) demonstrated an enlarged and heterogeneous thyroid gland and two hypoechoic nodules. US-guided fine needle aspiration cytology was consistent with lymphocytic thyroiditis. The patient was submitted to total thyroidectomy and microscopic examination identified typical findings of HT, marked fibrosis limited within the thyroid capsule and lymphoplasmacytic infiltration, with >50 IgG4-positive plasma cells per high-power field and an IgG4/IgG ratio of >40%. After surgery, serum IgG4 concentration was high-normal. Symptoms relief and reduction in laboratory inflammatory parameters were noticed. Thyroid function is controlled with levothyroxine. To our knowledge we report the first case of IgG4-related HT in a non-Asian patient. We also perform a review of the literature regarding IgG4-related disease and IgG4-related HT. Our case highlights this new variant of the well known HT, and helps physicians in recognizing its main clinical features, allowing for proper diagnosis and treatment. PMID:25465611

  9. Protection against neonatal Escherichia coli diarrhea by vaccination of sows with a novel multivalent vaccine candidate expressing E. coli adhesins associated with neonatal pig colibacillosis.

    PubMed

    Hur, Jin; Lee, John Hwa

    2013-04-01

    In this study, we investigated the optimal condition of a novel multivalent Escherichia coli vaccine candidate for protection efficacy against E. coli colibacillosis in piglets via booster strategy using oral and intramuscular administration routes. The candidate was constructed using an expression and secretion plasmid and an attenuated Salmonella delivery system as described earlier. Pregnant sows were divided into four groups of three sows each and immunized with a mixture of the individual vaccine strains. Sows were primed and boosted at 8 and 11 weeks of pregnancy. Group A sows were primed intramuscularly and boosted orally. Group B sows were primed and boosted orally. Group C sows were orally primed and intramuscularly boosted. Group D sows were primed and boosted with PBS as a control. The serum IgG and IgA levels to individual adhesin antigens were elevated in immunized sows compared to controls, as were colostral IgA and IgG levels of all immunized sows. In addition, serum IgG and IgA levels in piglets from all immunized sows were significantly increased. These data suggest that systemic and colostral immune responses were highly induced by vaccination with the candidate. After challenge with a virulent strain of E. coli, clinical signs such as diarrhea and mortality were not observed in suckling piglets from the immunized sows, while diarrhea and mortality affected 100% and 25% of the control group piglets, respectively. These findings indicate that immunization of sows with the candidate vaccine irrespective of administration routes can effectively protect their piglets against neonatal E. coli diarrhea. PMID:22959394

  10. Neonatal aerosol exposure to Bermuda grass allergen prevents subsequent induction of experimental allergic feline asthma: evidence for establishing early immunologic tolerance.

    PubMed

    Heller, M C; Lee-Fowler, T M; Liu, H; Cohn, L A; Reinero, C R

    2014-07-15

    Allergic asthma is increasing in industrialized countries, especially in children. Rodent and human studies suggest an opportunity to "prevent" asthma in the perinatal period. The aims of this study were to create a more "natural" model of feline asthma by exposing offspring of asthmatic queens to Bermuda grass allergen (BGA) by inhalation only, and to investigate maternal-fetal-infant interactions in the development of asthma. Kittens from asthmatic queens were divided into four groups: maternal exposure to aerosolized BGA during the third trimester, neonatal exposure to aerosolized BGA in the first three months of life, both maternal and neonatal exposure, or saline control. Kittens failing to achieve an asthmatic phenotype based on bronchoalveolar lavage fluid (BALF) analysis by 6 months underwent traditional sensitization: adjuvanted allergen injection, intranasal allergen, and aerosol challenges. BALF was collected at 3, 4 and 6 months, and after sensitization at 8 months, and analyzed for eosinophil counts and BGA-specific IgG and IgA. Intradermal testing (IDT) was performed at 6 and 7 months. At six months none of the kittens had airway eosinophilia, BGA-specific IgG or IgA, and were non-responsive to IDT. After sensitization, kittens receiving neonatal aerosolization failed to develop airway eosinophilia as seen in the controls. Kittens exposed to BGA aerosols, either in-utero or neonatally, continued to lack IDT response. Chronic exposure to BGA aerosols failed to induce asthma in kittens, and instead tolerized the kittens to BGA. This is the first evidence that neonatal intervention could potentially "prevent" allergic asthma in cats. PMID:24704287

  11. Serum Concentrations of IgG4 in the Spanish Adult Population: Relationship with Age, Gender, and Atopy

    PubMed Central

    Carballo, Iago; Alvela, Lucía; Pérez, Luis-Fernando; Gude, Francisco; Vidal, Carmen; Alonso, Manuela; Sopeña, Bernardo; Gonzalez-Quintela, Arturo

    2016-01-01

    Background and Aim Serum IgG4 concentrations are commonly measured in clinical practice. The aim of this study was to investigate serum IgG4 concentrations in adults and their potential relationship with demographic, lifestyle, metabolic, and allergy-related factors. Methods Serum IgG4 concentrations were measured with a commercial assay in 413 individuals (median age 55 years, 45% males) who were randomly selected from a general adult population. Results Median IgG4 concentration was 26.8 mg/dL. Five out of the 413 individuals (1.2%) exhibited IgG4 concentrations >135 mg/dL, and 17 out of 411 (4.1%) exhibited an IgG4/total IgG ratio >8%. Serum IgG4 concentrations were significantly higher in males than in females and decreased with age. After adjusting for age and sex, serum IgG4 concentrations were not significantly influenced by alcohol consumption, smoking or common metabolic abnormalities (obesity and the related metabolic syndrome). Serum IgG4 concentrations were not significantly correlated with serum concentrations of proinflammatory cytokines and inflammation markers. Serum IgG4 concentrations were significantly correlated with IgE concentrations. Serum IgG4 concentrations tended to be higher in atopics (individuals with IgE-mediated sensitization to aeroallergens) than in non-atopics, particularly among atopics without respiratory symptoms. Serum IgG4 concentrations were not significantly correlated with total eosinophil blood count. Cases of IgG4-related disease were neither present at baseline nor detected after a median of 11 years of follow-up. Conclusions Studies aimed at defining reference IgG4 values should consider partitioning by age and sex. Further studies are needed to confirm the potential influence of atopy status on serum IgG4 concentrations. PMID:26910567

  12. Intravenous IgG (IVIG) and subcutaneous IgG (SCIG) preparations have comparable inhibitory effect on T cell activation, which is not dependent on IgG sialylation, monocytes or B cells.

    PubMed

    Issekutz, Andrew C; Rowter, Derek; Miescher, Sylvia; Käsermann, Fabian

    2015-10-01

    IVIG modulates T cell activation in vitro and inflammatory-autoimmune conditions in vivo. Sialylation of IgG, Fc receptor interactions, modulation of monocyte/macrophage/B cell functions have been implicated in IVIG effects. Subcutaneous IgG (SCIG) therapy is increasingly used for IgG replacement but whether these preparations share the effects of IVIG on T cell modulation is not documented. We compared the potency of SCIG-Hizentra™ (20% IgG preparation) with IVIG-Privigen® (10% IgG) for T cell inhibition, and assessed the involvement of IgG sialylation, monocytes and B cells in this process. Human PBMCs or sorted cells were cultured 3-7 days, and T cells were stimulated with immobilized anti-CD3 mAb or Candida antigen. Thymidine incorporation into DNA was quantitated and cytokines assayed by ELISA/Luminex® assay. IVIG and SCIG both dose-dependently (1-20mg/ml) inhibited (up to >80%) T cell proliferation to anti-CD3 mAb. Response to Candida albicans was comparably inhibited by IVIG and SCIG by 50-80% at 10mg/ml with inhibition even at 3mg/ml (P<0.05). These effects were not affected by depletion of sialic acid containing IgG using neuraminidase treatment or lectin affinity chromatography. With anti-CD3 or Candida stimulation, IL-1β, IL-2, IL-5, IL-6, IL-13, GMCSF, TNF-α, interferon-γ (with anti-CD3) and IL-17 (with Candida) levels were suppressed by IVIG or SCIG, with no effect on IL-4, IL-10, IL-12, IL-15 or TGFβ. Monocytes or B cells were not required for IgG-induced suppression of proliferation, in fact depletion of monocytes potentiated the IgG-induced inhibition. Reconstitution with monocytes restored the original inhibitory effect. These data show that IVIG (Privigen®) and SCIG (Hizentra™) have comparable inhibitory effects on T cell activation, which do not require sialylation of IgG. Inhibition is independent of monocytes or B cells. There is a potent suppression of multiple effector cytokines. Like IVIG, SCIG therapy is expected to show

  13. Maternal and Neonatal Care. Teacher Edition.

    ERIC Educational Resources Information Center

    Oklahoma State Dept. of Vocational and Technical Education, Stillwater. Curriculum and Instructional Materials Center.

    This curriculum guide contains the materials required to teach a course in maternal and neonatal care that will prepare students for employment as practical nurses. The course's five instructional units cover procedures for caring for the following: prenatal patients, patients in labor and delivery, postpartum patients, healthy neonates, and…

  14. Teamwork in the Neonatal Intensive Care Unit

    ERIC Educational Resources Information Center

    Barbosa, Vanessa Maziero

    2013-01-01

    Medical and technological advances in neonatology have prompted the initiation and expansion of developmentally supportive services for newborns and have incorporated rehabilitation professionals into the neonatal intensive care unit (NICU) multidisciplinary team. Availability of therapists specialized in the care of neonates, the roles of…

  15. Rural Hospital Preparedness for Neonatal Resuscitation

    ERIC Educational Resources Information Center

    Jukkala, Angela; Henly, Susan J.; Lindeke, Linda

    2008-01-01

    Context: Neonatal resuscitation is a critical component of perinatal services in all settings. Purpose: To systematically describe preparedness of rural hospitals for neonatal resuscitation, and to determine whether delivery volume and level of perinatal care were associated with overall preparedness or its indicators. Methods: We developed the…

  16. Neonate with hypoglycemia for pancreatectomy: Anesthetic challenge

    PubMed Central

    Gupta, Alka; Kohli, Jasvinder Kaur; Senapati, Nihar Nalini; Sharma, Sanjeev

    2016-01-01

    Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is rare and an important cause of hypoglycemia in neonates. It can lead to brain damage or death secondary to severe hypoglycemia. We present the anesthetic management in a diagnosed case of PHHI in an 8-day-old male neonate for total pancreatectomy. PMID:26957713

  17. Mechanisms of Neonatal Mucosal Antibody Protection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Following an abrupt transition at birth from the sterile uterus to an environment with abundant commensal and pathogenic microbes, neonatal mammals are protected by maternal antibodies at mucosal surfaces. We show in mice that different antibody isotypes work in distinct ways to protect the neonatal...

  18. Brazelton Neonatal Assessment for School Psychologists.

    ERIC Educational Resources Information Center

    Stoudt, Calvin L.

    This speech addresses the "What,""Why," and "How" of Brazelton Neonatal Assessment Training for school psychologists. "What" concerns the Brazelton Neonatal Behavioral Assessment Scale, its administration, and what it assesses. Based on the best performance, the infant's score on this scale is scored in the context of six states of consciousness…

  19. Neonatal Seizures: Impact on Neurodevelopmental Outcomes

    PubMed Central

    Kang, Seok Kyu; Kadam, Shilpa D.

    2015-01-01

    Neonatal period is the most vulnerable time for the occurrence of seizures, and neonatal seizures often pose a clinical challenge both for their acute management and frequency of associated long-term co-morbidities. Etiologies of neonatal seizures are known to play a primary role in the anti-epileptic drug responsiveness and the long-term sequelae. Recent studies have suggested that burden of acute recurrent seizures in neonates may also impact chronic outcomes independent of the etiology. However, not many studies, either clinical or pre-clinical, have addressed the long-term outcomes of neonatal seizures in an etiology-specific manner. In this review, we briefly review the available clinical and pre-clinical research for long-term outcomes following neonatal seizures. As the most frequent cause of acquired neonatal seizures, we focus on the studies evaluating long-term effects of HIE-seizures with the goal to evaluate (1) what parameters evaluated during acute stages of neonatal seizures can reliably be used to predict long-term outcomes? and (2) what available clinical and pre-clinical data are available help determine importance of etiology vs. seizure burdens in long-term sequelae. PMID:26636052

  20. Acute neonatal appendicitis in a preterm.

    PubMed

    Mammou, Sihem; Ayadi, Imen; Ben Hamida, Emira; Marrakchi, Zahra

    2015-01-01

    Acute neonatal appendicitis is very rare in the neonatal period. It is usually associated with comorbidity including prematurity. Symptoms are non-specific. The prognosis is marked by high risk of mortality and morbidity. Here, we report a case of preterm new born who presented with sepsis, apnoea, and digestive signs. The laparotomy revealed perforated appendicitis complicated with peritonitis. PMID:26712299

  1. Murine neonatal intravascular injections: Modeling newborn disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The ability to perform murine neonatal intravascular injections likely will prove useful in studying many newborn-specific disease states that are modeled in mice. Unfortunately, effective intravascular injection in the neonatal mouse has been limited by developmental immaturity and small size. To e...

  2. Acute neonatal appendicitis in a preterm

    PubMed Central

    Mammou, Sihem; Ayadi, Imen; Hamida, Emira Ben; Marrakchi, Zahra

    2015-01-01

    Acute neonatal appendicitis is very rare in the neonatal period. It is usually associated with comorbidity including prematurity. Symptoms are non-specific. The prognosis is marked by high risk of mortality and morbidity. Here, we report a case of preterm new born who presented with sepsis, apnoea, and digestive signs. The laparotomy revealed perforated appendicitis complicated with peritonitis. PMID:26712299

  3. Foetal and neonatal alloimmune thrombocytopaenia

    PubMed Central

    Kaplan, Cecile

    2006-01-01

    Foetal/neonatal alloimmune thrombocytopaenia (NAIT) results from maternal alloimmunisation against foetal platelet antigens inherited from the father and different from those present in the mother, and usually presents as a severe isolated thrombocytopaenia in otherwise healthy newborns. The incidence has been estimated at 1/800 to 1/1 000 live births. NAIT has been considered to be the platelet counterpart of Rh Haemolytic Disease of the Newborn (RHD). Unlike RHD, NAIT can occur during a first pregnancy. The spectrum of the disease may range from sub-clinical moderate thrombocytopaenia to life-threatening bleeding in the neonatal period. Mildly affected infants may be asymptomatic. In those with severe thrombocytopaenia, the most common presentations are petechiae, purpura or cephalohaematoma at birth, associated with major risk of intracranial haemorrhage (up to 20% of reported cases), which leads to death or neurological sequelae. Alloimmune thrombocytopaenia is more often unexpected and is usually diagnosed after birth. Once suspected, the diagnosis is confirmed by demonstration of maternal antiplatelet alloantibodies directed against a paternal antigen inherited by the foetus/neonate. Post-natal management involves transfusion of platelets devoid of this antigen, and should not be delayed by biological confirmation of the diagnosis (once the diagnosis is suspected), especially in case of severe thrombocytopaenia. Prompt diagnosis and treatment are essential to reduce the chances of death and disability due to haemorrhage. Due to the high rate of recurrence and increased severity of the foetal thrombocytopaenia in successive pregnancies, antenatal therapy should be offered. However, management of high-risk pregnancies is still a matter of discussion. PMID:17032445

  4. [Neonatal intermittent hypoxia and hypertension].

    PubMed

    Sukhova, G K; Nozdrachev, A D; Gozal, D

    2009-01-01

    Obstructive apnea during sleep is accompanied by intermittent hypoxia (IH) leading to hypertension and other cardiovascular disturbances. A comparative evaluation of long-term effects of the neonatal IH on the cardiovascular function was performed in normotensive Sprague-Dawley and spontaneously hypertensive rats (SHR). The newborn rats were placed for 30 days to conditions of IH (8 and 21% O2, alternating every 90 s for 12 h/day). Control groups of rats were constantly kept in normoxia. By 6 months, in the spontaneously hypertensive rats submitted to IH at the period of wakefulness there was a statistically significant increase (as compared with control) of the systolic (correspondingly 185.8 +/- 1.7 and 169.9 +/- 1.4 mm Hg, p < 0.01) and diastolic pressure (correspondingly 96.2 +/- 4.9 and 86.0 +/- 2.6 mm Hg, p < 0.01). During sleep, the systolic and diastolic pressure in these rats was higher than in control animals by 10 mm Hg (p < 0.01) and 12 mm Hg (p < 0.01), its decrease during sleep being absent. SHR submitted to IH had an increase in low- to the high-frequency power ratio of the heart rate variability from 0.9 +/- 0.15 to 1.5 +/- 0.17, which indicates a shift of the sympatho-parasympathetic balance in this group towards predominance of the sympathetic component. In the Sprague-Dawley rats submitted to neonatal hypoxia, the above changes were not pronounced. These peculiarities of the hypertensive rats allow establishing connection of the genetic factor with the sympathetic mechanism providing long-term consequences of the neonatal IH for the cardiovascular control in these rats. PMID:19435263

  5. Igg Subclasses Targeting the Flagella of Salmonella enterica Serovar Typhimurium Can Mediate Phagocytosis and Bacterial Killing

    PubMed Central

    Goh, Yun Shan; Armour, Kathryn L; Clark, Michael R; Grant, Andrew J; Mastroeni, Pietro

    2016-01-01

    Invasive non-typhoidal Salmonella are a common cause of invasive disease in immuno-compromised individuals and in children. Multi-drug resistance poses challenges to disease control, with a critical need for effective vaccines. Flagellin is an attractive vaccine candidate due to surface exposure and high epitope copy number, but its potential as a target for opsonophacytic antibodies is unclear. We examined the effect of targeting flagella with different classes of IgG on the interaction between Salmonella Typhimurium and a human phagocyte-like cell line, THP-1. We tagged the FliC flagellar protein with a foreign CD52 mimotope (TSSPSAD) and bacteria were opsonized with a panel of humanised CD52 antibodies with the same antigen-binding V-region, but different constant regions. We found that IgG binding to flagella increases bacterial phagocytosis and reduces viable intracellular bacterial numbers. Opsonisation with IgG3, followed by IgG1, IgG4, and IgG2, resulted in the highest level of bacterial uptake and in the highest reduction in the intracellular load of viable bacteria. Taken together, our data provide proof-of-principle evidence that targeting flagella with antibodies can increase the antibacterial function of host cells, with IgG3 being the most potent subclass. These data will assist the rational design of urgently needed, optimised vaccines against iNTS disease. PMID:27366588

  6. Induction of IgG in young nude mice by lipid A or thymus grafts.

    PubMed

    Kolb, C; Di Pauli, R; Weiler, E

    1976-10-01

    Postnatal serum concentrations of IgG2a of paternal allotype, measured in congenitally thymusless nude mice, increase with kinetics and titers comparable to their normal congeneic counterparts. Lipid A, the mitogenic part of LPS, stimulates IgG synthesis in nude mice when it is given 7 days after birth. IgG concentrations at 15 days of age are 6- to 8-fold higher than in untreated control nudes; this is considerably lower, however, than in normal mice, which show up to 45-fold higher IgG2ab levels after lipid A treatment. A thymus graft from nearly congeneic donors of the same age, transplanted at 4 days after birth, also stimulates long-lasting IgG synthesis in the nude recipients. If the grafted nudes are injected with lipid A 3 days later, IgG synthesis is further stimulated 8- to 16-fold. The data are discussed in relation to the thymus dependency of IgG production and the conditions for lipid A stimulation. PMID:978133

  7. Extraction and purification of active IgG from SSPE and MS brain.

    PubMed

    Owens, G P; Burgoon, M P; Devlin, M E; Gilden, D H

    1997-11-01

    Immunoglobulin (Ig) G was purified from soluble and membrane fractions of postmortem subacute sclerosing panencephalitis (SSPE) brain, multiple sclerosis (MS) brain plaque-periplaque white matter, and normal human brain (NHB) white matter. After homogenization in 0.32 M sucrose and removal of cell debris and nuclei by low-speed centrifugation, soluble and crude membrane fractions were separated by ultracentrifugation. After removal of sucrose by dialysis, IgG was isolated from the soluble fraction by protein A affinity chromatography. IgG was obtained from the membrane fraction by elution at low pH and purification from the eluate by protein A chromatography. Whereas very little IgG was in NHB white matter, significant levels of IgG were recovered from both SSPE and MS brain. Both immunocytochemical staining of measles virus-infected cells in tissue culture and protein immunoblotting of virus-infected cell lysates showed that the IgG from SSPE brain contained activity specific for measles virus protein. The abundance, purity and functional activity of IgG extracted from SSPE and MS brain indicate that IgG extracted from the brain of humans with an inflammatory disease of unknown etiology can be used to identify its corresponding antigen. PMID:9389401

  8. Optimization of the cutoff value for a commercial anti-dengue virus IgG immunoassay.

    PubMed

    Marrero-Santos, Karla M; Beltrán, Manuela; Carrión-Lebrón, Jessica; Sanchez-Vegas, Carolina; Hamer, Davidson H; Barnett, Elizabeth D; Santiago, Luis M; Hunsperger, Elizabeth A

    2013-03-01

    A commercial anti-dengue virus (anti-DENV) indirect IgG enzyme-linked immunosorbent assay (ELISA) for serological diagnosis was evaluated for its utility in determining previous DENV exposure in U.S. travelers. The Boston Area Travel Medicine Network clinics used Focus Diagnostics anti-DENV IgG ELISA to measure anti-DENV IgG antibodies in 591 pretravel specimens from U.S. residents who had traveled to countries where dengue is endemic. When using the manufacturer's index cutoff value for this ELISA, false-positive results were observed that overestimated the perceived past DENV exposure in U.S. travelers. Validation of 121 of these anti-DENV IgG results by plaque reduction neutralization test (PRNT) was used for receiver operating characteristic (ROC) curve optimization of the index cutoff value from 1 to 3.0, improving the specificity of the anti-DENV IgG ELISA from 24% to 95.7%. Additionally, previous vaccination with yellow fever virus contributed to 52.8% of the false-positive rate in the anti-DENV IgG ELISA results. Optimization of the cutoff value of the anti-DENV IgG ELISA provided better interpretation and confidence in the results and eliminated the need for confirmation by PRNT. The travel history of U.S. travelers was also useful for categorizing these travelers into groups for analysis of previous DENV exposure. PMID:23302742

  9. Changes in Healthy Human IgG Fc-Glycosylation after Birth and during Early Childhood.

    PubMed

    de Haan, Noortje; Reiding, Karli R; Driessen, Gertjan; van der Burg, Mirjam; Wuhrer, Manfred

    2016-06-01

    Glycosylation on the fragment crystallizable (Fc) region of immunoglobulin G (IgG) has a large influence on the interaction of the antibody with Fc gamma receptors (FcγRs). IgG consists of four subclasses that all have distinct affinities for the different FcγRs. Knowledge about the Fc-glycosylation in healthy human is valuable as reference for new biomarkers and in the design of biopharmaceuticals that rely on IgG Fc-glycosylation. Previously, subclass-specific characterization of IgG Fc-glycosylation was performed for healthy adults, pregnant women, and newborns. For young healthy children, however, the subclass-specific description of IgG Fc-glycosylation is still lacking. Therefore, we performed the IgG subclass-specific analysis of the Fc-glycosylation of 130 healthy humans between birth and 40 years of age, including 22 samples derived from the umbilical cords of newborns. The analysis was performed by a previously published matrix-assisted laser desorption/ionization (MALDI)-time-of-flight (TOF)-mass spectrometry (MS) workflow, including a derivatization step for the linkage-specific stabilization of sialic acids. The characterization revealed that when children start to produce their own IgG they have a decreased galactosylation, sialylation, and bisection and an increased fucosylation compared with newborns. During childhood, the fucosylation and sialylation decrease, whereas bisection increases and galactosylation stays constant. PMID:27161864

  10. Retroperitoneal disorders associated with IgG4-related autoimmune pancreatitis.

    PubMed

    Hara, Noboru; Kawaguchi, Makoto; Takeda, Keisuke; Zen, Yoh

    2014-11-28

    IgG4-related autoimmune pancreatitis is frequently accompanied by relevant lesions in the genitourinary tract and retroperitoneal organs, which cause various clinical problems, ranging from non-specific back pain or bladder outlet obstruction to renal failure. The diagnosis of IgG4-related retroperitoneal fibrosis requires a multidisciplinary approach, including serological tests, histological examination, imaging analysis, and susceptibility to steroid therapy. Radiological examinations are helpful to diagnose this condition, but surgical resection is occasionally unavoidable to exclude malignancy, particularly for patients with isolated retroperitoneal involvement. Steroid therapy is the treatment of choice for this condition, the same as for other manifestations of IgG4-related disease. For patients with severe ureteral obstruction, additional ureteral stenting needs to be considered prior to steroid therapy to preserve the renal function. Some papers have suggested that IgG4-related disease can affect male reproductive organs including the prostate and testis. IgG4-related prostatitis usually causes lower urinary tract symptoms, such as dysuria and pollakisuria. Patients sometimes state that corticosteroids given for IgG4-related disease at other sites relieve their lower urinary tract symptoms, which leads us to suspect prostatic involvement in this condition. Because of the limited number of publications available, further studies are warranted to better characterize IgG4-related disease in male reproductive organs. PMID:25469023

  11. Early and late neonatal septicaemia.

    PubMed Central

    Placzek, M M; Whitelaw, A

    1983-01-01

    Between 1979 and 1982 we reviewed 1000 consecutive admissions to the neonatal intensive care unit of this hospital. Sixty five infants had positive blood cultures. Mortality was 70% among 17 infants who had septicaemia in the first 48 hours of life and for whom appropriate treatment may have been too late because of difficulties of early diagnosis. In the remaining 48 infants mortality was 12%, septicaemia occurred later, and was associated with Staphylococcus epidermidis (56%) and with the presence of an intravascular catheter (50%). PMID:6625634

  12. A Rapid Method to Characterize Mouse IgG Antibodies and Isolate Native Antigen Binding IgG B Cell Hybridomas.

    PubMed

    Liu, Haolin; White, Janice; Crawford, Frances; Jin, Niyun; Ju, Xiangwu; Liu, Kangtai; Jiang, Chengyu; Marrack, Philippa; Zhang, Gongyi; Kappler, John W

    2015-01-01

    B cell hybridomas are an important source of monoclonal antibodies. In this paper, we developed a high-throughput method to characterize mouse IgG antibodies using surface plasmon resonance technology. This assay rapidly determines their sub-isotypes, whether they bind native antigen and their approximate affinities for the antigen using only 50 μl of hybridoma cell culture supernatant. Moreover, we found that mouse hybridomas secreting IgG antibodies also have membrane form IgG expression without Igα. Based on this surface IgG, we used flow cytometry to isolate rare γ2a isotype switched variants from a γ2b antibody secreting hybridoma cell line. Also, we used fluorescent antigen to single cell sort antigen binding hybridoma cells from bulk mixture of fused hybridoma cells instead of the traditional multi-microwell plate screening and limiting dilution sub-cloning thus saving time and labor. The IgG monoclonal antibodies specific for the native antigen identified with these methods are suitable for in vivo therapeutic uses, but also for sandwich ELISA assays, histology, flow cytometry, immune precipitation and x-ray crystallography. PMID:26317987

  13. Neonatal tetanus associated with skin infection.

    PubMed

    Maharaj, M; Dungwa, N

    2016-09-01

    A 1-week-old infant was brought to a regional hospital with a history of recurrent seizures following lower abdominal septic skin infection. She was found to have neonatal tetanus, and a spatula test was positive. The tetanus infection was associated with a superficial skin infection, common in neonates. Treatment included sedatives (diazepam, chlorpromazine, phenobarbitone and morphine), muscle relaxants, antibiotics and ventilation in the neonatal intensive care unit. Intrathecal and intramuscular immunoglobulin were given, and the wound was treated. The infant recovered, with no seizures by the 16th day from admission, and was off the ventilator by the 18th day. This was shorter than the usual 3 - 4 weeks for neonates with tetanus at the hospital. The question arises whether tetanus immunisation should be considered in infants with skin infections, which frequently occur in the neonatal period. PMID:27601113

  14. Stem Cells for Neonatal Brain Disorders.

    PubMed

    Ahn, So Yoon; Chang, Yun Sil; Park, Won Soon

    2016-01-01

    Despite recent advances in neonatal intensive care medicine, neonatal brain injury resulting from intraventricular hemorrhage or hypoxic-ischemic encephalopathy remains a major cause of neonatal mortality and neurologic morbidities in survivors. Several studies have indicated that stem cell therapy is a promising novel therapy for neonatal brain injury resulting from these disorders. This review summarizes recent advances in stem cell research for treating neonatal brain injury due to intraventricular hemorrhage or hypoxic-ischemic encephalopathy with a particular focus on preclinical data, covering important issues for clinical translation such as optimal cell type, route, dose and timing of stem cell therapy, and translation of these preclinical results into a clinical trial. PMID:27251746

  15. Distribution of Cytomegalovirus Genotypes among Neonates Born to Infected Mothers in Islamabad, Pakistan

    PubMed Central

    Mujtaba, Ghulam; Khurshid, Adnan; Sharif, Salmaan; Alam, Muhammad Masroor; Aamir, Uzma Bashir; Shaukat, Shahzad; Angez, Mehar; Rana, Muhammad Suleman; Umair, Massab; Shah, Aamer Ali; Zaidi, Syed Sohail Zahoor

    2016-01-01

    Background Congenital cytomegalovirus (cCMV) infection contributes to considerable long-term sequelae in neonates and children all over the world. The association between viral genotypes and severity of clinical cytomegalovirus (CMV) infection is yet to be defined. The objective of this study was to find the impact of active CMV infection during pregnancy and the clinical significance of genotypes in neonates with congenital cytomegalovirus infections in Pakistan. Methods A total of 409 blood samples from pregnant women seeking health care services at the two antenatal hospitals of Islamabad during January to December 2012 were tested by ELISA and nested-PCR. Pregnant women with active infection (detected as IgM positive, PCR positive or positive on both assays) were followed until delivery, to detect the outcome of overt cCMV infection in neonates. Genetic characterization of CMV strains was performed by sequence analysis of envelope glycoproteins: gB, gN and gH to detect the contributing CMV genotypes. Results The seroprevalence of anti-CMV IgG and IgM was 97.5% (399 out of 409) and 12.7% (52 out of 409), respectively, while 20% (82/409) pregnant women were found positive for CMV DNA by PCR. Logistic regression analysis showed a significant association of active infection with parity [OR = 2.56, 95% CI = 1.82–2.62, p = 0.04], febrile illness [OR = 1.84, 95% CI = 1.76–3.65, p = 0.01] and jaundice [OR = 22.5, 95% CI = 4.53–85.02, p = 0.002]. We were able to isolate virus in 41 out of 70 neonates; 36.6% (15 out of 41) of them were symptomatic at birth while 63.4% (26 out of 41) were asymptomatic. The most prominent clinical feature observed in symptomatic neonates was hepatosplenomegaly (26.6%; 4 out of 15). All three genotypes gB, gN and gH were found with the highest frequency of gB1 genotype, found in 75% infants with hepatic damage. Phylogenetic analysis of Pakistani strains showed 96%-100% homology to their prototype strains. Conclusions Active CMV

  16. Induction of IgG memory responses with polyvinylpyrrolidone (PVP) is antigen dose dependent

    SciTech Connect

    Lite, H.S.; Braley-Mullen, H.

    1981-03-01

    Irradiated recipients of spleen cells from mice primed with a very low dose (0.0025 ..mu../g) of the thymus-independent (TI) antigen polyvinylpyrrolidone (PVP) produced PVP-specific IgG memory responses after secondary challenge with a T-dependent (TD) form of PVP, PVP-HRBC. The IgG memory responses induced by low doses of PVP were similar in magnitude to those induced by the TD antigen PVP-HRBC. The induction of IgG memory by the TI form of antigen was markedly dependent on the dose of PVP used to prime donor mice. Spleen cells from mice primed with an amount of PVP (0.25 ..mu..g) that induces an optimal primary IgM response did not produce significant IgG antibody after challenge with PVP-HRBC. The inability of higher doses of PVP to induce IgG memory may be due, at least in part, to the fact that such doses of PVP were found to induce tolerance in PVP-specific B cells and could suppress the induction of memory induced by PVP-HRBC. Low doses of PVP did not interfere with the induction of memory by PVP-HRBC. Expression of IgG memory responses in recipients of PVP-HRBC or low-dose PVP-primed cells was found to be T cell dependent. Moreover, only primed T cells could reconstitute the respnse of recipients of primed B cells, suggesting that the ability of PVP to induce IgG memory may be related to its ability to prime T helper cells. Expression of the IgG memory response in recipient mice also required the use of a TD antigen for secondary challenge, i.e., mice challenged with PVP did not develop IgG.

  17. Clinicopathological features of Riedel's thyroiditis associated with IgG4-related disease in Japan.

    PubMed

    Takeshima, Ken; Inaba, Hidefumi; Ariyasu, Hiroyuki; Furukawa, Yasushi; Doi, Asako; Nishi, Masahiro; Hirokawa, Mitsuyoshi; Yoshida, Akira; Imai, Ryoukichi; Akamizu, Takashi

    2015-01-01

    Riedel's thyroiditis (RT) is a rare chronic fibrosing disorder characterized by a hard, infiltrative lesion in the thyroid gland, which is often associated with multifocal fibrosclerosis. Immunoglobulin G4-related disease (IgG4-RD) is typified by infiltration of IgG4-positive plasma cells into multiple organs, resulting in tissue fibrosis and organ dysfunction. In order to evaluate the clinicopathological features of RT and its relationship with IgG4-RD, we performed a Japanese literature search using the keywords "Riedel" and "Riedel's thyroiditis." We used the electronic databases Medline and Igaku Chuo Zasshi, the latter of which is the largest medical literature database in Japan. The diagnosis of RT was based on the presence of a fibroinflammatory process with extension into surrounding tissues. Only 10 patients in Japan fulfilled RT diagnostic criteria during the 25-year period between 1988 and 2012. Two patients with confirmed IgG4/IgG immunohistochemical findings demonstrated 43 and 13 IgG4-positive plasma cells per high-power field, respectively, and the IgG4-positive/IgG-positive plasma cell ratios of 20% and less than 5%. Of the 10 patients with RT, two received glucocorticoids, one of whom experienced marked shrinkage of the thyroid lesion. One patient had extra-thyroid involvement in the form of retroperitoneal fibrosis. Although the clinicopathological features of RT suggest that IgG4-RD may be the underlying condition in some cases, further investigation is needed to clarify the etiology of RT in relation to IgG4-RD. PMID:26052139

  18. IgG4-related tubulointerstitial nephritis associated with only lymphadenopathy and without elevated serum IgG4 or renal imaging abnormalities: a case report and literature review.

    PubMed

    Qiao, Xi; Wang, Lihua; Wang, Chen; Gao, Lifang; Yao, Shulei; Wu, Liran; Zhang, Xiaoqin

    2015-01-01

    IgG4-related tubulointerstitial nephritis (IgG4-TIN) is the most common renal manifestation of IgG4-related kidney disease (IgG4-RKD) and may cause acute or chronic renal dysfunction. Imaging often shows heterogeneous densities in the kidneys, such as a mass or multiple nodules. Serology usually demonstrates high levels of serum IgG4 and total IgG. Most patients have other organs involvement by IgG4 related disease. Although lymphadenopathy is frequently observed in patients with IgG4-TIN, it is rarely presented as the only extrarenal lesion. Herein, we present a rare case of IgG4-TIN associated with only lymphadenopathy and without elevated serum IgG4 or renal imaging abnormalities. A 61-year-old Chinese man was admitted to our hospital with seven months history of generalized lymphadenopathy and five months history of renal dysfunction. His renal imaging was normal. He had no current or previous clinical, radiographic, and/or histologic evidence of other organ involvement except for the lymphadenopathy. Renal biopsy indicated plasma cell-rich TIN with an increased number of IgG4-positive plasma cells and storiform fibrosis. Repeated lymph nodes biopsy revealed IgG4-related lymphadenopathy. However, he did not have elevated serum IgG4 or total IgG levels. Oral prednisone therapy improved his renal function and lymphadenopathy. These findings supported our final diagnosis of IgG4-TIN. Clinicians should be aware of this condition and steroid therapy should be considered for such patients. An early diagnosis and appropriate therapy can induce remission and preserve renal function. PMID:26770608

  19. Tissue expression profile of human neonatal Fc receptor (FcRn) in Tg32 transgenic mice.

    PubMed

    Fan, Yao-Yun; Avery, Lindsay B; Wang, Mengmeng; O'Hara, Denise M; Leung, Sheldon; Neubert, Hendrik

    2016-07-01

    The neonatal Fc receptor (FcRn) is a homeostatic receptor responsible for prolonging immunoglobulin G (IgG) half-life by protecting it from lysosomal degradation and recycling it to systemic circulation. Tissue-specific FcRn expression is a critical parameter in physiologically-based pharmacokinetic (PBPK) modeling for translational pharmacokinetics of Fc-containing biotherapeutics. Using online peptide immuno-affinity chromatography coupled with high resolution mass spectrometry, we established a quantitative FcRn tissue protein expression profile in human FcRn (hFcRn) transgenic mice, Tg32 homozygous and hemizygous strains. The concentration of hFcRn across 14 tissues ranged from 3.5 to 111.2 pmole per gram of tissue. Our hFcRn quantification data from Tg32 mice will enable a more refined PBPK model to improve the accuracy of human PK predictions for Fc-containing biotherapeutics. PMID:27104806

  20. Intracranial spread of IgG4-related disease via skull base foramina.

    PubMed

    Rice, C M; Spencer, T; Bunea, G; Scolding, N J; Sloan, P; Nath, U

    2016-06-01

    IgG4-related disease (IgG4-RD) is a newly recognised, multiorgan, inflammatory disease, and its full clinical spectrum remains undefined. We present a biopsy-proven case of IgG4-RD presenting with a parapharyngeal mass with intracranial extension and possible involvement of the brain parenchyma. We highlight the importance of considering the diagnosis in those presenting with tumefactive lesions, leptomeningitis or pachymeningitis and emphasise the value of securing a tissue diagnosis so that appropriate long-term treatment can be instigated and complications avoided. PMID:26856357

  1. IgG antibodies to Aspergillus fumigatus in cystic fibrosis: a laboratory correlate of disease activity.

    PubMed Central

    Forsyth, K D; Hohmann, A W; Martin, A J; Bradley, J

    1988-01-01

    Serum was collected from 50 patients with cystic fibrosis, and IgG antibodies to Aspergillus fumigatus were measured by enzyme linked immunosorbent assay (ELISA). In addition, total IgE and Aspergillus specific IgE antibodies were measured in 41 of the 50. A close association was found between pulmonary function and clinical state, and IgG antibodies to Aspergillus. There was no association between pulmonary function or clinical state and IgE antibodies. It is postulated that in patients with cystic fibrosis, Aspergillus fumigatus may contribute to deterioration in pulmonary function by local pathogenicity, or by hypersensitivity mechanisms mediated by IgG. PMID:3046514

  2. Serum immunoglobulins, IgG subclasses, isohemagglutinins and complement-3 levels in patients with thalassemia major.

    PubMed

    Vergin, C; Kutukculer, N; Cetingul, N; Nisli, G; Caglayan, S; Oztop, S

    1997-01-01

    Serum IgG, IgM, IgA, IgG subclasses (IgG1, G2, G3, G4), isohemagglutinins and complement-3 concentrations were measured in 23 beta-thalassemic patients suffering from recurrent infections. No significant abnormalities were found in these humoral immunity investigations, both in splenectomized and non-splenectomized patients. On the other hand, iron overload or repeated blood transfusions were not found to down-regulate the humoral immune system of thalassemic patients. PMID:10771839

  3. Cleavage of IgG1 in GCF is associated with presence of Porphyromonas gingivalis

    PubMed Central

    Guentsch, Arndt; Hirsch, Christiane; Pfister, Wolfgang; Vincents, Bjarne; Abrahamson, Magnus; Sroka, Aneta; Potempa, Jan; Eick, Sigrun

    2012-01-01

    Background and Objectives Immunoglobulin (Ig) G1 plays an important role in the adaptive immune response. Kgp, a lysine-specific cysteine protease from Porphyromonas gingivalis, specifically hydrolyses IgG1 heavy chains. The purpose of this study was to examine whether cleavage of IgG1 occurs in gingival crevicular fluid (GCF) in vivo, and whether there is any association with the presence of P. gingivalis and other periodontopathogens. Material and methods GCF was obtained from nine patients with aggressive periodontitis, nine with chronic periodontitis, and five periodontally-healthy individuals. The bacterial loads of P. gingivalis, Aggregatibacter actinomycetemcomitans, Treponema denticola, Prevotella intermedia, and Tannerella forsythia were analysed by real-time PCR, and the presence and cleavage of IgG1 and IgG2 were determined using Western blotting. Kgp levels were measured by ELISA. Results Cleaved IgG1 was identified in the GCF from 67% of patients with aggressive periodontitis and in 44% of patients with chronic periodontitis. By contrast, no cleaved IgG1 was detectable in the healthy controls. No degradation of IgG2 was detected in any of the samples, regardless of health status. P. gingivalis was found in high numbers in all samples in which cleavage of IgG1 was detected (p < 0.001 compared with samples with no IgG cleavage). Furthermore, high numbers of T. forsythia and P. intermedia were also present in these samples. The level of Kgp in the GCF correlated with the load of P. gingivalis (r = 0.425, p < 0.01). The presence of Kgp (range 0.07–10.98 ng/ml) was associated with proteolytic fragments of IgG1 (p < 0.001). However, cleaved IgG1 was also detected in samples with no detectable Kgp. Conclusion In patients with periodontitis cleavage of IgG1 occurs in vivo and may suppress antibody-dependent antibacterial activity in subgingival biofilms especially those colonized by P. gingivalis. PMID:23116446

  4. Diagnostic Value of Serum IgG4 for IgG4-Related Disease: A PRISMA-compliant Systematic Review and Meta-analysis.

    PubMed

    Hao, Mingju; Liu, Min; Fan, Gaowei; Yang, Xin; Li, Jinming

    2016-05-01

    Many studies about serum IgG4 for the diagnosis of IgG4-related disease (IgG4-RD) have been reported. However, these studies had relatively small sample sizes and the diagnostic accuracy values varied much between them.The aim of this study was to perform a meta-analysis to evaluate the diagnostic value of serum IgG4 for IgG4-RD.We conducted a search of relevant articles using MEDLINE, EMBASE, Web of Science, SCOPUS, and Cochrane Library databases published before December 2015.Studies those assessed the diagnostic accuracy of serum IgG4 for IgG4-RD and those provided the cut-off value for serum IgG4 were included.Data were synthesized using the random-effect model. Statistical analysis was performed using STATA with the MIDAS module and Meta-DiSc 1.4 software.A total of 9 case-control studies were analyzed, which included 1235 patients with IgG4-RD and 5696 overall controls. The pooled estimate, for a cut-off value ranged from 135 to 144 mg/dL, produced a sensitivity of 87.2% (95% CI, 85.2-89.0%) and a specificity of 82.6% (95% CI, 81.6-83.6%). The positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were 6.48 (95% CI, 3.98-10.57), 0.14 (95% CI, 0.09-0.21), and 45.15 (95% CI, 23.41-87.06), respectively. The area under the curve (AUC) of the summary receiver operating characteristic curve (SROC) was 0.94 (0.92-0.96). When a cut-off value of 2-fold the upper limit of normal was used (ranged from 270 to 280 mg/dL), the pooled sensitivity was 63% (95% CI, 60.0-66.0%), and the specificity was 94.8% (95% CI, 94.1-95.4%). The PLR, NLR, and DOR were 13.3 (95% CI, 7.39-24.0), 0.41 (95% CI, 0.29-0.58) and 33.42 (95% CI, 13.88-80.43), respectively. The AUC of the SROC was 0.92 (0.90-0.94).Only a relatively small number of studies were included, and significant heterogeneity was observed in this meta-analysis.Serum IgG4 is a modestly effective marker to diagnose IgG4-RD. Doubling the cut-off value for IgG4 could not improve the

  5. Arrhythmias presenting in neonatal lupus.

    PubMed

    Brucato, A; Previtali, E; Ramoni, V; Ghidoni, S

    2010-09-01

    Perfusion of human foetal heart with anti-Ro/SSA antibodies induces transient heart block. Anti-Ro/SSA antibodies may cross-react with T- and L-type calcium channels, and anti-p200 antibodies may cause calcium to accumulate in rat heart cells. These actions may explain a direct electrophysiological effect of these antibodies. Congenital complete heart block is the more severe manifestation of so-called "Neonatal Lupus". In clinical practice, it is important to distinguish in utero complete versus incomplete atrioventricular (AV) block, as complete AV block to date is irreversible, while incomplete AV block has been shown to be potentially reversible after fluorinated steroid therapy. Another issue is the definition of congenital AV block, as cardiologists have considered congenital blocks detected months or years after birth. We propose as congenital blocks detected in utero or within the neonatal period (0-27 days after birth). The possible detection of first degree AV block in utero, with different techniques, might be a promising tool to assess the effects of these antibodies. Other arrhythmias have been described in NL or have been linked to anti-Ro/SSA antibodies: first degree AV block, in utero and after birth, second degree (i.e. incomplete block), sinus bradycardia and QT prolongation, both in infants and in adults, ventricular arrhythmias (in adults). Overall, these arrhythmias have not a clinical relevance, but are important for research purposes. PMID:20696016

  6. Neonatal Incidence of Hip Dysplasia

    PubMed Central

    Peled, Eli; Eidelman, Mark; Katzman, Alexander

    2008-01-01

    The advantages of sonographic examination are well known, but its main disadvantage is that it might lead to overdiagnosis, which might cause overtreatment. Variations in the incidence of developmental dysplasia of the hip are well known. We ascertained the incidence of neonatal sonographic developmental dysplasia of the hip without considering the development of those joints during followup. All 45,497 neonates (90,994 hips) born in our institute between January 1992 and December 2001 were examined clinically and sonographically during the first 48 hours of life. Sonography was performed according to Graf’s method, which considers mild hip sonographic abnormalities as Type IIa. We evaluated the different severity type incidence pattern and its influence on the total incidence during and between the investigated years. According to our study, sonographic Type IIa has major effects on the incidence of overall developmental dysplasia of the hip with a correlation coefficient of 0.95, whereas more severe sonographic abnormalities show relatively stable incidence patterns. Level of Evidence: Level I, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence. PMID:18288551

  7. Global health and neonatal nursing: a personal journey.

    PubMed

    Kenner, Carole; Boykova, Marina

    2012-09-01

    The need for improvement of neonatal nursing care is a global issue. Neonatal nurses have an important role in optimizing these health outcomes for neonates and their families. This article describes the personal journey of one nurse and her mentee. It describes how a passion for neonates led to global policy work. PMID:22895204

  8. Timing of neonatal seizures and intrapartum obstetrical factors.

    PubMed

    Scher, Mark S; Steppe, Doris A; Beggarly, Marquita

    2008-06-01

    One hundred ninety-three neonates with seizures were available on a neonatal seizure database, which included intrapartum and neonatal factors such as labor duration, fetal heart rate abnormalities, cord blood gas values, Apgar scores and clinical signs of encephalopathy. Regression analyses (analysis of variance) were performed on the entire cohort as well as specific subsets of neonates (eg, neonatal encephalopathy vs no encephalopathy) to assess the relationship between seizure timing and intrapartum/neonatal factors. Seizures were noted earlier for the encephalopathic group than for the nonencephalopathic group. No significant differences were noted for any intrapartum or neonatal factors. Timing of neonatal seizures, with or without an encephalopathy occurs within the first 2 days after birth and is independent of selected intrapartum and neonatal factors, underscoring recent task force recommendations concerning neonatal encephalopathy. Factors other than intrapartum events more likely contribute to the encephalopathic repertoire of the newborn, including seizures. PMID:18281619

  9. The Korean Neonatal Network: An Overview

    PubMed Central

    Chang, Yun Sil; Park, Hyun-Young

    2015-01-01

    Currently, in the Republic of Korea, despite the very-low-birth rate, the birth rate and number of preterm infants are markedly increasing. Neonatal deaths and major complications mostly occur in premature infants, especially very-low-birth-weight infants (VLBWIs). VLBWIs weigh less than 1,500 g at birth and require intensive treatment in a neonatal intensive care unit (NICU). The operation of the Korean Neonatal Network (KNN) officially started on April 15, 2013, by the Korean Society of Neonatology with support from the Korea Centers for Disease Control and Prevention. The KNN is a national multicenter neonatal network based on a prospective web-based registry for VLBWIs. About 2,000 VLBWIs from 60 participating hospital NICUs are registered annually in the KNN. The KNN has built unique systems such as a web-based real-time data display on the web site and a site-visit monitoring system for data quality surveillance. The KNN should be maintained and developed further in order to generate appropriate, population-based, data-driven, health-care policies; facilitate active multicenter neonatal research, including quality improvement of neonatal care; and ultimately lead to improvement in the prognosis of high-risk newborns and subsequent reduction in health-care costs through the development of evidence-based neonatal medicine in Korea. PMID:26566355

  10. Laser Photoradiation Therapy For Neonatal Jaundice

    NASA Astrophysics Data System (ADS)

    Hamza, Mostafa; Hamza, Mohammad

    1987-04-01

    This paper describes our leading experience in the clinical application of laser in the treatment of neonatal jaundice. Currently, the irradiation of jaundiced infants during neonatal life to fluorescent light is the most common treatment of neonatal hyperbilirubinemia. The authors have investigated the photodegradation of bilirubin by laser in vitro and in Gunn rats before embarking on its clinical application in the treatment of jaundice in the new born child. This work was done to study the theraputic effect of laser compared to the currently used phototherapy in the treatment of neonatal jaundice. We selected 16 full term neonates with jaundice to be the subject of this study. The neonates of the study were devided into two groups. The first group was treated with continuous phototherapy . The second group recieved photoradiation therapy with gas laser The laser used was a CW argon-ion laser tuned to oscillate at 488.0 nm wavelength. This wavelength selection was based on our previous studies on the effect of laser irradiation of Gunn rats at different wavelengths. Comparison of the results of both methods of treatment will be reported in detail. The advantages and limitations of laser photoradiation therapy for neonatal jaundice will be discussed.

  11. An immunologic assessment of brain-associated IgG in senile cerebral amyloidosis.

    PubMed

    Goust, J M; Mangum, M; Powers, J M

    1984-09-01

    Frontal and occipital lobes were taken within four hours of death from four senile patients (77-94 years) and frozen at -70 degrees C. After thawing at room temperature, gray and white matter were separated and subjected to sequential elution at pH 7.4 and pH 2.5. The eluates were processed for isoelectric focusing on 2.5% polyacrylamide gels and stained with silver nitrate; immunoblotting was done on agarose gels and stained by immunoperoxidase for IgG and light chains. Quantitation of the amount of IgG present in neutral and acidic eluates was performed by immunonephelometry and ELISA. Only the neutral eluates contained significant amounts of IgG, which were usually polyclonal. These data indicate that IgG associated with senile cerebral amyloid are not bound to any brain or vascular component and the data do not support the occurrence of an intraparenchymal immune response. PMID:6381655

  12. In vitro and in vivo modifications of recombinant and human IgG antibodies

    PubMed Central

    Liu, Hongcheng; Ponniah, Gomathinayagam; Zhang, Hui-Min; Nowak, Christine; Neill, Alyssa; Gonzalez-Lopez, Nidia; Patel, Rekha; Cheng, Guilong; Kita, Adriana Z; Andrien, Bruce

    2014-01-01

    Tremendous knowledge has been gained in the understanding of various modifications of IgG antibodies, driven mainly by the fact that antibodies are one of the most important groups of therapeutic molecules and because of the development of advanced analytical techniques. Recombinant monoclonal antibody (mAb) therapeutics expressed in mammalian cell lines and endogenous IgG molecules secreted by B cells in the human body share some modifications, but each have some unique modifications. Modifications that are common to recombinant mAb and endogenous IgG molecules are considered to pose a lower risk of immunogenicity. On the other hand, modifications that are unique to recombinant mAbs could potentially pose higher risk. The focus of this review is the comparison of frequently observed modifications of recombinant monoclonal antibodies to those of endogenous IgG molecules. PMID:25517300

  13. Opsonic capacity of foal serum for the two neonatal pathogens Escherichia coli and Actinobacillus equuli.

    PubMed

    Gröndahl, G; Sternberg, S; Jensen-Waern, M; Johannisson, A

    2001-11-01

    Two of the most commonly isolated foal pathogens are Escherichia coli and Actinobacillus equuli. The hypothesis tested in this study was that young foals carry a lower opsonic capacity for these bacteria compared to adult horses. A flow-cytometric method for the phagocytosis of these by equine neutrophils was established. The opsonic capacity of serum from healthy foals from birth to age 6 weeks was evaluated and related to the concentrations of IgGa and IgGb. Phagocytosis of yeast was used as a control. Serum was required for phagocytosis, with higher concentrations for E. coli than for A. equuli. Ingestion of colostrum led to a significantly higher serum opsonic capacity. After that, there was no consistent age-related trend for opsonic capacity for the different microbes. Foal serum showed similar or higher opsonisation of E. coli and A. equuli compared to serum from mature individuals. During the studied period, the predominance among IgG subisotypes switched from IgGb to IgGa. Although the overall correlation between concentrations of IgG subisotypes and serum opsonic capacity was poor, sera with IgGb levels below 1.9 mg/ml induced lower opsonisation of E. coli and yeast, but not of A. equuli. Complement activation was important for opsonisation of all tested microbes. The results of this study are significant to the understanding of a key immunological facet in the pathophysiology of equine neonatal septicaemia in clinical practice. PMID:11770988

  14. Materno-Fetal Transfer of Preproinsulin Through the Neonatal Fc Receptor Prevents Autoimmune Diabetes.

    PubMed

    Culina, Slobodan; Gupta, Nimesh; Boisgard, Raphael; Afonso, Georgia; Gagnerault, Marie-Claude; Dimitrov, Jordan; Østerbye, Thomas; Justesen, Sune; Luce, Sandrine; Attias, Mikhaël; Kyewski, Bruno; Buus, Søren; Wong, F Susan; Lacroix-Desmazes, Sebastien; Mallone, Roberto

    2015-10-01

    The first signs of autoimmune activation leading to β-cell destruction in type 1 diabetes (T1D) appear during the first months of life. Thus, the perinatal period offers a suitable time window for disease prevention. Moreover, thymic selection of autoreactive T cells is most active during this period, providing a therapeutic opportunity not exploited to date. We therefore devised a strategy by which the T1D-triggering antigen preproinsulin fused with the immunoglobulin (Ig)G Fc fragment (PPI-Fc) is delivered to fetuses through the neonatal Fc receptor (FcRn) pathway, which physiologically transfers maternal IgGs through the placenta. PPI-Fc administered to pregnant PPIB15-23 T-cell receptor-transgenic mice efficiently accumulated in fetuses through the placental FcRn and protected them from subsequent diabetes development. Protection relied on ferrying of PPI-Fc to the thymus by migratory dendritic cells and resulted in a rise in thymic-derived CD4(+) regulatory T cells expressing transforming growth factor-β and in increased effector CD8(+) T cells displaying impaired cytotoxicity. Moreover, polyclonal splenocytes from nonobese diabetic (NOD) mice transplacentally treated with PPI-Fc were less diabetogenic upon transfer into NOD.scid recipients. Transplacental antigen vaccination provides a novel strategy for early T1D prevention and, further, is applicable to other immune-mediated conditions. PMID:25918233

  15. Structure-based mutagenesis reveals the albumin-binding site of the neonatal Fc receptor

    PubMed Central

    Andersen, Jan Terje; Dalhus, Bjørn; Cameron, Jason; Daba, Muluneh Bekele; Plumridge, Andrew; Evans, Leslie; Brennan, Stephan O.; Gunnarsen, Kristin Støen; Bjørås, Magnar; Sleep, Darrell; Sandlie, Inger

    2012-01-01

    Albumin is the most abundant protein in blood where it has a pivotal role as a transporter of fatty acids and drugs. Like IgG, albumin has long serum half-life, protected from degradation by pH-dependent recycling mediated by interaction with the neonatal Fc receptor, FcRn. Although the FcRn interaction with IgG is well characterized at the atomic level, its interaction with albumin is not. Here we present structure-based modelling of the FcRn–albumin complex, supported by binding analysis of site-specific mutants, providing mechanistic evidence for the presence of pH-sensitive ionic networks at the interaction interface. These networks involve conserved histidines in both FcRn and albumin domain III. Histidines also contribute to intramolecular interactions that stabilize the otherwise flexible loops at both the interacting surfaces. Molecular details of the FcRn–albumin complex may guide the development of novel albumin variants with altered serum half-life as carriers of drugs. PMID:22215085

  16. Effects of allergic diseases and age on the composition of serum IgG glycome in children.

    PubMed

    Pezer, Marija; Stambuk, Jerko; Perica, Marija; Razdorov, Genadij; Banic, Ivana; Vuckovic, Frano; Gospic, Adrijana Miletic; Ugrina, Ivo; Vecenaj, Ana; Bakovic, Maja Pucic; Lokas, Sandra Bulat; Zivkovic, Jelena; Plavec, Davor; Devereux, Graham; Turkalj, Mirjana; Lauc, Gordan

    2016-01-01

    It is speculated that immunoglobulin G (IgG) plays a regulatory role in allergic reactions. The glycans on the Fc region are known to affect IgG effector functions, thereby possibly having a role in IgG modulation of allergic response. This is the first study investigating patients' IgG glycosylation profile in allergic diseases. Subclass specific IgG glycosylation profile was analyzed in two cohorts of allergen sensitized and non-sensitized 3- to 11-year-old children (conducted at University of Aberdeen, UK and Children's Hospital Srebrnjak, Zagreb, Croatia) with 893 subjects in total. IgG was isolated from serum/plasma by affinity chromatography on Protein G. IgG tryptic glycopeptides were analyzed by liquid chromatography electrospray ionization mass spectrometry. In the Zagreb cohort IgG glycome composition changed with age across all IgG subclasses. In both cohorts, IgG glycome composition did not differ in allergen sensitized subjects, nor children sensitized to individual allergens, single allergen mean wheal diameter or positive wheal sum values. In the Zagreb study the results were also replicated for high total serum IgE and in children with self-reported manifest allergic disease. In conclusion, our findings demonstrate no association between serum IgG glycome composition and allergic diseases in children. PMID:27616597

  17. 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. PMID:27235354

  18. Determination of the IgG index for the detection of intrathecal immunoglobulin synthesis in dogs using an ELISA.

    PubMed

    Tipold, A; Pfister, H; Vandevelde, M

    1993-01-01

    The IgG index is a calculated quotient using IgG and albumin contents of cerebrospinal fluid (CSF) and serum to detect intrathecal IgG synthesis, which is important in the diagnosis of inflammatory infectious diseases of the central nervous system (CNS). An ELISA to measure IgG and albumin contents in blood and CSF was developed to determine the IgG index. Twenty-three normal dogs and 98 dogs with various neurological diseases were examined. In most dogs with infectious inflammatory diseases, with the exception of the acute form of nervous canine distemper, there was an elevation of the IgG index. Tumours of the CNS had an IgG index within the normal range. An elevation was found in lymphoid tumours or meningiomas with secondary cellular infiltration. Degenerative diseases, spinal cord compression and ischaemic myelopathy due to fibrocartilagenous embolism had normal or only slightly elevated IgG indices. In seven cases with inflammatory lesions there was no obvious CSF pleocytosis but the IgG index was elevated. In 17 cases in which infectious inflammatory disease was suspected, based on elevated CSF cell counts, inflammation could be excluded after determination of the IgG index. The reproducibility of the technique was found to be good and, considering the limited amount of time, expense and effort required, the determination of the IgG index in dogs is a useful extension of the conventional CSF examination. PMID:8434146

  19. Methaemoglobinaemia among neonates in a neonatal intensive care unit.

    PubMed

    Hjelt, K; Lund, J T; Scherling, B; Bendixen, S; Lundstrøm, K; Støvring, S; Voldsgaard, P; Linnet, K

    1995-04-01

    After detection of a few clinical cases of methaemoglobinaemia (methb) in our NICU, a prospective clinical study was undertaken to determine the extent of the problem and to identify the causes. Consequently, during the following 8 months all haemoglobin tests included simultaneous measurements of methb on an OSM 3 hemoximeter (Radiometer): 8% (n = 33) of 415 neonates were found to be methb positive (defined as > or = 6% methb). Mean methb was 19% (range 6.5-45.5%). Maximum methb concentrations were found on day 4-31 postpartum (mean 12 days) and the number of days with a positive methb sample ranged from 1 to 18 days (mean 6 days). About 40% of the neonates born at 25-30 weeks of gestation and 60% with a birth weight < 1000 g were methb positive. Also, there was a negative correlation between the size of the methb positive concentration and gestational age (r = -0.38, p = 0.02). Measurements of C-reactive protein and leucocytes, NADH reductase, pH, Cl, nitrate and nitrite were carried out in methb positive patients. The tests were repeated 1 week after cessation of methb. The only significant difference was an increase in NADH reductase at the second measurement. Likewise, a wide range of clinical parameters were registered and they occurred with a higher frequency among the methb positive patients when compared with a methb negative control group matched with regard to gestational age and the closest possible birth weight. The mean birth weight of methb positive patients was 1170 g and that of negative controls 1380 g (p < 0.006).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7795342

  20. Recombinant AAV Vectors for Enhanced Expression of Authentic IgG

    PubMed Central

    Fuchs, Sebastian P.; Martinez-Navio, José M.; Gao, Guangping; Desrosiers, Ronald C.

    2016-01-01

    Adeno-associated virus (AAV) has become a vector of choice for the treatment of a variety of genetic diseases that require safe and long-term delivery of a missing protein. Muscle-directed gene transfer for delivery of protective antibodies against AIDS viruses and other pathogens has been used experimentally in mice and monkeys. Here we examined a number of variations to AAV vector design for the ability to produce authentic immunoglobulin G (IgG) molecules. Expression of rhesus IgG from a single single-stranded AAV (ssAAV) vector (one vector approach) was compared to expression from two self-complementary AAV (scAAV) vectors, one for heavy chain and one for light chain (two vector approach). Both the one vector and the two vector approaches yielded considerable levels of expressed full-length IgG. A number of modifications to the ssAAV expression system were then examined for their ability to increase the efficiency of IgG expression. Inclusion of a furin cleavage sequence with a linker peptide just upstream of the 2A self-cleaving sequence from foot-and-mouth disease virus (F2A) increased IgG expression approximately 2 fold. Inclusion of these sequences also helped to ensure a proper sequence at the C-terminal end of the heavy chain. Inclusion of the post-transcriptional regulatory element from woodchuck hepatitis virus (WPRE) further increased IgG expression 1.5–2.0 fold. IgG1 versions of the two rhesus IgGs that were examined consistently expressed better than the IgG2 forms. In contrast to what has been reported for AAV2-mediated expression of other proteins, introduction of capsid mutations Y445F and Y731F did not increase ssAAV1-mediated expression of IgG as determined by transduction experiments in cell culture. Our findings provide a rational basis for AAV vector design for expression of authentic IgG. PMID:27332822

  1. Critical role of preconceptional immunization for protective and nonpathological specific immunity in murine neonates.

    PubMed

    Uthoff, Heiko; Spenner, Achim; Reckelkamm, Werner; Ahrens, Birgit; Wölk, Guido; Hackler, Rolf; Hardung, Frank; Schaefer, Jürgen; Scheffold, A; Renz, Harald; Herz, Udo

    2003-10-01

    Expression of Th2 immunity against environmental Ags is the hallmark of the allergic phenotype and contrasts with the Th1-like pattern, which is stably expressed in healthy adults throughout life. Epidemiological studies indicate that the prenatal environment plays an important and decisive role in the development of allergy later in life. Since the underlying mechanisms were unclear, an animal model was developed to study the impact of maternal allergy on the development of an allergic immune response in early life. An allergic Th2 response was induced in pregnant mice by sensitization and aerosol allergen exposure. Both, IgG1 and IgG2a, but not IgE, Abs cross the placental barrier. Free allergen also crosses the placental area and was detected in serum and amniotic fluids of neonatal F(1) mice. These F(1) mice demonstrated a suppressed Th1 response, as reflected by lowered frequencies and reduced levels of IFN-gamma production. Development of an IgE response against the same allergen was completely prevented early in life. This effect was mediated by diaplacental transfer of allergen-specific IgG1 Abs. In contrast, allergic sensitization against a different allergen early in life was accelerated in these mice. This effect was mediated by maternal CD4 and OVA-specific Th2 cells induced by allergic sensitization during pregnancy. These data indicate a critical role for maternal T and B cell response in shaping pre- and postnatal maturation of specific immunity to allergens. PMID:14500644

  2. Alterations in carbohydrate composition of serum IgG from patients with rheumatoid arthritis and from pregnant women.

    PubMed

    Pekelharing, J M; Hepp, E; Kamerling, J P; Gerwig, G J; Leijnse, B

    1988-02-01

    The carbohydrate composition of IgG purified from serum of patients with rheumatoid arthritis (RA), pregnant women, and blood donors has been determined by gas-liquid chromatography. Comparison of the results indicates that IgG from patients with RA contains significantly less galactose but more N-acetylglucosamine than normal IgG, whereas the fucose and sialic acid contents are not changed. The carbohydrate content of IgG in RA is reduced. IgG in pregnancy contains more galactose and more sialic acid than normal IgG, whereas fucose, N-acetylglucosamine, and the total carbohydrate content are not changed. These data suggest a temporal compensation of the RA associated undergalactosylation of IgG in female patients with RA during pregnancy, a period during which remission of the disease is often observed. PMID:3355256

  3. Specific IgG for cat allergens in patients with allergic conjunctivitis.

    PubMed

    Miyama, Anri; Mimura, Tatsuya; Noma, Hidetaka; Goto, Mari; Kamei, Yuko; Kondo, Aki; Saito, Yusuke; Okuma, Hiroko; Matsubara, Masao

    2015-08-01

    Immunoglobulin G (IgG) antibodies are involved in type II and type III hypersensitivity. We evaluated the relation between perennial allergic conjunctivitis and serum levels of specific IgG for cat allergens. A prospective study was conducted in patients with seasonal allergic conjunctivitis (seasonal group, n = 10), patients with perennial allergic conjunctivitis (perennial group, n = 10), and healthy control subjects (control group, n = 10). Serum levels of specific IgE and IgG for cat allergens and total tear IgE were measured, and a skin prick test was also performed. In addition, a severity score associated with allergic conjunctivitis was calculated (0-30). The positive rates and scores of for total tear IgE, serum cat-specific IgE, and serum cat-specific IgG were all higher in the seasonal and perennial groups than in the control group (all p < 0.05). Serum cat-specific IgG levels were higher in the perennial group than in the seasonal group (p = 0.0156), but there was no significant difference in the grade of cat-specific IgE between the two groups (p = 0.3008). On multivariate analysis, the mean wheal diameter for cat allergen was associated with the serum level of cat-specific IgG (not IgE) in all patients [odds ratio (OR) = 31.979, p < 0.0001]. Multivariate analysis revealed that the total objective score was strongly associated with serum cat-specific IgG (OR = 23.015, p < 0.0001). These findings suggest that specific IgG antibodies may be involved in perennial allergic symptoms caused by indoor allergens such as cat allergens. PMID:25189683

  4. Rituximab for the treatment of IgG4-related orbital disease: experience from five cases

    PubMed Central

    Wu, A; Andrew, N H; Tsirbas, A; Tan, P; Gajdatsy, A; Selva, D

    2015-01-01

    Purpose To review the clinical efficacy and safety of rituximab for treatment of IgG4-related orbital disease (IgG4-ROD). Design Retrospective multicentre interventional case series. Methods Chart review for five cases of biopsy-confirmed IgG4-ROD (IgG4+>10/HPF, ratio of IgG4+/IgG+>40%) treated with rituximab. Information retrieved included the dosing schedule, adverse events and the magnitude, temporality, and duration of the clinical response. Results All cases of IgG4-ROD were either steroid dependent or steroid resistant. Rituximab doses for induction therapy included two doses of 1000 mg at 2-weekly intervals, and four doses at 375 mg/m2 at weekly intervals. Two months after starting rituximab, three cases achieved complete clinical resolution and two cases achieved partial clinical resolution. Complete radiological resolution occurred in one case, and partial radiological resolution in three cases. Three cases received rituximab maintenance therapy and one case was commenced on mycophenolate. No relapse occurred during a mean follow-up of 33 months (range: 7–65 months). One disease relapse occurred when the dosing interval of rituximab maintenance therapy was extended to 6–monthly intervals; remission was swiftly achieved with rituximab reinduction therapy. The only adverse effects reported were one episode of fatigue lasting 1 week and two episodes of orbital discomfort. Conclusion Rituximab may be an effective treatment option for IgG4-ROD that is steroid dependent or steroid intolerant. Rituximab therapy resulted in swift clinical and radiological improvement, many months free of relapse, and few side effects. PMID:25341435

  5. Rituximab for the Treatment of IgG4-Related Tubulointerstitial Nephritis

    PubMed Central

    McMahon, Blaithin A.; Novick, Tessa; Scheel, Paul J.; Bagnasco, Serena; Atta, Mohamed G.

    2015-01-01

    Abstract Immunoglobulin type gamma 4 (IgG4)-related disease is a relatively newly described clinical entity characterized by a distinctive histopathological appearance, increased numbers of IgG4 positive plasma cells and often, but not always, elevated serum IgG4 concentrations. The most common renal manifestation of IgG4-related disease is tubulointerstitial nephritis marked with proteinuria, hematuria, decreased kidney function, hypocomplementemia, and radiologic abnormalities. Renal biopsy characteristics include dense lymphoplasmacytic tubulointerstitial nephritis that stains for IgG4, storiform fibrosis, and immune complex deposition in the interstitium and along tubule basement membranes. Treatment traditionally consists of prolonged glucocorticoids but cases refractory to glucocorticoids have been reported. We report a case of a 58-year-old Caucasian man who presented with fatigue, 50 pound weight loss, dyspnea, lymphadenopathy, and nephromegaly. The patient was first misdiagnosed as chronic interstitial nephritis secondary to renal sarcoid and was treated with repeated doses of prednisone. On his third relapse, he underwent a repeat renal biopsy and a diagnosis of IgG4-tubulointerstitial nephritis was confirmed. He was refractory to treatment with prednisone. The patient received Rituximab and had prompt sustained improvement in renal function. At 1 year post Rituximab treatment, his serum creatinine remains at baseline and imaging study revealed reduction in his kidney size. This is the first case report using Rituximab as a steroid sparing option for refractory IgG4-tubulointerstitial nephritis. More information is needed on the long-term effects of using of B-cell depleting agents for glucocorticoid resistant IgG4-tubulointerstitial nephritis. PMID:26266393

  6. Hypercatabolism of normal IgG; an unexplained immunoglobulin abnormality in the connective tissue diseases

    PubMed Central

    Wochner, R. Dean

    1970-01-01

    The metabolism of radioiodinated IgG was studied in a series of 42 patients with connective tissue diseases (16 systemic lupus erythematosus, nine rheumatoid arthritis, five polymyositis, five vasculitis, and seven miscellaneous diagnoses). Fractional catabolic rates were increased and survival half-lives were shortened in all diagnostic categories indicating hypercatabolism of IgG. This hypercatabolism was masked by increased IgG synthesis, resulting in elevated serum concentrations of IgG in patients with systemic lupus erythematosus and rheumatoid arthritis and in generally normal concentrations in the others. The metabolism of iodinated IgM was also studied in eight patients with systemic lupus erythematosus, in seven with rheumatoid arthritis, and in 12 controls. The fractional catabolic rates were normal in both groups of patients. Serum concentrations of both IgM and IgA were moderately elevated in all diagnostic categories. Serum albumin metabolism was entirely normal in the nine subjects studied who were not receiving corticosteroids; in three who were receiving them, moderate hypercatabolism was observed. The hypercatabolism of IgG could not be accounted for by factors previously known to alter IgG metabolism. It was not observed in 15 patients with other chronic, inflammatory diseases and was not explained by concomitant administration of adrenal corticosteroids to some patients. Identical results were obtained whether the IgG was obtained from a patient himself or from a normal donor, demonstrating that the hypercatabolism is a host defect and not an abnormality of the protein. Thus, patients with connective tissue disease of several different diagnostic categories have been shown to have an unexplained immunoglobulin abnormality: they catabolize normal IgG at an accelerated rate. PMID:5415673

  7. Increased in vivo effector function of human IgG4 isotype antibodies through afucosylation.

    PubMed

    Gong, Qian; Hazen, Meredith; Marshall, Brett; Crowell, Susan R; Ou, Qinglin; Wong, Athena W; Phung, Wilson; Vernes, Jean-Michel; Meng, Y Gloria; Tejada, Max; Andersen, Dana; Kelley, Robert F

    2016-01-01

    For some antibodies intended for use as human therapeutics, reduced effector function is desired to avoid toxicities that might be associated with depletion of target cells. Since effector function(s), including antibody-dependent cell-mediated cytotoxicity (ADCC), require the Fc portion to be glycosylated, reduced ADCC activity antibodies can be obtained through aglycosylation of the human IgG1 isotype. An alternative is to switch to an IgG4 isotype in which the glycosylated antibody is known to have reduced effector function relative to glycosylated IgG1 antibody. ADCC activity of glycosylated IgG1 antibodies is sensitive to the fucosylation status of the Fc glycan, with both in vitro and in vivo ADCC activity increased upon fucose removal ("afucosylation"). The effect of afucosylation on activity of IgG4 antibodies is less well characterized, but it has been shown to increase the in vitro ADCC activity of an anti-CD20 antibody. Here, we show that both in vitro and in vivo activity of anti-CD20 IgG4 isotype antibodies is increased via afucosylation. Using blends of material made in Chinese hamster ovary (CHO) and Fut8KO-CHO cells, we show that ADCC activity of an IgG4 version of an anti-human CD20 antibody is directly proportional to the fucose content. In mice transgenic for human FcγRIIIa, afucosylation of an IgG4 anti-mouse CD20 antibody increases the B cell depletion activity to a level approaching that of the mIgG2a antibody. PMID:27216702

  8. Effects of Bordetella pertussis components on IgE and IgG1 responses.

    PubMed

    Sekiya, K

    1983-01-01

    The effect of dermonecrotic toxin (DNT), fimbrial hemagglutinin (FHA), K-agglutinogen, lipopolysaccharide (LPS), and pertussigen from Bordetella pertussis on the production of IgE and IgG1 antibodies to hen egg albumin (Ea) was investigated in C57BL/6 mice. The IgE antibody contents were determined by passive cutaneous anaphylaxis (PCA) in the skin of Lewis rats, while the IgG1 antibody contents were determined by PCA reactions on the skin of mice using sera that had been heated for 3 hr at 56 C to destroy the IgE antibodies. Among the B. pertussis components tested, pertussigen was the most effective adjuvant for increasing the IgE and IgG1 antibodies to Ea. LPS also moderately increased both types of antibodies, and FHA slightly increased the IgG1 titers. When LPS was given 5 days before Ea, it suppressed both IgE and IgG1 titers while FHA had only slight adjuvant action on both type of antibodies. When each of the components was tested for its ability to modify the adjuvant action of pertussigen, it was found that only DNT interfered significantly with the adjuvanticity of pertussigen when given on the day of immunization with Ea. When the components were given 5 days before Ea, DNT produced significant suppression of only the IgG1 response. LPS, FHA, and K-agglutinogen did not significantly affect the adjuvant action of pertussigen. PMID:6321910

  9. Colovesical fistula caused by glucocorticoid therapy for IgG4-related intrapelvic mass.

    PubMed

    Yabuuchi, Yohei; Matsubayashi, Hiroyuki; Matsuzaki, Masato; Shiomi, Akio; Moriguchi, Michihisa; Kawamura, Ichiro; Ito, Ichiro; Ono, Hiroyuki

    2015-12-16

    IgG4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory disorder that can occur in almost all systemic organs and generally responds to corticosteroid treatment. We report a rare case of an IgG4-related intrapelvic mass lesion that responded to steroid therapy but caused a fistula between the sigmoid colon and bladder. A 71-year-old man was followed after treatment for hepatocellular carcinoma. Follow-up computed tomography (CT) incidentally depicted left hydronephrosis with an ill-demarcated intrapelvic mass lesion. This lesion was histologically diagnosed as IgG4-RD by open biopsy, and peroral steroid therapy was initiated. One month after starting steroids, a colovesical fistula was detected by follow-up CT. A colostomy and urethral catheterization were emergently performed. The patient recovered and the mass lesion was drastically minimized by the initiation of glucocorticoids; however, he still needs urethral catheterization. IgG4-RD develops in various systemic organs and generally responds well to steroids. Clinicians must be watchful for the complications of responses to corticosteroids, such as fistulization, when the mass lesion of IgG4-RD is adjacent to multiple luminal organs. PMID:26677450

  10. Elbow- and hinge-bending motions of IgG: Dielectric response and dynamic feature.

    PubMed

    Hayashi, Yoshihito; Yagihara, Shin

    2016-09-01

    Immunoglobulin G (IgG) is a Y-shaped globular protein consisting of two Fab segments connecting to an Fc segment with a flexible hinge region, in which the Fab segments show secondary flexibility at an "elbow" region. In the present work, the hinge-bending and elbow-bending motions of aqueous solutions of IgG by microwave dielectric measurements below the freezing point of bulk water was observed. The presence of unfreezable water around the macromolecules reduced the effects of steric hindrance normally generated by ice and enabled the intramolecular motions of IgG. At the same time, the overall IgG molecule rotation was restricted by ice. Papain digestion and reduction of the disulfide linkage at the hinge region was used to generate Fab and Fc fragments. In solutions of these fragments, the dielectric relaxation process of the hinge-bending motion was absent, although the elbow-bending motion remained. Three relaxation processes were observed for papain-digested IgG. The high, middle, and low frequency processes were attributed to unfrozen water, local peptide motions cooperating with bound water, and the elbow-bending motion, respectively. In the case of the intact IgG, an additional relaxation process due to the hinge-bending motion was observed at frequencies lower than that of the elbow-bending motion. © 2016 Wiley Periodicals, Inc. Biopolymers 105: 626-632, 2016. PMID:27018805

  11. IgG4-related renal disease: clinical and pathological characteristics.

    PubMed

    Kuroda, Naoto; Nao, Tomoya; Fukuhara, Hideo; Karashima, Takashi; Inoue, Keiji; Taniguchi, Yoshinori; Takeuchi, Mai; Zen, Yoh; Sato, Yasuharu; Notohara, Kenji; Yoshino, Tadashi

    2014-01-01

    IgG4-related disease is a recently established systemic condition. Tubulointerstitial nephritis is the most common renal manifestation. Glomerular lesions, particularly membranous glomerulonephritis, can develop simultaneously. Some patients present with serological renal dysfunction associated with elevated IgG or IgE levels and hypocomplementemia, while others are incidentally found to have abnormalities in kidneys on imaging. A majority of patients with IgG4-related kidney disease have similar lesions at other anatomical sites, which help us to suspect this condition. Serum IgG4 elevation (>135 mg/dL) is the most, although not entirely, specific marker for the diagnosis. Imaging findings varies from small nodules to bilateral diffuse abnormalities. In addition to the renal parenchyma, the renal pelvis and perirenal adipose tissue can be affected. Histological features include dense lymphoplasmacytic infiltration, storiform or "bird's eye" fibrosis (highlighted by PAM stain), and IgG4-positive plasma cell infiltration (>10 cells/high-power field and IgG4/IgG-positive cell ratio >40%). Immune complex deposition is detectable in the tubular basement membrane by immunofluorescence and/or electron microscopy. Patients usually respond well to corticosteroids, but highly active diseases may require other immunosuppressive therapies. Further investigations will be required to fully understand pathophysiology underlying this emerging condition. PMID:25337295

  12. Distribution of nominal and latent IgG (Gm) allotypes in plaques of multiple sclerosis brain.

    PubMed Central

    Salier, J P; Glynn, P; Goust, J M; Cuzner, M L

    1983-01-01

    Concentrations of IgG allotypes G1m(1), G1m(3) and G3m(11) in neutral pH eluates from discrete plaques of multiple sclerosis (MS) brain and from white matter of control brain were determined to obtain information about distribution of B cell clones among MS lesions. Within each MS brain a predominant nominal IgG1 allotype was distributed rather homogeneously in all plaques while quantitatively minor allotypes showed some fluctuation. Latent IgG1 allotypes were detected (7-12% of the corresponding nominal allotype level) in some tissue eluates from both MS and control brains, which were homozygous for either G1m(1) or G1m(3). By contrast, the expression of a latent IgG3 allotype, namely G3m(11), was apparently MS restricted. Large amounts of latent allotypes were detected only in recent plaques with lymphoid cells whereas the distribution of total plaque associated IgGs did not correlate with the presence of lymphoid cells. Latent allotypes in recent MS lesions may mark a transient immunological activity which coincides with the infiltration of lymphoid cells and precedes the appearance in these plaques of oligoclonal IgGs, the distribution of which may parallel that of the predominant nominal allotypes. PMID:6606512

  13. Distribution of nominal and latent IgG (Gm) allotypes in plaques of multiple sclerosis brain.

    PubMed

    Salier, J P; Glynn, P; Goust, J M; Cuzner, M L

    1983-12-01

    Concentrations of IgG allotypes G1m(1), G1m(3) and G3m(11) in neutral pH eluates from discrete plaques of multiple sclerosis (MS) brain and from white matter of control brain were determined to obtain information about distribution of B cell clones among MS lesions. Within each MS brain a predominant nominal IgG1 allotype was distributed rather homogeneously in all plaques while quantitatively minor allotypes showed some fluctuation. Latent IgG1 allotypes were detected (7-12% of the corresponding nominal allotype level) in some tissue eluates from both MS and control brains, which were homozygous for either G1m(1) or G1m(3). By contrast, the expression of a latent IgG3 allotype, namely G3m(11), was apparently MS restricted. Large amounts of latent allotypes were detected only in recent plaques with lymphoid cells whereas the distribution of total plaque associated IgGs did not correlate with the presence of lymphoid cells. Latent allotypes in recent MS lesions may mark a transient immunological activity which coincides with the infiltration of lymphoid cells and precedes the appearance in these plaques of oligoclonal IgGs, the distribution of which may parallel that of the predominant nominal allotypes. PMID:6606512

  14. Enhancement of anti-OVA IgG2c production in vivo by enalapril

    PubMed Central

    Almeida, L.C.; Muraro, L.S.; Albuquerque, D.A.

    2016-01-01

    Angiotensin-converting enzyme (ACE) inhibitors have non-hemodynamic, pleiotropic effects on the immune response. The effects of ACE inhibitors on the production of cytokines and T-cell functions are well established. However, little is known on the effects of these medicines on humoral response to foreign antigens. In this study, we investigated the effect of enalapril treatment on ovalbumin (OVA)-specific IgG1 and IgG2c production in mice determined by ELISA. Two groups of 8-week-old C57BL/6 females mice (3–4/group) were subcutaneously immunized with OVA (10 μg/animal) in presence of Alhydrogel (1 mg/mouse) and boosted at day 21. The mice were treated with enalapril (5 mg/kg daily, po) or were left without treatment for one month. The animals were bled from the orbital plexus on days 0, 7, 14, 21, and 28 after the first immunization and the sera were stored at –20°C until usage. OVA-specific serum IgG1 and IgG2c were determined by ELISA using serum from each individual animal. The results showed that enalapril significantly increased anti-OVA serum IgG2c in the secondary response without affecting IgG1 synthesis. These data expand our understanding on the properties of enalapril on the immune response, including antibody production. PMID:27409332

  15. Enhancement of anti-OVA IgG2c production in vivo by enalapril.

    PubMed

    Almeida, L C; Muraro, L S; Albuquerque, D A

    2016-07-11

    Angiotensin-converting enzyme (ACE) inhibitors have non-hemodynamic, pleiotropic effects on the immune response. The effects of ACE inhibitors on the production of cytokines and T-cell functions are well established. However, little is known on the effects of these medicines on humoral response to foreign antigens. In this study, we investigated the effect of enalapril treatment on ovalbumin (OVA)-specific IgG1 and IgG2c production in mice determined by ELISA. Two groups of 8-week-old C57BL/6 females mice (3-4/group) were subcutaneously immunized with OVA (10 μg/animal) in presence of Alhydrogel (1 mg/mouse) and boosted at day 21. The mice were treated with enalapril (5 mg/kg daily, po) or were left without treatment for one month. The animals were bled from the orbital plexus on days 0, 7, 14, 21, and 28 after the first immunization and the sera were stored at -20°C until usage. OVA-specific serum IgG1 and IgG2c were determined by ELISA using serum from each individual animal. The results showed that enalapril significantly increased anti-OVA serum IgG2c in the secondary response without affecting IgG1 synthesis. These data expand our understanding on the properties of enalapril on the immune response, including antibody production. PMID:27409332

  16. The Pathology of IgG4-Related Disease in the Bile Duct and Pancreas.

    PubMed

    Zen, Yoh

    2016-08-01

    Immunoglobulin G4-related disease (IgG4-RD) in the pancreatobiliary system manifests as sclerosing cholangitis (SC), hepatic inflammatory pseudotumors, and type 1 autoimmune pancreatitis (AIP). The pathology of IgG4-RD involves an inflammatory process and fibrogenic pathway, the combination of which damages the affected organs. Fibroinflammatory injury is characterized by three microscopic findings: a diffuse lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, obliterative phlebitis, and storiform fibrosis. Although the diagnosis of IgG4-related pancreatocholangitis is relatively straightforward in surgical specimens, the current clinical requirement is to diagnose patients using biopsy samples, which remains challenging. Histological differential diagnoses include primary SC, follicular cholangitis/pancreatitis, SC with granulocytic epithelial lesions, and type 2 AIP. Although the massive infiltration of IgG4-positive plasma cells is a histological hallmark of IgG4-RD, many other immune cells (e.g., Th2 lymphocytes, regulatory T cells, and M2 macrophages) appear to be strongly involved in orchestral immune reactions. PMID:27466794

  17. IgG4-related disease manifesting as an acute gastric-pericardial fistula.

    PubMed

    Frydman, James; Grunner, Shahar; Kluger, Yoram

    2014-11-28

    IgG4-related disease is a recently recognized entity linked initially to autoimmune pancreatitis and has been subsequently described in nearly every organ system. Men over the age of 50 represent the most affected demographic group and a comprehensive set of diagnostic criteria has been developed to aid treating clinicians. Though elevated levels of IgG4 in the serum are suggestive of the disease, definitive diagnosis is made on histopathology. Treatment is tailored to the clinical presentation with corticosteroid therapy known to have proven efficacy. Gastric manifestations of the IgG4-related disease primarily come in two varieties, notably chronic ulceration or pseudotumor formation. Autoimmune pancreatitis conveys increased risk for IgG4-related disease of the stomach, which is independent of Helicobacter pylori status. In this case report, we present an acute gastric-pericardial fistula secondary to IgG4-related disease that required urgent operative management. To our knowledge, this is the first report in the medical literature describing this complication of IgG4-related disease. PMID:25469052

  18. IgG4-related disease manifesting as an acute gastric-pericardial fistula

    PubMed Central

    Frydman, James; Grunner, Shahar; Kluger, Yoram

    2014-01-01

    IgG4-related disease is a recently recognized entity linked initially to autoimmune pancreatitis and has been subsequently described in nearly every organ system. Men over the age of 50 represent the most affected demographic group and a comprehensive set of diagnostic criteria has been developed to aid treating clinicians. Though elevated levels of IgG4 in the serum are suggestive of the disease, definitive diagnosis is made on histopathology. Treatment is tailored to the clinical presentation with corticosteroid therapy known to have proven efficacy. Gastric manifestations of the IgG4-related disease primarily come in two varieties, notably chronic ulceration or pseudotumor formation. Autoimmune pancreatitis conveys increased risk for IgG4-related disease of the stomach, which is independent of Helicobacter pylori status. In this case report, we present an acute gastric-pericardial fistula secondary to IgG4-related disease that required urgent operative management. To our knowledge, this is the first report in the medical literature describing this complication of IgG4-related disease. PMID:25469052

  19. Optimizing IgG therapy in chronic autoimmune neuropathies: a hypothesis driven approach.

    PubMed

    Berger, Melvin; Allen, Jeffrey A

    2015-03-01

    Prolonged intravenous immunoglobulin (IVIG) therapy is used for the chronic autoimmune neuropathies chronic idiopathic demyelinating polyneuropathy and multifocal motor neuropathy, but the doses and treatment intervals are usually chosen empirically due to a paucity of data from dose-response studies. Recent studies of the electrophysiology and immunology of these diseases suggest that antibody-induced reversible dysfunction of nodes of Ranvier may play a role in conduction block and disability which responds to immunotherapy more rapidly than would be expected for demyelination or axonal damage per se. Clinical reports suggest that in some cases, the effects of each dose of IVIG may be transient, wearing-off before the next dose is due. These observations lead us to hypothesize that that therapeutic IgG acts by competing with pathologic autoantibodies and that individual patients may require different IgG levels for optimal therapeutic effects. Frequent IVIG dosing and weekly subcutaneous IgG have been tried as ways of continuously maintaining high serum IgG levels, resulting in stabilization of neuromuscular function in small case series. Frequent grip strength and disability measurements, performed by the patient at home and reported electronically, can be used to assess the extent and duration of responses to IgG doses. Individualization of IgG treatment regimens may optimize efficacy, minimize disability, and identify nonresponders. PMID:25418426

  20. Detergent induces the formation of IgG aggregates: a multi-methodological approach.

    PubMed

    Amani, Samreen; Nasim, Faisal; Khan, Taqi Ahmed; Fazili, Naveed Ahmad; Furkan, Mohammad; Bhat, Imtiyaz Ahmad; Khan, Javed Masood; Khan, Rizwan Hasan; Naeem, Aabgeena

    2014-01-01

    Role of micellar environment created by Triton X-100 (TX-100) and CHAPSO on protein conformation using IgG as a model system has been studied in this paper. A substantial amount of secondary structure with the reduction in constant tertiary contacts was obtained in both bovine and human IgG in the presence of 0.12 mM TX-100 where as 6 and 8 mM CHAPSO concentration was required for this type of secondary structure. Further addition of either of the detergents result in the induction of α-helix in both the IgGs as evident by helix specific peaks in the amide I region of FTIR and circular dichroism spectra. Tryptophan and 8-anilino-1-naphthalene-sulphonic acid (ANS) fluorescence confirmed changes in protein conformation upon addition of detergents. Maximum ANS binding at 0.12 mM TX-100 in both while 6 and 8 mM CHAPSO in bovine and human IgG respectively, indicate a compact ''molten-globule''-like conformation. An increase addition of these detergents results in the burial of hydrophobic patches of both IgG owing to aggregation. Presence of aggregates at 0.2 and 0.16 mM TX-100 and 8 and 9 mM CHAPSO, for bovine and human IgG respectively, was further confirmed by reduction in ANS fluorescence, dynamic light scattering study, thioflavin T fluorescence and congo red absorbance. PMID:24184618

  1. Serum IgG antibodies to C1q in hypocomplementemic urticarial vasculitis syndrome.

    PubMed

    Wisnieski, J J; Naff, G B

    1989-09-01

    Urticaria, angioedema, and arthritis are cardinal features of hypocomplementemic urticarial vasculitis syndrome (HUVS). Considered to be an immune complex-mediated disorder, HUVS has been differentiated from systemic lupus erythematosus (SLE), based on its clinical manifestations and the C1q precipitin (C1q-p) reaction, which is manifested as gel precipitation of C1q by a small percentage of HUVS IgG molecules. This phenomenon has been attributed to an Fc region abnormality, and the responsible IgG molecules are said to possess C1q-p activity. We purified IgG from 4 HUVS patients and confirmed that HUVS IgG contains C1q binding activity. F(ab')2 fragments from these patients also bound to C1q, as measured by 2 different C1q binding methods at physiologic ionic strength; HUVS IgG Fc fragments did not bind to C1q. Preincubation of HUVS F(ab')2 fragments with antibody to human F(ab')2 prevented subsequent binding to C1q. We conclude that IgG antibodies to C1q are present in HUVS serum, and it is likely that these antibodies are C1q-p. Because the clinical manifestations of HUVS and the presence of anti-C1q antibodies have been described in patients with SLE, our findings support the concept that HUVS is an autoimmune syndrome related to SLE. PMID:2528353

  2. Autoimmunoreactive IgGs Against Cardiac Lipid Raft-Associated Proteins in Patients with POTS

    PubMed Central

    Wang, Xiao-Li; Ling, Tian-You; Charlesworth, M. Cristine; Figueroa, Juan J.; Low, Phillip; Shen, Win-Kuang; Lee, Hon-Chi

    2013-01-01

    Lipid rafts are specialized plasma membrane microdomains that serve as platforms for integrating cellular signal transductions. We have recently reported that autoantibodies against cardiac membrane proteins are present in patients with postural orthostatic tachycardia syndrome (POTS). In this study, we examined the presence of autoimmunoreactive IgGs against lipid raft proteins in these patients. IgGs were purified from the sera of 10 patients and 7 normal controls. Cardiac lipid raft preparations were isolated from normal human heart tissue. The lipid raft-associated proteins were resolved by 2DE and immunoblotted against IgGs from each subject. Protein spots that reacted specifically with patient IgGs were identified by nanoLC-MS/MS. Thirty-four such protein spots, and 72 unique proteins were identified. The targets of autoimmunoreactive IgGs include proteins associated with caveolae structure, adrenergic signaling, calcium signaling, cytostructures, chaperone and energy metabolism. Multiple pathways were involved including those that regulate caveolae-mediated signaling, oxidative phosphorylation, fatty acid metabolism, protein ubiquitination, and cardiac β-adrenergic signaling. Our results suggest that cardiac lipid raft-associated proteins are targets of autoimmunoreactive IgGs from patients with POTS. Autoimmunity may play a role in the pathogenesis of POTS. PMID:23562385

  3. Dose-dependent platelet stimulation and inhibition induced by anti-PIA1 IgG

    SciTech Connect

    Ryu, T.; Davis, J.M.; Schwartz, K.A. )

    1990-07-01

    The PIA1 antibody produces several clinically distinct and severe thrombocytopenias. Investigations have demonstrated divergent effects on platelet function; prior reports demonstrated inhibition, while a conflicting publication showed platelet activation. We have resolved this conflict using anti-PIA1 IgG produced by a patient with posttransfusion purpura. Relatively low concentrations stimulated platelet aggregation and release of adenosine triphosphate (ATP) whereas high concentrations inhibited platelet function, producing a thrombasthenia-like state. The number of molecules of platelet-associated IgG necessary to initiate aggregation and ATP release (2,086 +/- 556) or produce maximum aggregation (23,420 +/- 3,706) or complete inhibition (63,582 +/- 2654) were measured with a quantitative radiometric assay for bound anti-PIA1. Preincubation of platelets with high concentrations of PIA1 antibody inhibited platelet aggregation with 10 mumol/L adenosine diphosphate and blocked 125I-labeled fibrinogen platelet binding. Platelet activation with nonfibrinogen dependent agonist, 1 U/ml thrombin, was not inhibited by this high concentration of PIA1 IgG. In conclusion, anti-PIAI IgG produces (1) stimulation of platelet aggregation and ATP release that is initiated with 2000 molecules IgG per platelet and is associated with an increase of 125I-fibrinogen binding; (2) conversely, inhibition of platelet aggregation is observed with maximum antibody binding, 63,000 molecules IgG per platelet, and is mediated via a blockade of fibrinogen binding.

  4. Antiradiation Antitoxin IgG : Immunological neutralization of Radiation Toxins at Acute Radiation Syndromes.

    NASA Astrophysics Data System (ADS)

    Popov, Dmitri; Maliev, Slava

    Introduction: High doses of radiation induce apoptotic necrosis of radio-sensitive cells. Mild doses of radiation induce apoptosis or controlled programmed death of radio-sensitive cells with-out development of inflammation and formation of Radiation Toxins. Cell apoptotic necrosis initiates Radiation Toxins (RT)formation. Radiation Toxins play an important role as a trig-ger mechanism for inflammation development and cell lysis. If an immunotherapy approach to treatment of the acute radiation syndromes (ARS) were to be developed, a consideration could be given to neutralization of radiation toxins (Specific Radiation Determinants-SRD) by specific antiradiation antibodies. Therapeutic neutralization effects of the blocking anti-radiation antibodies on the circulated RT had been studied. Radiation Toxins were isolated from the central lymph of irradiated animals with Cerebrovascular(Cv ARS),Cardiovascular (Cr ARS),Gastrointestinal(Gi ARS) and Haemopoietic (Hp ARS) forms of ARS. To accomplish this objective, irradiated animals were injected with a preparation of anti-radiation immunoglobulin G (IgG) obtained from hyperimmune donors. Radiation-induced toxins that we call Specific Radiation Determinants (SRD) possess toxic (neurotoxic, haemotoxic) characteristics as well as specific antigenic properties. Depending on direct physiochemical radiation damage, they can induce development of many of the pathological processes associated with ARS. We have tested several specific hyperimmune IgG preparations against these radiation toxins and ob-served that their toxic properties were neutralized by the specific antiradiation IgGs. Material and Methods: A scheme of experiments was following: 1.Isolation of radiation toxins (RT) from the central lymph of irradiated animals with different form of ARS. 2.Transformation of a toxic form of the RT to a toxoid form of the RT. 3.Immunization of radiation naive animals. Four groups of rabbits were inoculated with a toxoid form of SRD

  5. Neonatal medicine in ancient art.

    PubMed

    Yurdakök, Murat

    2010-01-01

    There are a limited number of artistic objects from ancient times with particular importance in neonatal medicine. The best examples are figurines from ancient Egypt of Isis nursing Horus, showing the importance of breastfeeding. The earliest images of the human fetus were made by the Olmecs in Mexico around 1200- 400 BCE. One of the earliest representations of congenital anomalies is a figurine of diencephalic twins thought to be the goddess of Anatolia, dated to around 6500 BCE. In addition to these figurines, three sets of twins in the ancient world have medical importance, and Renaissance artists often used them as a subject for their paintings: "direct suckling animals" (Romulus and Remus), "heteropaternal superfecundation" (mother: Leda, fathers: Zeus, the king of the Olympian gods, and Leda's husband, Tyndareus), and "twin-to-twin transfusion" in monozygotic twins (Jacob and Esau). PMID:20560265

  6. Futile care and the neonate.

    PubMed

    Romesberg, Tricia L

    2003-10-01

    The concept of futile care is controversial and difficult to define. Efforts to prolong life, once considered an outcome of healing, may now be viewed by some as harmful acts of prolonging suffering. This article reviews a number of cases representing this challenging ethical dilemma, such as Baby K and MacDonald v. Milleville. The Baby Doe regulations, the Emergency Medical Treatment and Labor Act (EMTALA), and the Born-Alive Protection Act of 2001, also are discussed to provide an improved understanding of the legal framework that impacts ethical decision making. Nurses at the bedside must be equipped with the ethical knowledge and communication skills necessary to care for patients and families facing the ethical dilemma of futile care. An increased focus on neonatal palliative care is suggested to provide infants, families, and staff with the necessary tools to work through this painful process. PMID:14648518

  7. Neonatal thyroid-stimulating hormone level is influenced by neonatal, maternal, and pregnancy factors.

    PubMed

    Trumpff, Caroline; Vandevijvere, Stefanie; Moreno-Reyes, Rodrigo; Vanderpas, Jean; Tafforeau, Jean; Van Oyen, Herman; De Schepper, Jean

    2015-11-01

    The percentage of newborns with a neonatal whole blood thyroid-stimulating hormone (TSH) greater than 5 mIU/L has been used as an indicator of iodine deficiency at the population level. However, TSH levels in newborns may be influenced by many factors other than iodine status. The objective of this study was to identify neonatal, maternal, and pregnancy-related determinants of neonatal TSH levels in a retrospective cohort study. The study sample included 313 Belgian mothers and their 4- to 5-year-old children. The children had a neonatal TSH concentration between 0 and 15 mIU/L at neonatal screening, and blood samples were collected 3 to 5 days after birth. Children with suspected congenital hypothyroidism (neonatal TSH level >15 mIU/L), prematurely born (i.e., <37 weeks), or with a low birth weight (i.e., <2500 g) were excluded. Information about maternal and birth-related determinants was collected from the neonatal screening center via a self-administered questionnaire filled in by the mother together with the child's health booklet. Higher TSH levels were found in spring and winter compared to summer and autumn (P = .011). Higher TSH levels were associated with lifetime smoking behavior (up to child birth) in the mother (P = .005), lower weight gain during pregnancy (P = .014), and longer pregnancies (P = .003). This study showed that several neonatal, maternal, and pregnancy-related determinants are influencing neonatal TSH level. PMID:26428622

  8. Expression of murine Fc receptors for IgG.

    PubMed

    Schreiber, R E; Buku, A; Unkeless, J C

    1990-06-15

    There are two distinct genes that encode murine low affinity Fc gamma RII, murine Fc gamma RII alpha, and murine Fc gamma RII beta, which are transcribed in specific cell lineages. Fc gamma RII alpha transcripts are present in macrophages, NK cells, and mesangial cells; Fc gamma RII beta transcripts are expressed in Fc gamma R-bearing B cells, T cells, and macrophages. We have devised a sandwich ELISA to quantify the expression of Fc gamma RII alpha protein. The ELISA is specific for Fc gamma RII alpha, and does not detect the closely related Fc gamma RII beta protein. Upon stimulation with IFN-gamma the Fc gamma RII beta- macrophage cell line J774a expressed a twelvefold enhanced level of Fc gamma RII alpha protein. Peritoneal macrophages synthesized varying amounts of Fc gamma RII alpha. High levels of Fc gamma RII alpha were observed in resident and thioglycollate-elicited peritoneal macrophages, but no Fc gamma RII alpha was detected in Bacillus Calmette Guérin-elicited macrophages. J774a cells stimulated with rIL-6 bound approximately twice as much anti-Fc gamma RII mAb 2.4G2 IgG as did unstimulated controls. However, the Fc gamma RII alpha-specific ELISA showed no change in the amount of Fc gamma RII alpha expressed. A probe encompassing the extracellular coding sequence of Fc gamma RII beta hybridized to two distinct transcripts that were elevated in rIL-6-stimulated J774a cells. One of these transcripts had the same mobility in electrophoresis as Fc gamma RII alpha mRNA and hybridized to an Fc gamma RII alpha-specific probe, whereas the other transcript was larger and did not hybridize to probes specific for either Fc gamma RII alpha or Fc gamma RII beta. Moreover, we confirmed, with an Fc gamma RII beta-specific probe, that J774a cells do not make Fc gamma RII beta mRNA. Thus, the larger transcript appears to encode a novel Fc gamma RII. We suggest that the increased level of binding of the anti-Fc gamma RII mAb 2.4G2 to rIL-6-induced cells represents

  9. Transient neonatal hyperthyrotrophinaemia: a serum abnormality due to transplacentally acquired antibody to thyroid stimulating hormone.

    PubMed Central

    Lazarus, J H; John, R; Ginsberg, J; Hughes, I A; Shewring, G; Smith, B R; Woodhead, J S; Hall, R

    1983-01-01

    In a screening programme for neonatal hypothyroidism an otherwise healthy female infant was found to have a high concentration of thyroid stimulating hormone in a filter paper blood spot and in serum. A high concentration was also found in the maternal serum. Mother and baby were both biochemically euthyroid with normal serum thyroxine concentrations. The apparently high concentration of thyroid stimulating hormone in the mother was due to the presence of an IgG antibody that bound to human but not bovine thyroid stimulating hormone. Maternal serum inhibited the action of human thyroid stimulating hormone in an in vitro bioassay for the hormone. It is suggested that the baby acquired the antibody transplacentally, especially as the concentration of thyroid stimulating hormone subsequently fell. It is concluded that maternal serum should be assayed for thyroid stimulating hormone when a neonate is found to have a high concentration of the hormone and a normal concentration of thyroxine to establish the incidence of this finding and to avoid inappropriate replacement treatment. PMID:6402161

  10. Whole blood viscosity of preterm infants - differences to term neonates.

    PubMed

    Kuss, N; Bauknecht, E; Felbinger, C; Gehm, J; Gehm, L; Pöschl, J; Ruef, P

    2015-01-01

    Determination of shear stresses at given shear rates with the LS 300 allows approximation of flow curves by mathematical models and to calculate viscosities of non-Newtonian fluids across the entire physiological shear range. Particular in preterm neonates, which in comparison to term neonates and adults have a substantially lower mean arterial blood pressure (MAP), rheological blood properties play a decisive role to maintain the perfusion. Whole blood viscosity was measured in umbilical cord blood taken from 34 preterm neonates using the LS 300 viscometer. In addition aggregation index, plasma viscosity, hematocrit and red blood cell (RBC) deformability was determined. The highest quality of approximation of the flow curve of whole blood was achieved by the method of Ostwald. Shear stresses of whole blood of preterm neonates were significantly lower compared to term neonates at similar shear rates (velocity range 6.16 s-1-50 s-1). With hematocrit calculated to 0.40 the related exponent (n) of the viscosity of preterm neonates (by Ostwald) showed a significant lower exponent (n) (0.71 ± 0.07) than term neonates (0.76 ± 0.06). The highest quality of approximation of the flow curve of plasma was achieved with the model of Ostwald in preterm neonates as well as in term neonates. The viscosity of plasma determined by Newton was lower for preterm neonates (0.89 ± 0.19) than for term neonates (1.04 ± 0.16). Concurrent to term neonates the whole blood of preterm neonates showed a very low aggregation index (term neonates 2.97 ± 2.10; preterm neonates 2.37 ± 1.32) and preterm neonates showed higher RBC deformability than term neonates. Because of the physiologically lower MAP and the particular viscous properties of neonatal blood special attention should be given when treating neonates with conventional blood products derived from adult donors. PMID:26444619

  11. Sound production in neonate sperm whales (L)

    NASA Astrophysics Data System (ADS)

    Madsen, P. T.; Carder, D. A.; Au, W. W. L.; Nachtigall, P. E.; Møhl, B.; Ridgway, S. H.

    2003-06-01

    Acoustic data from two sperm whale neonates (Physeter macrocephalus) in rehabilitation are presented and implications for sound production and function are discussed. The clicks of neonate sperm whale are very different from usual clicks of adult specimens in that neonate clicks are of low directionality [SL anomaly (0°-90°) <8 dB], long duration (2-12 ms), and low frequency (centroid frequency between 300 and 1700 Hz) with estimated SLs between 140 and 162 dB//1 μPa (rms). Such neonate clicks are unsuited for biosonar, but can potentially convey homing information between calves and submerged conspecifics in open ocean waters at ranges of some 2 km. Moreover, it is demonstrated that sperm whale clicks are produced at the anterior placed monkey lips, thereby substantiating a key point in the modified Norris and Harvey theory and supporting the unifying theory of sound production in odontocetes.

  12. Cerebral Sinovenous Thrombosis in Neonates and Children.

    PubMed

    Chung, Melissa G

    2016-03-01

    Investigators from Erasmus University Hospital in Belgium and Gustave-Dron Hospital and Roger-Salengro Hospital in France studied the clinical and neuroradiologic characteristics of cerebral sinovenous thrombosis (CSVT) in neonates and children. PMID:27396366

  13. The many etiologies of neonatal hypocalcemic seizures.

    PubMed

    Levy-Shraga, Yael; Dallalzadeh, Keren; Stern, Keren; Paret, Gideon; Pinhas-Hamiel, Orit

    2015-03-01

    Seizures during the neonatal period have a broad differential diagnosis. Unlike in developing countries where hypovitaminosis D and hypocalcemia constitutes a major cause of infantile seizures, the number of neonatal seizures attributed to hypocalcemia in developed countries has decreased dramatically due to the improvement of infant formulas and vitamin D supplementation. In these countries, most infants that present with hypocalcemic seizures have underlying endocrinological etiologies rather than dietary insufficiencies. Here, we describe 3 cases of neonatal seizures due to hypocalcemia. Although the symptoms and calcium concentrations at presentation were similar in all 3 cases, the course of the disease and the final diagnosis for each were distinct. The cases are presented along with a brief review of the pathophysiology, differential diagnosis, and treatment of neonatal hypocalcemia. PMID:25738238

  14. Neonatal euthanasia: moral considerations and criminal liability.

    PubMed

    Sklansky, M

    2001-02-01

    Despite tremendous advances in medical care for critically ill newborn infants, caregivers in neonatal intensive care units still struggle with how to approach those patients whose prognoses appear to be the most grim, and whose treatments appear to be the most futile. Although the practice of passive neonatal euthanasia, from a moral perspective, has been widely (albeit quietly) condoned, those clinicians and families involved in such cases may still be found legally guilty of child abuse or even manslaughter. Passive neonatal euthanasia remains both a moral dilemma and a legal ambiguity. Even the definition of passive euthanasia remains unclear. This manuscript reviews the basic moral and legal considerations raised by the current practice of neonatal euthanasia, and examines the formal position statements of the American Medical Association and the American Academy of Pediatrics. The paper concludes by emphasising the need, at least in the United States, to clarify the legal status of this relatively common medical practice. PMID:11233379

  15. Effect of vitamin K on neonatal erythrocytes.

    PubMed

    Shahal, Y; Zmora, E; Katz, M; Mazor, D; Meyerstein, N

    1992-01-01

    This study investigated the possible oxidative effect of vitamin K3 (menadione) and Vitamin K1 (Konakion) on neonatal erythrocytes by controlled in vitro exposure. Menadione caused only mild morphological changes and did not decrease ATP levels. However, it oxidized intracellular hemoglobin to methemoglobin in neonatal cells more than in adult cells. Reduced glutathione contents were higher in neonatal cells, but less available for antioxidant protection. Konakion did not increase methemoglobin levels in newborn infants after a prophylactic injection. In vitro exposure to Konakion did not affect reduced glutathione and ATP levels, nor did it oxidize hemoglobin. However, extensive morphological changes were observed, attributed to the effect of its solvent. Therefore, it seems that menadione, which is no longer administered to newborns, causes oxidative stress in neonatal cells whereas Konakion, the current vitamin K1, does not, either in in vitro studies or by therapeutic administration. PMID:1472579

  16. Reference ranges and cutoff levels of pneumococcal antibody global serum assays (IgG and IgG2) and specific antibodies in healthy children and adults.

    PubMed

    Rose, M A; Buess, J; Ventur, Y; Zielen, S; Herrmann, E; Schulze, J; Schubert, R

    2013-08-01

    Pneumococcal antibodies represent the acquisition of natural immunity. Determination of pneumococcal antibodies is an important screening tool for immunodeficiencies. Our study generated reference ranges and cutoff levels for pneumococcal antibody global serum assays correlated to a specific pneumococcal antibody ELISA. Specific pneumococcal antibody levels were measured from 457 children undergoing elective surgery and 46 healthy adult volunteers (88 with previous pneumococcal immunization from both groups), 22 severe immunodeficient subjects with ataxia telangiectasia (A-T, negative controls), and age-matched 36 healthy allergic asthmatics. We determined a representative panel of serotype-specific pneumococcal antibodies (serotype 4, 5, 6B, 7F, 14, 18C, 19F, 23F) by ELISA and global pneumococcal IgG and IgG2 antibodies by EIA. In vaccine-naïve healthy subjects, initial pneumococcal IgG geometric mean concentrations of 13.1 μg/ml were low in the first year of life and increased over the time, reaching adult levels (70.5 μg/ml) at age 8-12 years. In parallel, IgG2 antibodies increased from 20.7 % (0.5-1 year old) to adult proportions (>30 %) in preschoolers. Correlation between the pneumococcal IgG screening assay and specific pneumococcal antibody levels was acceptable (Pearson's coefficient r = 0.4455; p = 0.001). Cutoff levels showed high sensitivity, whereas specificity was high to moderate calculated from correlations with the specific ELISA. We provide reference ranges and cutoff levels for the interpretation of specific antibody determinations in the clinical setting. The global pneumococcal IgG/IgG2 assay is a suitable screening tool and correlates with the ELISA serotype-specific pneumococcal antibodies. However, results below our cutoff values should be re-evaluated by serotype-specific ELISA testing. PMID:23529214

  17. APPRAISAL OF PRENATAL ANTI-TOXOPLASMA GONDII (IGG+IGM)- IHA/IGM-ELISA SCREENING IN SINGLE SAMPLES VIA IGG AVIDITY TEST.

    PubMed

    El-Bali, Mohammed; Zaglool, Dina A M; Khodari, Yousif A W; Al-Harthi, Saeed A

    2016-04-01

    Congenital toxoplasmosis is associated with important morbidity and mortality. Since vertical transmission of Toxoplasma gondii can occur in acute cases, antenatal screening for recent infections is vital. Accurate determination of acute toxoplasmosis requires a combination of immunoassays, usually not routinely applied for screening purposes. This study evaluated the anti-T. gondii (IgG+IgM)/IgM prenatal screening procedure by IgG avidity assay. The routine prenatal screening for (IgG+IgM) anti-T. gondii by indirect hemagglutination (IHA) in serum samples was done of 2247 pregnant women who attended two hospitals between 2011 and 2013 revealed 487 (21.7%) positive samples. Examination of IHA-positive sera by IgM and IgG/IgG-avidity concurrent ELISA tests revealed 7 positive and 3 border-line IgM-ELISA titers during the initial check-up of 10 women, who were then followed up at 3-4 week-intervals. Among these, 4 (40%) showed simultaneous high avidity IgG antibodies, indicating distant infection by the parasite, and no anti-T. gondii specific IgG could be detected in follow-up sera of two cases (20%), indicating false IgM initial positive results. Only 4 (40%) women showed simultaneous IgM and low avidity IgG antibodies indicating active infections. Avoidance of an over-diagnosis of acute toxoplasmosis Anti-T. gondii (IgG+IgM)/IgM prenatal screening must be supplemented by a discriminative test like IgG avidity ELISA. PMID:27363056

  18. The role of IgG4 (+) plasma cells in the association of Hashimoto's thyroiditis with papillary carcinoma.

    PubMed

    Taşli, Funda; Ozkök, Güliz; Argon, Asuman; Ersöz, Didem; Yağci, Ayşe; Uslu, Adam; Erkan, Nazif; Salman, Tarik; Vardar, Enver

    2014-12-01

    Hashimoto's thyroiditis (HT) is considered to be a risk factor for the formation of papillary carcinoma. The association of IgG4-related sclerosing disease with tumor is reported to be as sporadic cases in many organs. In this study, it was intended to re-classify the HT diagnosed cases on the basis of the existence of IgG4 (+) plasma cells; to investigate the clinicopathologic and histopathologic features of the both groups; and in addition, to evaluate the papillary carcinoma prevalence in IgG4 (+) and IgG4 (-) HT cases as well as the prognostic parameters between these groups. Totally 59 cases between the years 2008-2013, 29 of which contain Hashimoto thyroiditis diagnosis in total thyroidectomy materials, and 30 of which contain the diagnosis of HT+papillary carcinoma, were included in the study. The materials were immunohistochemically applied IgG and IgG4; and the cases were classified in two groups as IgG4-positive HT and IgG4-negative HT containing cases, on the basis of IgG4/IgG rate. All histopathologic and clinicopathologic parameters between these two groups, as well as their association with papillary carcinoma were investigated. Thirty eight (64.4%) of total 59 cases were NonIgG4 thyroiditis, and 21 (35.5%) were IgG4 thyroiditis. Tumors were detected in 14 (36.8%) of the NonIgG4 thyroiditis cases, and in 16 (76.1%) of the IgG4 thyroiditis cases. The association of IgG4 thyroiditis with tumor is statistically significant (p < 0.004). Multifocality was found to be at a higher rate in IgG4 thyroiditis cases. Perithyroidal extension was detected in six of the cases with tumor, and five of the six cases were IgG4 thyroiditis cases. The association of IgG4 (+) HT cases with increased papillary carcinoma prevalence is suggestive of that IgG4 (+) plasma cells can play a role in carcinogenesis in papillary carcinomas developed in HTs, without a chronic sclerosing ground. In addition, although the number of cases is limited, the high-association of IgG4

  19. [High-frequency oscillatory ventilation in neonates].

    PubMed

    2002-09-01

    High-frequency oscillatory ventilation (HFOV) may be considered as an alternative in the management of severe neonatal respiratory failure requiring mechanical ventilation. In patients with diffuse pulmonary disease, HFOV can applied as a rescue therapy with a high lung volume strategy to obtain adequate alveolar recruitment. We review the mechanisms of gas exchange, as well as the indications, monitoring and special features of the use HVOF in the neonatal period. PMID:12199947

  20. Periventricular leukomalacia in a neonatal calf.

    PubMed

    Koyama, Kenji; Fujita, Riku; Maezawa, Masaki; Fukumoto, Natsuko; Horiuchi, Noriyuki; Inokuma, Hisashi; Kobayashi, Yoshiyasu

    2016-08-01

    A 10-day-old, Japanese Black, female calf had shown astasia since just after birth. Focal symmetrical periventricular malacic lesions of the cerebrum and suppurative arthritis of the left hip joint were observed in macroscopic examination. Histologically, the cerebral lesions were confirmed as periventricular leukomalacia (PVL). The location and histological features of the lesions were similar to PVL in humans, caused by neonatal ischemia/hypovolemia. This is the first report of PVL in a neonatal calf. PMID:27010465

  1. Maternal and neonatal outcomes of macrosomic pregnancies

    PubMed Central

    Weissmann-Brenner, Alina; Simchen, Michal J.; Zilberberg, Eran; Kalter, Anat; Weisz, Boaz; Achiron, Reuven; Dulitzky, Mordechai

    2012-01-01

    Summary Background To compare maternal and neonatal outcomes of term macrosomic and adequate for gestational age (AGA) pregnancies. Material/Methods A retrospective analysis was performed on all term singleton macrosomic (birth weight ≥4000 g) and AGA (birth weight >10th percentile and <4000 g) pregnancies delivered at our hospital between 2004 and 2008. Data collected included maternal age, gestational age at delivery, mode of delivery, birth weight, fetal gender, maternal and neonatal complications. Comparisons were made between macrosomic and AGA pregnancies and between different severities of macrosomia (4000–4250 g, 4250–4500 g and ≥4500 g). Results The study population comprised of 34,685 pregnancies. 2077 neonates had birth weight ≥4000 g. Maternal age and gestational age at delivery were significantly higher for macrosomic neonates. Significantly more macrosomic neonates were born by cesarean section, and were complicated with shoulder dystocia, neonatal hypoglycemia, and had longer hospitalization period (both in vaginal and cesarean deliveries). Specifically, the odds ratio (OR) relative to AGA pregnancies for each macrosomic category (4000–4250 g, 4250–4500 g and ≥4500 g) of shoulder dystocia was 2.37, 2.24, 7.61, respectively, and for neonatal hypoglycemia 4.24, 4.41, 4.15, respectively. The risk of post partum hemorrhage was statistically increased when birth weight was >4500 g (OR=5.23) but not for birth weight between 4000–4500 g. No differences were found in the rates of extensive perineal lacerations between AGA and the different macrosomic groups. Conclusions Macrosomia is associated with increased rate of cesarean section, shoulder dystocia, neonatal hypoglycemia, and longer hospitalization, but not associated with excessive perineal tears. Increased risk of PPH was found in the >4500g group. PMID:22936200

  2. Legal and ethical issues in neonatal nursing.

    PubMed

    2016-09-12

    Neonatal nurses regularly face complex legal and ethical dilemmas. This article discusses the hypothetical case of Jack, a two-day-old infant, born at 39 weeks' gestation, and diagnosed with trisomy 13 (syndrome), a life-limiting condition and being cared for in a neonatal intensive care unit. Jack's prognosis is poor and he is not expected to live past two weeks of age. PMID:27615591

  3. Fading kitten syndrome and neonatal isoerythrolysis.

    PubMed

    Bücheler, J

    1999-07-01

    Fading kitten syndrome includes noninfectious and infectious causes for neonatal death (birth to weaning age). Noninfectious causes are mostly responsible for mortality in the first week of life and include congenital disorders, low birth weights, trauma, malnutrition, environmental causes, and neonatal isoerythroylsis. Infectious causes are more prevalent at 3-4 weeks of age. This article discusses the causes, clinical signs, and management of fading kitten syndrome. PMID:10390788

  4. Neonatal osteomyelitis examined by bone scintigraphy

    SciTech Connect

    Bressler, E.L.; Conway, J.J.; Weiss, S.C.

    1984-09-01

    Thirty-three infants less than six weeks of age and suspected of having osteomyelitis were examined by bone scintigraphy. Each of the 25 sites of proved osteomyelitis in 15 individuals demonstrated abnormal radionuclide localization. Ten additional scintigraphically positive but radiographically normal sites were detected. Optimal quality scintigrams of the growth plate complex and osteomyelitis in neonates appeared similar to those in older children. All neonates suspected of having osteomyelitis should be studied with bone scintigraphy following initial radiographs.

  5. Conjugation Inhibitors and Early Neonatal Hyperbilirubinaemia

    PubMed Central

    Cole, A. P.; Hargreaves, T.

    1972-01-01

    Milk and serum were obtained from 50 mothers on the 6th day post partum and examined for inhibitory activity against bilirubin conjugation in rat liver slices. Neonatal serum bilirubin levels were also analysed at this time. There was no relation between the amount of inhibitory substance in breast milk or serum and the degree of neonatal hyperbilirubinaemia. It was observed that inhibitory activity increased in frozen breast milk but not in frozen autoclaved breast milk. PMID:5034671

  6. Periventricular leukomalacia in a neonatal calf

    PubMed Central

    KOYAMA, Kenji; FUJITA, Riku; MAEZAWA, Masaki; FUKUMOTO, Natsuko; HORIUCHI, Noriyuki; INOKUMA, Hisashi; KOBAYASHI, Yoshiyasu

    2016-01-01

    A 10-day-old, Japanese Black, female calf had shown astasia since just after birth. Focal symmetrical periventricular malacic lesions of the cerebrum and suppurative arthritis of the left hip joint were observed in macroscopic examination. Histologically, the cerebral lesions were confirmed as periventricular leukomalacia (PVL). The location and histological features of the lesions were similar to PVL in humans, caused by neonatal ischemia/hypovolemia. This is the first report of PVL in a neonatal calf. PMID:27010465

  7. Milk allergy in the neonatal intensive care unit: comparison between premature and full-term neonates

    PubMed Central

    Iwakura, Hideo; Ohtsuka, Harumi; Kohno, Yoichi; Shimojo, Naoki

    2013-01-01

    Background There have been several reports on neonates with milk allergy in a neonatal ward. This type of allergy is mostly categorized as a non-IgE-mediated food allergy. Although most cases of milk allergy occur in the first few months of life, the differences in clinical characteristics between premature and full-term neonates are still unclear. Objective This study aimed to clarify the differences in clinical characteristics of milk allergy between premature and full-term neonates. Methods We retrospectively evaluated 2,116 neonates admitted to the Department of Neonatology, Chiba Kaihin Municipal Hospital, between 2001 and 2007. Results We identified 24 neonates strongly suspected of having milk allergy because of symptoms, such as bloody stools, repeated vomiting, diminished sucking and abdominal distension, as well as objective laboratory findings of eosinophilia in stool cytology and/or positive results for a rectal milk challenge test. Twelve of these 24 neonates were premature (median gestational age, 31 ± 3 weeks; median birth weight, 1,656 ± 592 g) and the other 12 were full-term (median gestational age, 38 ± 1 weeks; median birth weight, 2,760 ± 560 g). There were no differences in symptoms and time to start of feeding between premature and full-term neonates, but there was a significant difference in the median postnatal age at onset (premature neonates: 23 days; vs. full-term neonates: 3.5 days; p < 0.01). Conclusion All premature neonates developed a milk allergy after 32 weeks of corrected gestational age, suggesting that the development of milk allergy requires a certain degree of immunological maturation. PMID:23403887

  8. Nutrition support after neonatal cardiac surgery.

    PubMed

    Owens, Joyce L; Musa, Ndidiamaka

    2009-01-01

    Congenital heart disease is the most common birth defect in the United States, with an estimated frequency of approximately 12-14 of 1000 live births per year. Neonates with congenital heart disease often need palliative or corrective surgery requiring cardiopulmonary bypass during the first weeks of life. The neonate undergoing cardiopulmonary bypass surgery experiences a more profound metabolic response to stress than that seen in older children and adults undergoing surgery. However, compared with older children and adults, the neonate has less metabolic reserves and is extremely vulnerable to the negative metabolic impact induced by stress, which can lead to suboptimal wound healing and growth failure. There are complications associated with the metabolic derangements of neonatal surgery requiring cardiopulmonary bypass, including but not limited to acute renal failure, chylothorax, and neurological dysfunction. This article discusses the importance of nutrition and metabolic support for the neonate undergoing cardiopulmonary bypass and the immediate postoperative nutrition needs of such a patient. Also, this article uses a case study to examine the feeding methodology used at one particular institution after neonatal cardiac surgery. The purpose of the case study is to provide an illustration of the many factors and obstacles that clinicians often face in the provision and timing of nutrition support. PMID:19321898

  9. Selenium status in neonates with connatal infection.

    PubMed

    Wiehe, Lennart; Cremer, Malte; Wisniewska, Monika; Becker, Niels-Peter; Rijntjes, Eddy; Martitz, Janine; Hybsier, Sandra; Renko, Kostja; Bührer, Christoph; Schomburg, Lutz

    2016-08-01

    Infectious diseases impair Se metabolism, and low Se status is associated with mortality risk in adults with critical disease. The Se status of neonates is poorly characterised, and a potential impact of connatal infection is unknown. We hypothesised that an infection negatively affects the Se status of neonates. We conducted an observational case-control study at three intensive care units at the Charité-Universitätsmedizin Berlin, Germany. Plasma samples were collected from forty-four neonates. On the basis of clinical signs for bacterial infection and concentrations of IL-6 or C-reactive protein, neonates were classified into control (n 23) and infected (n 21) groups. Plasma Se and selenoprotein P (SePP) concentrations were determined by X-ray fluorescence and ELISA, respectively, at day of birth (day 1) and 48 h later (day 3). Se and SePP showed a positive correlation in both groups of neonates. Se concentrations indicative of Se deficit in adults (500 ng/l). During antibiotic therapy, SePP increased significantly from day 1 (1·03 (sd 0·10) mg/l) to day 3 (1·34 (sd 0·10) mg/l), indicative of improved hepatic Se metabolism. We conclude that both Se and SePP are suitable biomarkers for assessing Se status in neonates and for identifying subjects at risk of deficiency. PMID:27267586

  10. Antiepileptic drug treatment strategies in neonatal epilepsy.

    PubMed

    Hernan, A E; Holmes, G L

    2016-01-01

    The highest risk of seizures across the lifespan is in the neonatal period. The enhanced excitability of the immature brain compared to the mature brain is related to the sequential development and expression of essential neurotransmitter signaling pathways. During the neonatal period there is an overabundance of excitatory receptors, and γ-amino-butyric acid (GABA) is potentially depolarizing, as opposed to hyperpolarizing in the older brain. While this enhanced excitability is required for regulation of activity-dependent synapse formation and refining of synaptic connections that are necessary for normal brain development, enhanced excitability predisposes the immature brain to seizures. In addition to being common, neonatal seizures are very difficult to treat; antiepileptic drugs used in older children and adults are less efficacious, and possibly detrimental to brain development. In an effort to target the unique features of neurotransmission in the neonate, bumetanide, an NKCC1 inhibitor which reduces intraneuronal Cl(-) and induces a significant shift of EGABA toward more hyperpolarized values in vitro, has been used to treat neonatal seizures. As the understanding of the pathophysiology of genetic forms of neonatal epilepsy has evolved there have been a few successful attempts to pharmacologically target the mutated protein. This approach, while promising, is challenging due to the findings that the genetic syndromes presenting in infancy demonstrate genetic heterogeneity in regard to both the mutated gene and its function. PMID:27323943

  11. Conformational difference in human IgG2 disulfide isoforms revealed by hydrogen/deuterium exchange mass spectrometry.

    PubMed

    Zhang, Aming; Fang, Jing; Chou, Robert Y-T; Bondarenko, Pavel V; Zhang, Zhongqi

    2015-03-17

    Both recombinant and natural human IgG2 antibodies have several different disulfide bond isoforms, which possess different global structures, thermal stabilities, and biological activities. A detailed mapping of the structural difference among IgG2 disulfide isoforms, however, has not been established. In this work, we employed hydrogen/deuterium exchange mass spectrometry to study the conformation of three major IgG2 disulfide isoforms known as IgG2-B, IgG2-A1, and IgG2-A2 in two recombinant human IgG2 monoclonal antibodies. By comparing the protection factors between amino acid residues in isoforms B and A1 (the classical form), we successfully identified several local regions in which the IgG2-B isoform showed more solvent protection than the IgG2-A1 isoform. On the basis of three-dimensional structural models of IgG2, these identified regions were located on the Fab domains, close to the hinge, centered on the side where the two Fab arms faced each other in spatial proximity. We speculated that in the more solvent-protected B isoform, the two Fab arms were brought into contact by the nonclassical disulfide bonds, resulting in a more compact global structure. Loss of Fab domain flexibility in IgG2-B could limit its ability to access cell-surface epitopes, leading to reduced antigen binding potency. The A2 isoform was previously found to have disulfide linkages similar to those of the classical A1 isoform, but with different biophysical behaviors. Our data indicated that, compared to IgG2-A1, IgG2-A2 had less solvent protection in some heavy-chain Fab regions close the hinge, suggesting that the A2 isoform had more flexible Fab domains. PMID:25730439

  12. Human placenta: relative content of antibodies of different classes and subclasses (IgG1-IgG4) containing lambda- and kappa-light chains and chimeric lambda-kappa-immunoglobulins.

    PubMed

    Lekchnov, Evgenii A; Sedykh, Sergey E; Dmitrenok, Pavel S; Buneva, Valentina N; Nevinsky, Georgy A

    2015-06-01

    The specific organ placenta is much more than a filter: it is an organ that protects, feeds and regulates the growth of the embryo. Affinity chromatography, ELISA, SDS-PAGE and matrix-assisted laser desorption ionization mass spectrometry were used. Using 10 intact human placentas deprived of blood, a quantitative analysis of average relative content [% of total immunoglobulins (Igs)] was carried out for the first time: (92.7), IgA (2.4), IgM (2.5), kappa-antibodies (51.4), lambda-antibodies (48.6), IgG1 (47.0), IgG2 (39.5), IgG3 (8.8) and IgG4 (4.3). It was shown for the first time that placenta contains sIgA (2.5%). In the classic paradigm, Igs represent products of clonal B-cell populations, each producing antibodies recognizing a single antigen. There is a common belief that IgGs in mammalian biological fluids are monovalent molecules having stable structures and two identical antigen-binding sites. However, similarly to human milk Igs, placenta antibodies undergo extensive half-molecule exchange and the IgG pool consists of 43.5 ± 15.0% kappa-kappa-IgGs and 41.6 ± 17.0% lambda-lambda-IgGs, while 15.0 ± 4.0% of the IgGs contained both kappa- and lambda-light chains. Kappa-kappa-IgGs and lambda-lambda-IgGs contained, respectively (%): IgG1 (47.7 and 34.4), IgG2 (36.3 and 44.5), IgG3 (7.4 and 11.8) and IgG4 (7.5 and 9.1), while chimeric kappa-lambda-IgGs consisted of (%): 43.5 IgG1, 41.0 IgG2, 5.6 IgG3 and 7.9 IgG4. Our data are indicative of the possibility of half-molecule exchange between placenta IgGs of various subclasses, raised against different antigens, which explains a very well-known polyspecificity and cross-reactivity of different human IgGs. PMID:25644595

  13. Incidence of CMV co-infection in HIV-positive women and their neonates in a tertiary referral centre: a cohort study.

    PubMed

    Reitter, A; Buxmann, H; Haberl, A E; Schlösser, R; Kreibich, M; Keppler, O T; Berger, A

    2016-02-01

    Co-infection with CMV in HIV-positive pregnant women is associated with perinatal mother-to-child transmission (MTCT) of both viruses. This retrospective study reports on the incidence of maternal and neonatal CMV (presence of anti-CMV IgG and IgM, CMV DNA PCR and/or CMV virus isolation) in high-risk pregnancies due to maternal HIV infection, MTCT of HIV and/or CMV. One hundred and eleven maternal samples and 75 matched neonatal samples were available for HIV and subsequent CMV testing. In this cohort of HIV-positive pregnant women, 96 (86.5 %) serum samples were anti-CMV IgG positive. In nine (9.4 %) of these, anti-CMV IgM was detected, and in none of them a maternal primary CMV infection was suspected. Fifty-seven (51.8 %) maternal serum samples were tested retrospectively by CMV DNA PCR; one sample was positive (0.9 %). All matched neonates were tested for HIV by PCR in the first month of life; HIV transmission was detected in one case. In 74 (67.2 %) of neonates, CMV testing was performed. Sixty-six of these serum samples were tested retrospectively by CMV DNA PCR. Two newborns (2.7 %) showed laboratory markers for CMV infection (one by detection of CMV DNA in plasma, and one by isolation of CMV from a urine sample). In the follow-up, neither of these two showed clinical signs for active CMV disease. We discussed these findings in the light of the national official guidelines. All CMV transmissions occurred due to maternal reinfection or endogenous reactivation. This suggests the success of highly active antiretroviral therapy in preventing MTCT of HIV and CMV disease and highlights the importance of adequate care and follow-up. PMID:26155982

  14. Role of Cytomegalovirus (CMV) IgG Avidity Testing in Diagnosing Primary CMV Infection during Pregnancy

    PubMed Central

    Lapé-Nixon, Mary

    2014-01-01

    The risk of intrauterine transmission of cytomegalovirus (CMV) during pregnancy is much greater for women who contract primary CMV infection after conception than for women with evidence of infection (circulating CMV antibodies) before conception. Thus, laboratory tests that aid in the identification of recent primary CMV infection are important tools for managing the care of pregnant women suspected of having been exposed to CMV. CMV IgM detection is a sensitive marker of primary CMV infection, but its specificity is poor because CMV IgM is also produced during viral reactivation and persists following primary infection in some individuals. Studies conducted over the last 20 years convincingly demonstrate that measurement of CMV IgG avidity is both a sensitive and a specific method for identifying pregnant women with recent primary CMV infection and thus at increased risk for vertical CMV transmission. IgG avidity is defined as the strength with which IgG binds to antigenic epitopes expressed by a given protein; it matures gradually during the 6 months following primary infection. Low CMV IgG avidity is an accurate indicator of primary infection within the preceding 3 to 4 months, whereas high avidity excludes primary infection within the preceding 3 months. In this minireview, we summarize published data demonstrating the clinical utility of CMV IgG avidity results for estimating time since primary infection in pregnant women, describe commercially available CMV IgG avidity assays, and discuss some of the issues and controversies surrounding CMV IgG avidity testing during pregnancy. PMID:25165026

  15. Comparison of Four Commercially Available Avidity Tests for Toxoplasma gondii-Specific IgG Antibodies

    PubMed Central

    Breit, L.; Cimon, B.; Franck, J.; Fricker-Hidalgo, H.; Godineau, N.; Houze, S.; Paris, L.; Pelloux, H.; Villena, I.

    2013-01-01

    Toxoplasma infection in pregnant women may cause congenital toxoplasmosis. Diagnosis of infection is based on serological tests aimed at detecting IgM and IgG antibodies against Toxoplasma gondii. However, IgM antibodies are not an accurate marker for discriminating between acute and latent infection. Detection of residual or persistent IgM may occur months or even years after primary infection, while the IgG avidity test is a rapid means of identifying latent infections in pregnant women who exhibit both IgG and IgM anti-Toxoplasma antibodies on initial testing during pregnancy. In this study, we assessed and compared the performances of four commercially available Toxoplasma IgG avidity tests in immunocompetent and immunocompromised patients with acute and latent toxoplasmosis. The positive predictive value of high avidity to confirm latent toxoplasmosis was 100% for all the assays, indicating that high avidity is a hallmark of latent infection. However, the negative predictive value of high avidity ranged from 99.2% (bioMérieux) to 95.3% (Abbott), indicating that acute toxoplasmosis could not be reliably diagnosed based on low IgG avidity alone. Thus, the avidity test provides a rapid means for identifying latent Toxoplasma infection in immunocompetent pregnant women presenting both IgG and IgM anti-Toxoplasma antibodies on initial testing. In terms of cost-effectiveness, avidity testing is a powerful tool that optimizes screening and follow-up of pregnant women while minimizing the costs of screening by avoiding subsequent costly maternal and fetal investigation and unnecessary treatment. The cheapest assay, Vidas Toxo IgG Avidity, also had the best performance for the diagnosis of latent toxoplasmosis. PMID:23239801

  16. Comparison of four commercially available avidity tests for Toxoplasma gondii-specific IgG antibodies.

    PubMed

    Villard, O; Breit, L; Cimon, B; Franck, J; Fricker-Hidalgo, H; Godineau, N; Houze, S; Paris, L; Pelloux, H; Villena, I; Candolfi, E

    2013-02-01

    Toxoplasma infection in pregnant women may cause congenital toxoplasmosis. Diagnosis of infection is based on serological tests aimed at detecting IgM and IgG antibodies against Toxoplasma gondii. However, IgM antibodies are not an accurate marker for discriminating between acute and latent infection. Detection of residual or persistent IgM may occur months or even years after primary infection, while the IgG avidity test is a rapid means of identifying latent infections in pregnant women who exhibit both IgG and IgM anti-Toxoplasma antibodies on initial testing during pregnancy. In this study, we assessed and compared the performances of four commercially available Toxoplasma IgG avidity tests in immunocompetent and immunocompromised patients with acute and latent toxoplasmosis. The positive predictive value of high avidity to confirm latent toxoplasmosis was 100% for all the assays, indicating that high avidity is a hallmark of latent infection. However, the negative predictive value of high avidity ranged from 99.2% (bioMérieux) to 95.3% (Abbott), indicating that acute toxoplasmosis could not be reliably diagnosed based on low IgG avidity alone. Thus, the avidity test provides a rapid means for identifying latent Toxoplasma infection in immunocompetent pregnant women presenting both IgG and IgM anti-Toxoplasma antibodies on initial testing. In terms of cost-effectiveness, avidity testing is a powerful tool that optimizes screening and follow-up of pregnant women while minimizing the costs of screening by avoiding subsequent costly maternal and fetal investigation and unnecessary treatment. The cheapest assay, Vidas Toxo IgG Avidity, also had the best performance for the diagnosis of latent toxoplasmosis. PMID:23239801

  17. IgG4-related disease: current challenges and future prospects

    PubMed Central

    Lang, David; Zwerina, Jochen; Pieringer, Herwig

    2016-01-01

    Immunoglobulin G4-related disease (IgG4-RD) represents an immune-mediated fibroinflammatory condition with a characteristic histopathological appearance that can affect various organs. Although numerous single-organ manifestations have been described more than a century ago, its systemic nature and unique features were only discovered in the last 2 decades, when IgG4-RD emerged as a new entity of disease. IgG4-RD is usually considered a rare disease, but its true epidemiology has not yet been fully clarified. Also, despite recent advances in the identification of the underlying immunological processes, its pathophysiology is only incompletely understood till now. The diagnostic workup of IgG4-RD is complex and usually requires a combination of clinical examination, imaging, histological, and serological analyses. However, no finding alone is specific for IgG4-RD. Therefore, its diagnosis requires careful interpretation of examination results in context with the patient’s clinical appearance as well as the exclusion of a broad variety of differential diagnoses. The past years brought rapid advances concerning this novel disease entity: diagnostic criteria, further insights into the underlying immunological processes, new biomarkers, and novel therapeutic approaches were proposed and widened the knowledge in the field of IgG4-RD. Still, a greater number of questions remain unanswered, and many recent developments require further discussion and proof from clinical trials. This review should give an overview on current knowledge and future perspectives in epidemiology, pathophysiology, diagnosis, and therapy of IgG4-RD. PMID:26929632

  18. Conformational plasticity of IgG during protein A affinity chromatography.

    PubMed

    Gagnon, Pete; Nian, Rui

    2016-02-12

    Single step elution of a protein A column with 100mM acetate pH 3.5 produced a curvilinear gradient with pH dropping steeply at first then more gradually as it approached endpoint. IgG with a native hydrodynamic diameter of 11.5 nm began to elute at pH 6.0 with a size of 9.4 nm. IgG size continued to decrease across the peak, reaching a minimum of 2.2 nm at pH 3.9. Secondary structure of early eluting IgG was only mildly affected but later eluting fractions became increasingly non-native with the 2.2 nm population exhibiting the highest proportion of β-sheet and lowest random coil of all conformations. Size reduction and structural change of IgG through this portion of the elution peak were attributed dominantly to a pre-existing tendency of highly concentrated IgG to adopt reduced size conformations at low pH and conductivity, facilitated by the known conformational relaxation of IgG by its interaction with protein A. IgG size increased to 10.4 nm as elution pH approached 3.5 across the tailing fractions. Major loss of β-sheet and increase of α-helix and random coil were observed in parallel. Late elution of this population was attributed to it being eluted from interactions with 2 distinct protein A domains, one bound to each side of the Fc region, creating a higher dissociation constant than single-site Fc-protein A interactions, and requiring more severely disruptive conditions for elution. The high degree of conformational disruption was attributed to simultaneous interaction of both heavy chains with protein A. PMID:26805601

  19. IgG4-related disease: A relatively new concept for clinicians.

    PubMed

    Vasaitis, Lilian

    2016-01-01

    IgG4-related disease (IgG4-RD) is a recently recognized chronic fibrotic inflammation, which can affect almost every organ, and may come to clinical attention first due to visible organ swelling or organ dysfunction, or is identified incidentally by imaging and specific biopsy. The disorder has an allergic background and is immune-mediated. Up-regulated responses of T helper 2 and T regulatory cells and their cytokines play a major role in disease progression. About 30-50% of patients are atopic or have mild eosinophilia. IgG4-RD predominantly affects middle-aged male patients. The cornerstones of diagnosis of the disease are compatible clinical features and typical histopathology. Swelling of salivary and lacrimal glands, lymphadenopathy, and type 1 autoimmune pancreatitis (AIP) are the most common manifestations of the disease. However, other tissues and organs, such as retroperitoneum, lung, kidney, aorta, upper airways, thyroid gland, meninges, heart, mesenterium and skin may be involved. Typical histopathology is lymphoplasmacytic infiltration abundant in IgG4-positive plasma cells, storiform-type fibrosis, and obliterative phlebitis. Elevated serum IgG4 concentration supports the diagnosis. Characteristic imaging features such as a "capsule-like rim" surrounding the pancreatic lesions is highly specific to type 1 AIP. 18F-fluorodeoxyglucose positron emission tomography/computed tomography enables mapping the sites of inflammation, permits evaluation of the extent of the disease, helps in guiding biopsy decision, and may be used in monitoring response to treatment. Glucocorticoids alone or in combination with B-cell depletion with rituximab induces prompt clinical response to IgG4-RD. This article reviews the current understanding, different clinical manifestations, and approaches to diagnosis and treatment of IgG4-RD. PMID:26481243

  20. IgG4-Related Esophageal Disease Presenting as Esophagitis Dissecans Superficialis With Chronic Strictures.

    PubMed

    Dumas-Campagna, Myriam; Bouchard, Simon; Soucy, Genevieve; Bouin, Mickael

    2014-08-01

    IgG4-related disease is a recently recognized autoimmune systemic disorder that has been described in various organs. The disease is characterized histologically by a dense lymphoplasmocytic infiltrate of IgG4-positive cells, storiform fibrosis and can be associated with tumefactive lesions. IgG4-related disease involving the upper gastrointestinal tract is rare and only two previous case reports have reported IgG4-related esophageal disease. We report the case of a 63-year-old female patient with a long-standing history of severe dysphagia and odynophagia with an initial diagnosis of reflux esophagitis. Symptoms persisted despite anti-acid therapy and control esophagogastroduodenoscopy (EGD) revealed endoscopic images consistent with esophagitis dissecans superficialis (sloughing esophagitis). An underlying autoimmune process was suspected and immunosuppressant agents were tried to control her disease. The patient eventually developed disabling dysphagia secondary to multiple chronic esophageal strictures. A diagnosis of IgG4-related disease was eventually made after reviewing esophageal biopsies and performing an immunohistochemical study with an anti-IgG4 antibody. Treatment attempts with corticosteroids and rituximab was not associated with a significant improvement of the symptoms of dysphagia and odynophagia, possibly because of the chronic nature of the disease associated with a high fibrotic component. Our case report describes this unique case of IgG4-related esophageal disease presenting as chronic esophagitis dissecans with strictures. We also briefly review the main histopathological features and treatment options in IgG4-related disease. PMID:24883156

  1. Evaluating breast lymphoplasmacytic infiltrates: a multiparameter immunohistochemical study, including assessment of IgG4.

    PubMed

    Berg, Aaron N; Soma, Lorinda; Clark, Beth Z; Swerdlow, Steven H; Roth, Christine G

    2015-08-01

    Lymphoplasmacytic infiltrates in the breast, a modified skin appendage, include lymphocytic lobulitis, other nonspecific benign proliferations, and mucosa-associated lymphoid tissue (MALT)-type lymphoma. Distinguishing these entities, all of which may be B-cell rich and may have associated sclerosis, can be difficult. In addition, the proportion that represents IgG4-related disease is unknown, and the similarity of MALT lymphomas to primary cutaneous marginal zone lymphoma is uncertain. To address these questions, the clinical, histologic, and immunohistochemical features of 50 benign and malignant breast lymphoplasmacytic infiltrates (10 lymphocytic lobulitis, 1 granulomatous, 19 not otherwise specified, 20 MALT lymphomas) were evaluated. Compared with the MALT lymphomas, benign cases had a less dense infiltrate (P < .001), fewer but more histologically apparent germinal centers (P < .001), and more marked fibrosis (P < .0001). Greater than 60% B cells were present in 23% (7/30) benign cases versus 75% (15/20) MALT lymphomas (P = .0003). Plasma cells were predominantly IgG+ in 83% (24/29) benign cases and predominantly IgM+ in 73% (14/19) MALT lymphomas (P < .0001). None of the benign cases had greater than 50 IgG4+ plasma cells/high-power field, and only 1 lymphocytic lobulitis case had an IgG4/IgG ratio exceeding 40% and no clinical evidence for extramammary IgG4-related disease. Although there may be some overlapping features, routine histopathology together with limited immunohistochemical stains can distinguish benign from neoplastic lymphoplasmacytic infiltrates in the breast. Despite frequent sclerosis, the breast is not a common site of unrecognized IgG4-related sclerosing disease. Although there are similarities, breast MALT lymphomas can be separated from cutaneous marginal zone lymphoma. PMID:26026200

  2. Virus-Specific Immunity in Neonatal and Adult Mouse Rotavirus Infection

    PubMed Central

    Sheridan, J. F.; Eydelloth, R. S.; Vonderfecht, S. L.; Aurelian, L.

    1983-01-01

    Mouse rotavirus (epizootic diarrhea of infant mice) was used as a model to study the role of virus-specific immunity in infection and diarrheal disease. The distribution of viral antigen in intestinal tissues was determined by immunofluorescent staining with anti-simian rotavirus (SA-11) serum. The location and proportion of antigen-positive cells appeared to vary as a function of time postinfection and age of the animal at the time of infection. In animals infected at 1 and 7 days of age, antigen-positive cells (5 to 25%) were first detected (1 day postinfection) in the proximal segment of the small intestine, and infection progressed to the middle and distal segments. At 10 days postinfection, virus-infected cells were no longer observed in the proximal segment. In animals infected at 21 days of age (disease-free), a significantly lower proportion of cells were antigen positive (2 to 5%), and they were restricted to the middle and distal segments of the small intestine. Infection, defined according to the presence of virus and viral antigens in intestinal tissues and by seroconversion in the immunoglobulin M (IgM) isotype as determined by enzyme-linked immunosorbent assay with SA-11 antigen, was observed for all age groups (neonatal to adult), even in the presence of virus-specific serum or intestinal immunoglobulins. On the other hand, diarrheal disease was not detected in neonatal mice (1 to 3 days old) positive for passively acquired virus-specific intestinal IgG. The presence of virus-specific IgA in the intestinal tract at the time of infection did not protect from subsequent diarrheal disease. Virus-specific, cell-mediated immunity, determined by a delayed-type hypersensitivity response, did not develop in neonatal mice infected at 5 and 12 days of age. Reinfection of adult mice was associated with suppression of virus-specific delayed-type hypersensitivity and a significant decrease in the titers of the virus-specific serum IgG and IgA. Images PMID:6299952

  3. Cause-specific neonatal mortality: analysis of 3772 neonatal deaths in Nepal, Bangladesh, Malawi and India

    PubMed Central

    Fottrell, Edward; Osrin, David; Alcock, Glyn; Azad, Kishwar; Bapat, Ujwala; Beard, James; Bondo, Austin; Colbourn, Tim; Das, Sushmita; King, Carina; Manandhar, Dharma; Manandhar, Sunil; Morrison, Joanna; Mwansambo, Charles; Nair, Nirmala; Nambiar, Bejoy; Neuman, Melissa; Phiri, Tambosi; Saville, Naomi; Sen, Aman; Seward, Nadine; Shah Moore, Neena; Shrestha, Bhim Prasad; Singini, Bright; Tumbahangphe, Kirti Man; Costello, Anthony; Prost, Audrey

    2015-01-01

    Objective Understanding the causes of death is key to tackling the burden of three million annual neonatal deaths. Resource-poor settings lack effective vital registration systems for births, deaths and causes of death. We set out to describe cause-specific neonatal mortality in rural areas of Malawi, Bangladesh, Nepal and rural and urban India using verbal autopsy (VA) data. Design We prospectively recorded births, neonatal deaths and stillbirths in seven population surveillance sites. VAs were carried out to ascertain cause of death. We applied descriptive epidemiological techniques and the InterVA method to characterise the burden, timing and causes of neonatal mortality at each site. Results Analysis included 3772 neonatal deaths and 3256 stillbirths. Between 63% and 82% of neonatal deaths occurred in the first week of life, and males were more likely to die than females. Prematurity, birth asphyxia and infections accounted for most neonatal deaths, but important subnational and regional differences were observed. More than one-third of deaths in urban India were attributed to asphyxia, making it the leading cause of death in this setting. Conclusions Population-based VA methods can fill information gaps on the burden and causes of neonatal mortality in resource-poor and data-poor settings. Local data should be used to inform and monitor the implementation of interventions to improve newborn health. High rates of home births demand a particular focus on community interventions to improve hygienic delivery and essential newborn care. PMID:25972443

  4. Clinicopathological analysis of salivary gland tissue from patients with IgG4-related disease.

    PubMed

    Takano, Kenichi; Nomura, Kazuaki; Abe, Ayumi; Kamekura, Ryuta; Yamamoto, Motohisa; Ichimiya, Shingo; Takahashi, Hiroki; Himi, Tetsuo

    2016-07-01

    Conclusion The diagnosis of immunoglobulin G4-related disease (IgG4-RD) should be based on the morphology of tissue biopsy, and this study recommends a submandibular gland (SMG) biopsy for accurate diagnosis and to exclude malignant disease. Objective To clarify which type of biopsy specimen (SMG or labial salivary gland [LSG]) should be taken from patients with IgG4-RD. Methods This study included 33 patients with IgG4-RD (21 women; 12 men) who were subjected to both SMG and LSG biopsies at Sapporo Medical University between 2011-2015. Tissues obtained from the SMG and LSG specimens were evaluated. Results All SMG specimens satisfied the diagnostic criteria for IgG4-RD, whereas 19 (57.6%) LSG specimens satisfied the diagnostic criteria for IgG4-RD. Histological evaluation showed fibrosis in all the SMG specimens and in eight LSG specimens (24.2%). Obliterative phlebitis was seen in nine SMG specimens (27.3%), but it was absent in all the LSG specimens. PMID:27007955

  5. Human IgG1 antibodies suppress angiogenesis in a target-independent manner

    PubMed Central

    Bogdanovich, Sasha; Kim, Younghee; Mizutani, Takeshi; Yasuma, Reo; Tudisco, Laura; Cicatiello, Valeria; Bastos-Carvalho, Ana; Kerur, Nagaraj; Hirano, Yoshio; Baffi, Judit Z; Tarallo, Valeria; Li, Shengjian; Yasuma, Tetsuhiro; Arpitha, Parthasarathy; Fowler, Benjamin J; Wright, Charles B; Apicella, Ivana; Greco, Adelaide; Brunetti, Arturo; Ruvo, Menotti; Sandomenico, Annamaria; Nozaki, Miho; Ijima, Ryo; Kaneko, Hiroki; Ogura, Yuichiro; Terasaki, Hiroko; Ambati, Balamurali K; Leusen, Jeanette HW; Langdon, Wallace Y; Clark, Michael R; Armour, Kathryn L; Bruhns, Pierre; Verbeek, J Sjef; Gelfand, Bradley D; De Falco, Sandro; Ambati, Jayakrishna

    2016-01-01

    Aberrant angiogenesis is implicated in diseases affecting nearly 10% of the world’s population. The most widely used anti-angiogenic drug is bevacizumab, a humanized IgG1 monoclonal antibody that targets human VEGFA. Although bevacizumab does not recognize mouse Vegfa, it inhibits angiogenesis in mice. Here we show bevacizumab suppressed angiogenesis in three mouse models not via Vegfa blockade but rather Fc-mediated signaling through FcγRI (CD64) and c-Cbl, impairing macrophage migration. Other approved humanized or human IgG1 antibodies without mouse targets (adalimumab, alemtuzumab, ofatumumab, omalizumab, palivizumab and tocilizumab), mouse IgG2a, and overexpression of human IgG1-Fc or mouse IgG2a-Fc, also inhibited angiogenesis in wild-type and FcγR humanized mice. This anti-angiogenic effect was abolished by Fcgr1 ablation or knockdown, Fc cleavage, IgG-Fc inhibition, disruption of Fc-FcγR interaction, or elimination of FcRγ-initated signaling. Furthermore, bevacizumab’s Fc region potentiated its anti-angiogenic activity in humanized VEGFA mice. Finally, mice deficient in FcγRI exhibited increased developmental and pathological angiogenesis. These findings reveal an unexpected anti-angiogenic function for FcγRI and a potentially concerning off-target effect of hIgG1 therapies. PMID:26918197

  6. IgG4-Related Lung Disease Associated with Usual Interstitial Pneumonia.

    PubMed

    Schneider, Frank; Veraldi, Kristen L; Levesque, Marc C; Colby, Thomas V; S Yi, Eunhee

    2016-01-01

    We report a case of immunoglobulin(Ig)G4-related disease with the radiologic and histopathological manifestations resembling usual interstitial pneumonia (UIP). The patient was a 62-year-old man who presented with progressive dyspnea of insidious onset. High resolution computed tomography of the chest showed lower-lobe predominant peripheral reticulation and traction bronchiectasis but no honeycomb change. Microscopic examination of the surgical lung biopsy showed characteristic features of UIP including architectural distortion by fibrosis with peripheral and paraseptal accentuation, scattered fibroblast foci and microscopic honeycomb change. In addition there were prominent multifocal lymphoplasmacytic infiltrates with a marked increase of IgG4-positive plasma cells (79 per high power field in hot spots) and high IgG4/IgG ratio (up to 67%). The serum IgG4 level was elevated at 760 mg/dl (reference range 9-89), with normal levels for the other IgG subclasses and negative serologic markers for autoimmune diseases. The patient's symptoms improved significantly with oral corticosteroid treatment. PMID:27053971

  7. Passage of intact IgG from plasma to the oral cavity via crevicular fluid

    PubMed Central

    Challacombe, S. J.; Russell, M. W.; Hawkes, Jane

    1978-01-01

    The aim of this investigation was to determine whether IgG could pass from the blood to the oral cavity. Pure IgG was prepared from monkey serum, by ion exchange chromatography and gel filtration, and was radiolabelled with 125I. This was injected intravenously into eight Rhesus monkeys. Radioactivity could be detected in crevicular fluid washings, and in mixed and parotid saliva samples 30 min after injection. Ultracentrifugation on sucrose density gradients revealed that most of the radioactivity in crevicular fluid washings was associated with proteins having a sedimentation coefficient similar to marker IgG. Radioactivity in parotid saliva was not found in the IgG zone, but was present in zones with sedimentation coefficients of approximately 4·5S and 1S. The results suggest that IgG passes as an intact molecule from plasma to crevicular fluid, and support the hypothesis that serum antibodies could play a role in protection against dental caries. PMID:105828

  8. Regulation of in vitro PWM-induced IgG secretion in humans

    SciTech Connect

    O'Gorman, M.R.; Oger, J.J.

    1989-02-01

    PWM-induced differentiation of human PBMC into immunoglobulin (Ig) secreting cells is a widely used model of in vivo IgG secretion. We examined the relationship between the amount of IgG secreted in PBMC cultures obtained from individuals who consistently secrete either very high (HR) or very low amounts (LR) of IgG and various in vitro immune function assays. The PBMC obtained from LR contained a higher ratio of cells expressing the T-suppressor/inducer to T-helper/inducer phenotype. The autologous mixed lymphocyte response was lower and the amount of in vivo radiation sensitive suppression was higher in the LR than in the HR. LR E- cells secreted less IgG than the HR E- cells when both were mixed with heterologous HR E+ cells. Monocyte depletion reduced IgG secretion in both LR and HR. These results suggest that each of the subsets Ts, Th (Thi, Tsi), and B lymphocytes are involved in the regulation of PWM-induced Ig secretion and that the functions of each of these subsets differ in HR and LR individuals.

  9. The antigenic and immunosuppressive properties of normal and antilymphocytic equine IgG subfractions

    PubMed Central

    Allardyce, R. A.; Anderson, N. F.; Vaerman, J. P.; James, K.

    1973-01-01

    The antigenic and immunosuppressive properties of normal and antilympho-cytic equine globulin subfractions were investigated in the rat model in an attempt to increase the efficacy of prolonged ALG therapy by limiting the immunogenic stimulus of `inactive' subfractions. Chromatographic separation of equine IgG components yielded an electro-phoretically slow gamma 2 fraction consisting of IgG2a and IgG2b and a more heterogeneous fast gamma 1 subfraction. Immunosuppression resulting from the administration of isolated subfractions was measured by the response to alum-BSA and skin allograft survival. Antigenicity was determined by a variety of immunological procedures. The immunosuppressive character of the ALG was confined to the gamma 2 fraction, however this fraction also proved antigenic in our system. The administration of normal equine IgG subfractions in combination with Freund's complete adjuvant resulted in the demonstration of antigenic differences between the fast and slow IgG components. ImagesFig. 1Fig. 2 PMID:4120853

  10. IgG4-related disease: pathophysiologic insights drive emerging treatment approaches.

    PubMed

    Stone, John H

    2016-01-01

    IgG4-related disease (IgG4-RD) is a fibroinflammatory condition that can affect essentially any organ. The disease shows similar histopathology findings across organ systems, consisting of a lymphoplasmacytic infiltrate enriched in IgG4-positive plasma cells, storiform fibrosis, and obliterative phlebitis. IgG4 itself appears to be a reactive phenomenon rather than the primary disease driver. Recent investigations have focused on the interactions between cells of the B cell lineage and a novel CD4+ SLAMF7+ cytotoxic T cells capable of promoting fibrosis. Plasmablasts appear to play a crucial role along with B cells in the presentation of antigen to this T cell. IgG4-RD is marked by responsiveness to glucocorticoids, but frequent disease relapse, the inability to taper glucocorticoids completely, and steroid toxicity are problematic. Targeted treatment approaches against the B cell lineage appear promising, and therapeutic efforts focused upon the CD4+ SLAMF7+ cytotoxic T cell may also be feasible. PMID:27586808

  11. Post-translational Modifications Differentially Affect IgG1 Conformation and Receptor Binding*

    PubMed Central

    Houde, Damian; Peng, Yucai; Berkowitz, Steven A.; Engen, John R.

    2010-01-01

    Post-translational modifications (PTMs) can have profound effects on protein structure and protein dynamics and thereby can influence protein function. To understand and connect PTM-induced functional differences with any resulting conformational changes, the conformational changes must be detected and localized to specific parts of the protein. We illustrate these principles here with a study of the functional and conformational changes that accompany modifications to a monoclonal immunoglobulin γ1 (IgG1) antibody. IgG1s are large and heterogeneous proteins capable of incorporating a multiplicity of PTMs both in vivo and in vitro. For many IgG1s, these PTMs can play a critical role in affecting conformation, biological function, and the ability of the antibody to initiate a potential adverse biological response. We investigated the impact of differential galactosylation, methionine oxidation, and fucosylation on solution conformation using hydrogen/deuterium exchange mass spectrometry and probed the effects of IgG1 binding to the FcγRIIIa receptor. The results showed that methionine oxidation and galactosylation both impact IgG1 conformation, whereas fucosylation appears to have little or no impact to the conformation. FcγRIIIa binding was strongly influenced by both the glycan structure/composition (namely galactose and fucose) and conformational changes that were induced by some of the modifications. PMID:20103567

  12. Deoxyribonuclease activity of polyclonal IgGs: a putative serological marker in patients with spondyloarthritides.

    PubMed

    Kundzer, Alena V; Volkova, Margarita V; Bogdanos, Dimitrios P; Rödiger, Stefan; Schierack, Peter; Generalov, I; Nevinsky, Georgy A; Roggenbuck, Dirk

    2013-07-01

    Antibodies executing catalytic activity are referred to as antibody enzymes or short "abzymes" and may have diagnostic relevance. Abzymes with deoxyribonuclease (DNase) activity have been demonstrated in patients with autoimmune and infectious diseases. Despite several reports on the occurrence of DNase abzymes in systemic autoimmune rheumatic diseases, conclusive data about DNase activity of antibodies in patients with spondyloarthritides (SpAs) are lacking. In recent cross-sectional studies evaluating levels of IgG DNase activity in patients with psoriatic arthritis (PsA), reactive arthritis (ReA), and ankylosing spondylitis (AS), DNase activity of IgG has been assessed by the rivanol clot method and confirmed by agarose gel electrophoresis. Remarkably, levels of IgG DNase activity were significantly higher in sera of SpA patients than those in control subjects. In patients with PsA, ReA, and AS, a positive correlation of DNase IgG activity with synovitis, disease activity, and stage of spondylitis was observed, respectively. Given the involvement of autoimmune reactions in cytolysis and connective tissue degradation in PsA, ReA, and to a lesser extent in AS, abzymes might have an impact on the pathophysiology of SpAs. Detection of IgG DNase activity in patients suffering from SpA represents an exciting new research field and may assist in the differential diagnosis of SpA. PMID:23592052

  13. IgG4-Related Lung Disease Associated with Usual Interstitial Pneumonia

    PubMed Central

    Schneider, Frank; Veraldi, Kristen L.; Levesque, Marc C.; Colby, Thomas V.; S. Yi, Eunhee

    2016-01-01

    We report a case of immunoglobulin(Ig)G4-related disease with the radiologic and histopathological manifestations resembling usual interstitial pneumonia (UIP). The patient was a 62-year-old man who presented with progressive dyspnea of insidious onset. High resolution computed tomography of the chest showed lower-lobe predominant peripheral reticulation and traction bronchiectasis but no honeycomb change. Microscopic examination of the surgical lung biopsy showed characteristic features of UIP including architectural distortion by fibrosis with peripheral and paraseptal accentuation, scattered fibroblast foci and microscopic honeycomb change. In addition there were prominent multifocal lymphoplasmacytic infiltrates with a marked increase of IgG4-positive plasma cells (79 per high power field in hot spots) and high IgG4/IgG ratio (up to 67%). The serum IgG4 level was elevated at 760 mg/dl (reference range 9-89), with normal levels for the other IgG subclasses and negative serologic markers for autoimmune diseases. The patient’s symptoms improved significantly with oral corticosteroid treatment. PMID:27053971

  14. Label-free Raman mapping of surface distribution of protein a and IgG biomolecules.

    PubMed

    Combs, Zachary A; Chang, Sehoon; Clark, Tolecia; Singamaneni, Srikanth; Anderson, Kyle D; Tsukruk, Vladimir V

    2011-03-15

    We have demonstrated a nanoengineered substrate composed of micropatterned silver nanoparticles to be used for the label-free mapping of adsorbed biomolecules. We utilized surface-enhanced Raman scattering (SERS) phenomenon to monitor the known bioanalytes, protein A and human immunoglobulin G (IgG). The SERS substrate was composed of a poly(alylamine hydrochloride) (PAH)/poly(styrenesulfonate) (PSS) layer-by-layer (LbL) nanocoating micropatterned with silver nanoparticles confined to microscopic stripes. Selective adsorption of biomacromolecules is facilitated by the amine-terminated LbL nanocoating, which prevents the surface adsorption of positively charged protein A across the surface except on the patterned regions containing negatively charged silver nanoparticles. Furthermore, adsorption of IgG on predetermined regions is facilitated by the selective binding of the Fc region of IgG to protein A. This label-free SERS approach provides accurate, selective, and fast detection of protein A and IgG solutions with a nanomolar concentration, down to below 1 nM for IgG in solution. This method could also be utilized for the facile detection of proteins in field conditions as well as in clinical, forensic, industrial, and environmental laboratories. PMID:21294559

  15. Characterization of the Rabbit Neonatal Fc Receptor (FcRn) and Analyzing the Immunophenotype of the Transgenic Rabbits That Overexpresses FcRn

    PubMed Central

    Catunda Lemos, Ana Paula; Cervenak, Judit; Bender, Balázs; Hoffmann, Orsolya Ivett; Baranyi, Mária; Kerekes, Andrea; Farkas, Anita; Bősze, Zsuzsanna; Hiripi, László; Kacskovics, Imre

    2012-01-01

    The neonatal Fc receptor (FcRn) regulates IgG and albumin homeostasis, mediates maternal IgG transport, takes an active role in phagocytosis, and delivers antigen for presentation. We have previously shown that overexpression of FcRn in transgenic mice significantly improves the humoral immune response. Because rabbits are an important source of polyclonal and monoclonal antibodies, adaptation of our FcRn overexpression technology in this species would bring significant advantages. We cloned the full length cDNA of the rabbit FcRn alpha-chain and found that it is similar to its orthologous analyzed so far. The rabbit FcRn - IgG contact residues are highly conserved, and based on this we predicted pH dependent interaction, which we confirmed by analyzing the pH dependent binding of FcRn to rabbit IgG using yolk sac lysates of rabbit fetuses by Western blot. Using immunohistochemistry, we detected strong FcRn staining in the endodermal cells of the rabbit yolk sac membrane, while the placental trophoblast cells and amnion showed no FcRn staining. Then, using BAC transgenesis we generated transgenic rabbits carrying and overexpressing a 110 kb rabbit genomic fragment encoding the FcRn. These transgenic rabbits – having one extra copy of the FcRn when hemizygous and two extra copies when homozygous - showed improved IgG protection and an augmented humoral immune response when immunized with a variety of different antigens. Our results in these transgenic rabbits demonstrate an increased immune response, similar to what we described in mice, indicating that FcRn overexpression brings significant advantages for the production of polyclonal and monoclonal antibodies. PMID:22247762

  16. Neonatal mortality: an invisible and marginalised trauma

    PubMed Central

    Målqvist, Mats

    2011-01-01

    Neonatal mortality is a major health problem in low and middle income countries and the rate of improvement of newborn survival is slow. This article is a review of the PhD thesis by Mats Målqvist, titled ‘Who can save the unseen – Studies on neonatal mortality in Quang Ninh province, Vietnam,’ from Uppsala University. The thesis aims to investigate structural barriers to newborn health improvements and determinants of neonatal death. The findings reveal a severe under-reporting of neonatal deaths in the official health statistics in Quang Ninh province in northern Vietnam. The neonatal mortality rate (NMR) found was four times higher than what was reported to the Ministry of Health. This underestimation of the problem inhibits adequate interventions and efforts to improve the survival of newborns and highlights the invisibility of this vulnerable group. The findings of the thesis also point at an inequity in survival chances based on ethnicity of the mother. Newborns of ethnic minority mothers were at a twofold risk of dying within the first 4 weeks of life compared to their peers belonging to the hegemonic group of Kinh (OR 2.08, 95% CI: 1.39–3.10). This increased risk was independent of maternal education and household economic status. Neonatal mortality was also associated with home deliveries, non-attendance to antenatal care and distance to the health care facilities. However, ethnic minority mothers still had an increased risk of experiencing a neonatal death even if they attended antenatal care, delivered at, or lived close to a health facility. This example of ethnic inequity highlights the importance to target those most in need. PMID:21423597

  17. Umbilical cord leptin predicts neonatal bone mass.

    PubMed

    Javaid, M K; Godfrey, K M; Taylor, P; Robinson, S M; Crozier, S R; Dennison, E M; Robinson, J S; Breier, B R; Arden, N K; Cooper, C

    2005-05-01

    Evidence is accumulating that the risk of osteoporosis in later life may be determined in part by environmental influences on bone development during intrauterine and early postnatal life. A potential role for fetal leptin in mediating these effects is suggested by animal studies showing that leptin influences prenatal osteoblast growth and development, and that fetal leptin concentrations are altered by changes in maternal nutrition. In a group of term human infants we reported previously that maternal birthweight, smoking, fat mass, and exercise during late pregnancy independently predict neonatal bone mass. To investigate the potential role of leptin in mediating these effects, we now relate leptin concentrations in umbilical venous serum to neonatal bone mass and body composition in 117 infants. There were strong positive associations between umbilical venous leptin concentration and each of whole body bone mineral contents (BMC) (r = 0.42, P < or = 0.001) and estimated volumetric bone density (r = 0.21, P = 0.02); whole body lean mass (r = 0.21, P < or = 0.024); and whole body fat mass (r = 0.60, P < 0.001). The associations with neonatal BMC and fat mass, but not with lean mass, were independent of associations that we have reported previously between cord serum insulin-like growth factor 1 (IGF-1) concentrations and neonatal body composition. Among the maternal determinants of neonatal bone mass, cord leptin explained the relationship with maternal fat stores, but not those with the mother's own birthweight, smoking, or physical activity. We conclude that umbilical venous leptin predicts both the size of the neonatal skeleton and its estimated volumetric mineral density. In addition, among previously documented maternal determinants of neonatal bone mass in healthy pregnancies, maternal fat stores may mediate their effect on fetal bone accrual through variation in fetal leptin concentrations. PMID:15864467

  18. How to manage neonatal tuberculosis.

    PubMed

    Di Comite, A; Esposito, S; Villani, A; Stronati, M

    2016-02-01

    This article reports the recommendations for managing neonatal tuberculosis (TB) drawn up by a group of Italian scientific societies. The Consensus Conference method was used, and relevant publications in English were identified through a systematic review of MEDLINE and the Cochrane Database of Systematic Reviews from their inception until 31 December 2014. Group experts concluded that if suspicion is aroused, it is necessary to undertake promptly all of the investigations useful for identifying the disease not only in the newborn, but also in the mother and family contacts because a diagnosis of TB in the family nucleus can guide its diagnosis and treatment in the newborn. If the suspicion is confirmed, empirical treatment should be started. Breast-fed newborns being treated with isoniazid should be given pyridoxine supplementation at a dose of 1 mg kg(-1) day(-1). Mothers with active-phase TB can breast-feed once they have become smear negative after having received appropriate treatment. PMID:26270256

  19. Advances in Neonatal Pulmonary Hypertension.

    PubMed

    Steinhorn, Robin H

    2016-01-01

    Persistent pulmonary hypertension of the newborn (PPHN) is a surprisingly common event in the neonatal intensive care unit, and affects both term and preterm infants. Recent studies have begun to elucidate the maternal, fetal and genetic risk factors that trigger PPHN. There have been numerous therapeutic advances over the last decade. It is now appreciated that oxygen supplementation, particularly for the goal of pulmonary vasodilation, needs to be approached as a therapy that has risks and benefits. Administration of surfactant or inhaled nitric oxide (iNO) therapy at a lower acuity of illness can decrease the risk of extracorporeal membrane oxygenation/death, progression of disease and duration of hospital stay. Milrinone may have specific benefits as an 'inodilator', as prolonged exposure to iNO plus oxygen may activate phosphodiesterase (PDE) 3A. Additionally, sildenafil and hydrocortisone may benefit infants exposed to hyperoxia and oxidative stress. Continued investigation is likely to reveal new therapies such as citrulline and cinaciguat that will enhance NO synthase and soluble guanylate cyclase function. Continued laboratory and clinical investigation will be needed to optimize treatment and improve outcomes. PMID:27251312

  20. Nesidioblastosis and persistent neonatal hyperinsulinism.

    PubMed

    Sempoux, C; Poggi, F; Brunelle, F; Saudubray, J M; Fekete, C; Rahier, J

    1995-12-01

    Neonatal hyperinsulinism is characterized by severe hypoglycaemia which can cause serious neurologic effects. Pancreatic morphological abnormalities involve either focal or diffuse lesions. The former can be cured by resection, whereas the latter, of uncertain pathogenesis, often require subtotal pancreatectomy. We investigated various hypotheses in an effort to explain the origin of this latter form of hyperinsulinism. We determined that nesidioblastosis, long considered to be the basic structural lesion of the diffuse form of hyperinsulinism, is not specific and does not correspond to a continuous proliferation of endocrine cells. We found that an increase in beta-cell mass can be excluded since the volume density of beta cells is not systematically higher in hyperinsulinemic infants than in controls. The hypothesis of a decrease in D cells is attractive but should be considered with due caution since the decrease of the D-cell volume density observed in hypoglycaemic infants is inconstant. Finally, the notion of beta-cell functional abnormality seems the most likely explanation since a higher quantity of proinsulin was detected within the Golgi area by a specific antibody and abnormal nuclei with abundant cytoplasm were observed in some cells. These histological abnormalities can be observed during intraoperative morphological examination. Functional activity might also be evaluated by studying the messenger RNA of proinsulin. PMID:8593920

  1. Olfactory Classical Conditioning in Neonates

    PubMed Central

    Sullivan, Regina M.; Taborsky-Barba, Suzanne; Mendoza, Raffael; Itano, Alison; Leon, Michael; Cotman, Carl W.; Payne, Terrence F.; Lott, Ira

    2007-01-01

    One-day-old, awake infants underwent an olfactory classical conditioning procedure to assess associative learning within the olfactory system of newborns. Experimental infants received ten 30-second pairings of a novel olfactory conditioned stimulus (a citrus odor of neutral value) and tactile stimulation provided by stroking as the reinforcing unconditioned stimulus (a stimulus with positive properties). Control babies received only the odor, only the stroking, or the stroking followed by the odor presentation. The next day, all infants, in either the awake or sleep state, were given five 30-second presentations of the odor. Results were analyzed from video tapes scored by an observer unaware of the infants’ training condition. The results indicate that only those infants who received the forward pairings of the odor and stroking exhibited conditioned responding (head turning toward the odor) to the citrus odor. The performance of the conditioned response was not affected by the state of the baby during testing, because both awake and sleeping infants exhibited conditioned responses. Furthermore, the expression of the conditioned response was odor specific; a novel floral odor presented during testing did not elicit conditioned responses in the experimental babies. These results suggest that complex associative olfactory learning is seen in newborns within the first 48 hours of life. These baseline findings may serve as normative data against which observation from neonates at risk for neurological sequelae may be compared. PMID:2011429

  2. Transport of the subclasses of human IgG across the yolk-sac of the foetal rabbit

    PubMed Central

    Hemmings, W. A.

    1974-01-01

    The four subclasses of human IgG were labelled either with 125I or 131I and injected into rabbit uteri (24 days pregnant) in pairs. Transmission to the foetal circulation was measured 1 day later. It was found that all four sub-classes are transmitted, though IgG1 enters most readily. Whole labelled human IgG fast and slow electrophoretic fractions prepared by DEAE chromatography were also injected and an isoelectrofocusing analysis carried out on the injected IgG and the foetal serum. There was considerable variation of transmission even between adjacent peaks of the IEF pattern. PMID:4435834

  3. Serosal involvement in IgG4-related disease: report of two cases and review of the literature.

    PubMed

    González-Moreno, Juan; Losada-López, Inés; Gállego-Lezaun, Cristina; García-Gasalla, Mercedes; Gómez Bellvert, Cristina; Ortego Centeno, Norberto

    2016-07-01

    IgG4-related disease (IgG4-RD) is a recently described entity characterized by lymphoplasmacytic infiltrates, usually mimicking tumors, affecting almost every organ or system. Nevertheless, serosal involvement has been rarely reported. In this article, we report two cases of IgG4-RD with serosal involvement and review the literature. Because of the varied clinical pictures found in our review, we suggest a new terminology for the description of IgG4-RD with serosal involvement. PMID:27207156

  4. Conformation of human IgG subclasses in solution. Small-angle X-ray scattering and hydrodynamic studies.

    PubMed

    Kilár, F; Simon, I; Lakatos, S; Vonderviszt, F; Medgyesi, G A; Závodszky, P

    1985-02-15

    The structure of six human myeloma proteins: IgG1(Bal), IgG2(Klu), IgG3(Bak), IgG3(Het), IgG4(Kov) and IgG4(Pol), was studied in solution using small-angle X-ray scattering and hydrodynamic methods. For IgG1(Bal) and IgG3(Het) the experimental data, including radius of gyration (Rg degree), radii of gyration of the cross-section (Rq1, Rq2), intrinsic viscosity [eta], sedimentation coefficient (S degree 20,w) and molecular mass, were interpreted in terms of structural models based on the Fab and Fc conformations, observed in crystal, by varying the relative positions of the Fab and Fc parts, i.e. their relative angles and distances. The values Rg degree = (6.00 +/- 0.05) nm, S degree 20,w = (6.81 +/- 0.10) S and [eta] = 0.0062 +/- 0.0005 cm3/mg obtained for IgG1(Bal) are compatible with a planar model in which the angle between the Fab arms is about 120 degrees. For IgG3(Het) the following data were obtained: Rg degree = (4.90 +/- 0.05) nm, S degree 20,w = (6.32 +/- 0.01) S and [eta] = (0.0065 +/- 0.0005) cm3/mg. The apparent contradiction between the higher molecular mass and lower Rg degree and S degree 20,w values for IgG3(Het) in comparison to IgG1(Bal) can be resolved by proposing a 'non-planar' (tetrahedral) molecular shape, in which the long hinge peptide is in a folded conformation and the two Fab and Fc parts are in a closely packed arrangement. In this model the angle between the two Fab arms is about 90 degrees, in the average position. The X-ray scattering and hydrodynamic behaviour of the IgG2 and IgG4 types of antibodies appeared to be similar to IgG1(Bal). The parameters of the two IgG3 proteins are similar while they are different to the others. PMID:3971974

  5. Schnitzler's syndrome with monoclonal IgG kappa gammopathy: good response to cyclosporin.

    PubMed

    Pascual-López, M; Hernández-Núñez, A; Sánchez-Pérez, J; Fernández-Herrera, J; García-Díez, A

    2002-05-01

    Schnitzler's syndrome (SS) is a rare entity characterized by the association of chronic urticaria and monoclonal IgM gammopathy. Usually, intermittent fever, arthralgia and elevation of erythrocyte sedimentation rate also occur. We report a patient with the same symptoms, but with monoclonal IgG instead of IgM paraproteinaemia. Histological examination of the urticarial lesions showed signs of leucocytoclastic vasculitis. After 20 years of therapeutic failure, cyclosporin has achieved a total clearance of urticarial lesions in our patient. Two previous similar cases with clinical features of SS and monoclonal IgG immunoglobulin have been described. We suggest our case also represents a variant of SS with IgG gammopathy. PMID:12195569

  6. Extracorporeal immunoadsorption of myeloma IgG and autoimmune antibodies: a clinically feasible modality of treatment.

    PubMed Central

    Ray, P K; Besa, E; Idiculla, A; Rhoads, J E; Bassett, J G; Cooper, D R

    1980-01-01

    Using heat-killed, formalin-stabilized Staphylococcus aureus Cowan I suspension, it was possible to remove myeloma IgG and autoimmune anti-red blood cell antibodies from two patients' plasma following an extracorporeal procedure. The arterial anticoagulated blood was processed through a cell separator machine. The separated plasma was pumped through a bacterial filter containing S. aureus suspension. The adsorbed plasma was then reunited with the blood cells and returned to the patient through the vein. S. aureus Cowan I could selectively remove the myeloma IgG and autoimmune anti-red cell antibodies from the patients' plasma prolonging the lives of these two terminal patients. The immunoadsorption procedure appears to be a safe, practical and quick method for the removal of pathological IgG from the patients' plasma. PMID:7008987

  7. Computational design of a pH-sensitive IgG binding protein.

    PubMed

    Strauch, Eva-Maria; Fleishman, Sarel J; Baker, David

    2014-01-14

    Computational design provides the opportunity to program protein-protein interactions for desired applications. We used de novo protein interface design to generate a pH-dependent Fc domain binding protein that buries immunoglobulin G (IgG) His-433. Using next-generation sequencing of naïve and selected pools of a library of design variants, we generated a molecular footprint of the designed binding surface, confirming the binding mode and guiding further optimization of the balance between affinity and pH sensitivity. In biolayer interferometry experiments, the optimized design binds IgG with a Kd of ∼ 4 nM at pH 8.2, and approximately 500-fold more weakly at pH 5.5. The protein is extremely stable, heat-resistant and highly expressed in bacteria, and allows pH-based control of binding for IgG affinity purification and diagnostic devices. PMID:24381156

  8. Global and Local Conformation of Human IgG Antibody Variants Rationalizes Loss of Thermodynamic Stability.

    PubMed

    Edgeworth, Matthew J; Phillips, Jonathan J; Lowe, David C; Kippen, Alistair D; Higazi, Daniel R; Scrivens, James H

    2015-12-01

    Immunoglobulin G (IgG) monoclonal antibodies (mAbs) are a major class of medicines, with high specificity and affinity towards targets spanning many disease areas. The antibody Fc (fragment crystallizable) region is a vital component of existing antibody therapeutics, as well as many next generation biologic medicines. Thermodynamic stability is a critical property for the development of stable and effective therapeutic proteins. Herein, a combination of ion-mobility mass spectrometry (IM-MS) and hydrogen/deuterium exchange mass spectrometry (HDX-MS) approaches have been used to inform on the global and local conformation and dynamics of engineered IgG Fc variants with reduced thermodynamic stability. The changes in conformation and dynamics have been correlated with their thermodynamic stability to better understand the destabilising effect of functional IgG Fc mutations and to inform engineering of future therapeutic proteins. PMID:26482340

  9. Human IgG detection in serum on polymer based Mach-Zehnder interferometric biosensors.

    PubMed

    Melnik, Eva; Bruck, Roman; Müellner, Paul; Schlederer, Thomas; Hainberger, Rainer; Lämmerhofer, Michael

    2016-03-01

    We report a new method for detecting human IgG (hIgG) in serum on integrated-optical Mach-Zehnder interferometer biosensors realized in a high index contrast polymer material system. In the linear range of the sensor (5-200 nM) we observed excellent signal recoveries (95-110%) in buffer and serum samples, which indicate the absence of matrix effects. Signal enhancement was reached by using secondary anti-human IgG antibodies, which bind to immobilized target IgGs and allow detecting concentrations down to 100 pM. This polymer based optical sensor is fully compatible with cost-efficient mass production technologies, which makes it an attractive alternative to inorganic optical sensors. Graphical abstract of the hIgG measured on polymer based photonic sensors using a direct binding assay and a signal enhancement strategy with secondary antibodies. PMID:26663736

  10. Contactin 1 IgG4 associates to chronic inflammatory demyelinating polyneuropathy with sensory ataxia

    PubMed Central

    Miura, Yumako; Devaux, Jérôme J.; Fukami, Yuki; Manso, Constance; Belghazi, Maya; Wong, Anna Hiu Yi

    2015-01-01

    A Spanish group recently reported that four patients with chronic inflammatory demyelinating polyneuropathy carrying IgG4 autoantibodies against contactin 1 showed aggressive symptom onset and poor response to intravenous immunoglobulin. We aimed to describe the clinical and serological features of Japanese chronic inflammatory demyelinating polyneuropathy patients displaying the anti-contactin 1 antibodies. Thirteen of 533 (2.4%) patients with chronic inflammatory demyelinating polyneuropathy had anti-contactin 1 IgG4 whereas neither patients from disease or normal control subjects did (P = 0.02). Three of 13 (23%) patients showed subacute symptom onset, but all of the patients presented with sensory ataxia. Six of 10 (60%) anti-contactin 1 antibody-positive patients had poor response to intravenous immunoglobulin, whereas 8 of 11 (73%) antibody-positive patients had good response to corticosteroids. Anti-contactin 1 IgG4 antibodies are a possible biomarker to guide treatment option. PMID:25808373

  11. [IgG4-related disease treatment in 2014: Update and literature review].

    PubMed

    Grados, A; Ebbo, M; Jean, E; Bernit, E; Harlé, J-R; Schleinitz, N

    2015-06-01

    IgG4-related disease is an inflammatory disorder characterized by a polyclonal lymphoplasmacytic tissue infiltrate, with numerous IgG4+ plasmocytes, evolving toward fibrosis. The disease is heterogeneous and affects several tissues and organs synchroneously or metachroneously. Both the fibrosis and the tumor forming characteristics of the disease can be responsible of irreversible tissue damage. For these reasons treatment is usually necessary. A dramatic response is usually observed with steroid treatment but relapses are frequent. Immunosuppressive agents and rituximab are used as second line treatments. We review here previous studies on treatment and suggest general recommendations for the treatment and follow up of patients with IgG4-related disease. PMID:25595874

  12. [Monoclonal human immunoglobulin (IgG lambda) with antiethinylestradiol activity, oral contraceptives, and arterial pulmonary thrombosis].

    PubMed

    Beaumont, J L; Lemort, N

    1975-06-23

    In a 36-year-old woman taking an oral contraceptive containing 50 mug of ethinyloestradiol each day, a pulmonary arterial thrombosis and a monoclonal gammapathia were associated. The monoclonal IgI lambda Mai... was prepared. When purified, this IgG lambda binds ethinyloestradiol with strong affinity (Ka= 2.7 times 10(7)M-1) and also 17-beta-oestradiol with a little less affinity (Ka = 0.4 times 10(7)M-1. For those ligands each IgG lambda Mai... molecule has two sites of same affinity and specificity so that a Scatchard plot of the experimental values gives a straight line. It is likely that the antibody sites of the IgG lambda Mai... are the binding sites. These facts support the hypothesis of an immunological mechanism of the thromboembolic disease which may be induced by oral contraceptives. PMID:808320

  13. Voltage-driven translocation behaviors of IgG molecule through nanopore arrays

    PubMed Central

    2013-01-01

    Nanopore-based biosensing has attracted more and more interests in the past years, which is also regarded as an emerging field with major impact on bio-analysis and fundamental understanding of nanoscale interactions down to single-molecule level. In this work, the voltage-driven translocation properties of goat antibody to human immunoglobulin G (IgG) are investigated using nanopore arrays in polycarbonate membranes. Obviously, the background ionic currents are modulated by IgG molecules for their physical place-holding effect. However, the detected ionic currents do ‘not’ continuously decrease as conceived; the currents first decrease, then increase, and finally stabilize with increasing IgG concentration. To understand this phenomenon, a simplified model is suggested, and the calculated results contribute to the understanding of the abnormal phenomenon in the actual ionic current changing tendency. PMID:23676116

  14. Imaging of inflammatory arthritis with technetium-99m-labeled IgG

    SciTech Connect

    Breedveld, F.C.; van Kroonenburgh, M.J.; Camps, J.A.; Feitsma, H.I.; Markusse, H.M.; Pauwels, E.K. )

    1989-12-01

    The accumulation of nonspecific polyclonal human immunoglobulin G (IgG) radiolabeled with 99mTc was compared to that of (99mTc)albumin and (99mTc)nanocolloid in rats with collagen induced arthritis. Serial scintigrams were acquired directly, 4 and 24 hr after injection. A clearly discernable image of the site of synovitis was seen with (99mTc)IgG as early as 4 hr postinjection. The relative intensity of the inflammatory lesion was maximal at 24 hr. Discrimination between arthritic and nonarthritic joints as well as correlations between the relative intensity of the arthritic joint and clinical indices of joint inflammation were superior with IgG compared to albumin or nanocolloid. These studies show that localization and severity of inflammatory joint disease can be detected with radiolabeled nonspecific IgG.

  15. The many faces of Merlin: IgG4-associated pulmonary-renal disease.

    PubMed

    Sprangers, Ben; Lioen, Pieter; Meijers, Björn; Lerut, Evelyne; Meersschaert, Joke; Blockmans, Daniel; Claes, Kathleen

    2011-09-01

    Pulmonary-renal syndrome is a common and serious disorder with a broad differential diagnosis. We describe a case of a middle-aged man presenting with interstitial pulmonary disease and severe renal impairment caused by a hypocomplementemic immune-complex-mediated interstitial nephritis. Serum levels of IgG4 were elevated, and renal biopsy specimens revealed the presence of interstitial IgG4(+) plasma cells. There was a rapid improvement of both pulmonary and renal abnormalities after the initiation of corticosteroids. To our knowledge, this report is the first to show interstitial pulmonary disease in association with interstitial kidney disease as the predominant and presenting symptoms of IgG4-related disease. PMID:21896524

  16. Voltage-driven translocation behaviors of IgG molecule through nanopore arrays

    NASA Astrophysics Data System (ADS)

    Liu, Lei; Wang, Bing; Sha, Jingjie; Yang, Yue; Hou, Yaozong; Ni, Zhonghua; Chen, Yunfei

    2013-05-01

    Nanopore-based biosensing has attracted more and more interests in the past years, which is also regarded as an emerging field with major impact on bio-analysis and fundamental understanding of nanoscale interactions down to single-molecule level. In this work, the voltage-driven translocation properties of goat antibody to human immunoglobulin G (IgG) are investigated using nanopore arrays in polycarbonate membranes. Obviously, the background ionic currents are modulated by IgG molecules for their physical place-holding effect. However, the detected ionic currents do `not' continuously decrease as conceived; the currents first decrease, then increase, and finally stabilize with increasing IgG concentration. To understand this phenomenon, a simplified model is suggested, and the calculated results contribute to the understanding of the abnormal phenomenon in the actual ionic current changing tendency.

  17. Detection of histidine oxidation in a monoclonal immunoglobulin gamma (IgG) 1 antibody.

    PubMed

    Amano, Masato; Kobayashi, Naoki; Yabuta, Masayuki; Uchiyama, Susumu; Fukui, Kiichi

    2014-08-01

    Although oxidation of methionine and tryptophan are known as popular chemical modifications that occur in monoclonal antibody (mAb) molecules, oxidation of other amino acids in mAbs has not been reported to date. In this study, oxidation of the histidine residue in a human immunoglobulin gamma (IgG) 1 molecule was discovered for the first time by mass spectrometry. The oxidation of a specific histidine located at the CH2 domain of IgG1 occurred under light stress, but it was not observed under heat stress. With the forced degradation study using several reactive oxygen species, the singlet oxygen was attributed to a reactive source of the histidine oxidation. The reaction mechanism of the histidine oxidation was proposed on the basis of the mass spectrometric analysis of IgG1 oxidized in deuterium oxide and hydrogen heavy oxide. PMID:24940720

  18. Computational design of a pH-sensitive IgG binding protein

    PubMed Central

    Strauch, Eva-Maria; Fleishman, Sarel J.; Baker, David

    2014-01-01

    Computational design provides the opportunity to program protein–protein interactions for desired applications. We used de novo protein interface design to generate a pH-dependent Fc domain binding protein that buries immunoglobulin G (IgG) His-433. Using next-generation sequencing of naïve and selected pools of a library of design variants, we generated a molecular footprint of the designed binding surface, confirming the binding mode and guiding further optimization of the balance between affinity and pH sensitivity. In biolayer interferometry experiments, the optimized design binds IgG with a Kd of ∼4 nM at pH 8.2, and approximately 500-fold more weakly at pH 5.5. The protein is extremely stable, heat-resistant and highly expressed in bacteria, and allows pH-based control of binding for IgG affinity purification and diagnostic devices. PMID:24381156

  19. Seroprevalence of IgG1 and IgG4 class antibodies against Mycobacterium avium subsp. paratuberculosis in Japanese population.

    PubMed

    Otsubo, Shigeru; Cossu, Davide; Eda, Shigetoshi; Otsubo, Yuriko; Sechi, Leonardo Antonio; Suzuki, Tsuyoshi; Iwao, Yumiko; Yamamoto, Shizuo; Kuribayashi, Takashi; Momotani, Eiichi

    2015-10-01

    Mycobacterium avium subsp. paratuberculosis (MAP) is the established causative agent of Johne's disease in cattle and other ruminants, and it has also been speculated to be a putative etiological agent of several human autoimmune diseases. It is acknowledged that dairy products deriving from infected animals play a role (could be vehicles) in exposing humans to MAP. MAP could stimulate the human immune system by means of their complex antigen (in the case of lipids, multivalent antigens) and may modulate it, acting as adjuvant molecules such as Freund's complete adjuvant. The immune system might be abnormally stimulated by the constant presence of MAP antigens (for example, in the dairy products), and this might be particularly relevant in genetically predisposed individuals. However, there is limited understanding about the current human exposure to MAP. The present study analyzed the antibody recognition profile of MAP lipophilic antigens in a cohort of 126 healthy Japanese. We measured the serum levels of total immunoglobulin G (IgG) and subclasses targeting MAP surface antigens through ethanol vortex indirect enzyme-linked immunosorbent assay (EVELISA) by using serum absorbed with Mycobacterium phlei. Elevated IgG (especially IgG1 and IgG4) responses were observed in 14% of the sera. To assess the specificity of EVELISA, the same samples were analyzed by means of a commercially available Johnelisa II kit. It was noteworthy that a high degree of correlation was observed when comparing the two methodologies (rs=0.7, p<0.0001). Moreover, in order to investigate the specificity of the binding, inhibition assay experiments were carried out also searching for antibodies against Bacillus Calmette-Guérin antigens, but no cross-reaction was observed. The result obtained represents the first evidence implying that the Japanese population is exposed to MAP, and additionally the existence of a foodborne chain of exposure that transmits MAP antigens to humans. PMID

  20. Lactoferrin for prevention of neonatal sepsis

    PubMed Central

    Turin, Christie G.; Zea-Vera, Alonso; Pezo, Alonso; Cruz, Karen; Zegarra, Jaime; Bellomo, Sicilia; Cam, Luis; Llanos, Raul; Castañeda, Anne; Tucto, Lourdes; Ochoa, Theresa J.

    2015-01-01

    Preterm neonates are at risk to acquire infections. In addition to the high mortality associated with sepsis, these patients are at risk for long-term disabilities, particularly neurodevelopment impairment. Several interventions have been evaluated to reduce rates of infections in neonates but have not proven efficacy. Lactoferrin (LF), a milk glycoprotein with anti-inflammatory, immunomodulatory and anti-microbial properties, has the potential to prevent infections in young children. We performed a review of current and ongoing clinical trials of LF for prevention of neonatal sepsis, and found eleven registered clinical trials that include more than 6000 subjects. Few of these trials have finished; despite their small sample size, the preliminary results show a trend towards a positive protective effect of LF on neonatal infections. Larger trials are underway to confirm the findings of these initial studies. This information will help to define LF´s role in clinical settings and, if proven effective, would profoundly affect the treatment of low birth weight neonates as a cost-effective intervention worldwide. PMID:24935001

  1. Antimicrobial therapy in neonatal intensive care unit.

    PubMed

    Tzialla, Chryssoula; Borghesi, Alessandro; Serra, Gregorio; Stronati, Mauro; Corsello, Giovanni

    2015-01-01

    Severe infections represent the main cause of neonatal mortality accounting for more than one million neonatal deaths worldwide every year. Antibiotics are the most commonly prescribed medications in neonatal intensive care units (NICUs) and in industrialized countries about 1% of neonates are exposed to antibiotic therapy. Sepsis has often nonspecific signs and symptoms and empiric antimicrobial therapy is promptly initiated in high risk of sepsis or symptomatic infants. However continued use of empiric broad-spectrum antibiotic treatment in the setting of negative cultures especially in preterm infants may not be harmless.The benefits of antibiotic therapy when indicated are clearly enormous, but the continued use of antibiotics without any microbiological justification is dangerous and only leads to adverse events. The purpose of this review is to highlight the inappropriate use of antibiotics in the NICUs, to exam the impact of antibiotic treatment in preterm infants with negative cultures and to summarize existing knowledge regarding the appropriate choice of antimicrobial agents and optimal duration of therapy in neonates with suspected or culture-proven sepsis in order to prevent serious consequences. PMID:25887621

  2. Do ventilated neonates require pain management?

    PubMed

    Hall, R Whit; Boyle, Elaine; Young, Thomas

    2007-10-01

    Mechanical ventilation is a stressful experience in neonates resulting in changes in neuroendocrine parameters, pain scores, and physiologic responses. Assisted ventilation in neonates is presumed to be associated with chronic repetitive pain, which in turn is associated with adverse long-term sequelae. Reasons to routinely sedate ventilated neonates include improved ventilator synchrony, improved pulmonary function, and decreased neuroendocrine responses, including cortisol, beta-endorphine, and catecholamines. Reasons not to treat include the well-known adverse side effects of pain medication, especially the opiates, including hypotension from morphine, chest wall rigidity from fentanyl, and tolerance, dependence, and withdrawal from both opiates and benzodiazepines. Additionally, adverse effects such as death and IVH are not improved with preemptive treatment. Chronic pain assessment is poorly validated and difficult to assess in this population, and most studies have evaluated only acute pain scores. If patients are treated, opiates are the most common class of drugs, with morphine the most well studied. Fentanyl may be advantageous in hypotensive, younger neonates because it has fewer cardiovascular effects. The benzodiazepines, midazolam and lorazepam, have been used in ventilated neonates, but midazolam has been associated with adverse effects in one small study so concern remains regarding its use. Significant gaps in our knowledge exist, especially in regard to long-term effects of treatment, or lack thereof, and in the assessment of the chronic pain associated with assisted ventilation. PMID:17905183

  3. Neonatal Tracheostomy – Issues and Solutions

    PubMed Central

    A, Saadia; GR, Prasad

    2015-01-01

    Aims: To record and analyse the technical aspects of neonatal tracheostomy and to suggest some solutions. Materials and Methods: This is a retrospective observational cohort of 37 cases of neonatal tracheostomies performed over 30 years (1985-2014). Results: Thirty-three of the 37 tracheostomies were done as an elective procedure and four done emergently. Eighteen neonatal tracheostomies were done with a low transverse cervical incision and 19 were done with low vertical cervical incision. Three patients had bleeding while exposing the trachea. Trachea could not easily be identified in 2 cases. Commercial tracheostomy tubes were used in only 20 cases. In 17 patients, the conventional endotracheal tubes 2.5 or 3fr size were used. There were 3 instances of wound infection out of which one has peri-tracheostomy necrotizing cellulitis and the neonate succumbed to sepsis. Two cases had surgical emphysema. No case had pneumothorax. Conclusion: We described tracheostomy in neonates in a resource constrained centre. Various makeshift arrangements can be used in absence of standard supplies. PMID:26034707

  4. Late-onset neonatal sepsis: recent developments

    PubMed Central

    Dong, Ying; Speer, Christian P

    2015-01-01

    The incidence of neonatal late-onset sepsis (LOS) is inversely related to the degree of maturity and varies geographically from 0.61% to 14.2% among hospitalised newborns. Epidemiological data on very low birth weight infants shows that the predominant pathogens of neonatal LOS are coagulase-negative staphylococci, followed by Gram-negative bacilli and fungi. Due to the difficulties in a prompt diagnosis of LOS and LOS-associated high risk of mortality and long-term neurodevelopmental sequelae, empirical antibiotic treatment is initiated on suspicion of LOS. However, empirical therapy is often inappropriately used with unnecessary broad-spectrum antibiotics and a prolonged duration of treatment. The increasing number of multidrug-resistant Gram-negative micro-organisms in neonatal intensive care units (NICU) worldwide is a serious concern, which requires thorough and efficient surveillance strategies and appropriate treatment regimens. Immunological strategies for preventing neonatal LOS are not supported by current evidence, and approaches, such as a strict hygiene protocol and the minimisation of invasive procedures in NICUs represent the cornerstone to reduce the burden of neonatal LOS. PMID:25425653

  5. Anti-Leishmania infantum IgG Antibody Avidity in Visceral Leishmaniasis

    PubMed Central

    Tiburcio, Monique Gomes Salles; Anversa, Laís; Kanunfre, Kelly Aparecida; Ferreira, Antonio Walter; Rodrigues Júnior, Virmondes

    2013-01-01

    IgG avidity tests are used to discriminate acute from chronic infections. There are few reports on the IgG avidity profile of patients with visceral leishmaniasis (VL). This study investigated the anti-Leishmania IgG avidity in patients with classic VL (n = 10), patients showing clinical cure after treatment (n = 18), and asymptomatic subjects with at least one positive Leishmania test (n = 20). All subjects were from areas in Brazil where VL is endemic. Serum samples were collected from each subject on two different occasions. IgG avidity was evaluated by Western blotting. The proportion of high-avidity antibodies was higher in all samples from patients with classic VL. In contrast, low-avidity antibodies predominated in subjects with a history of VL, including 13 cases (72.2%) in the first assessment and 14 (77.8%) in the second. Fifteen (75%) of the asymptomatic subjects presented a predominance of low-avidity antibodies in the first assessment, and the frequency of high-avidity antibodies increased over time in seven subjects (35%) of this group. Antibodies against the 14- and/or 16-kDa antigen fraction were detected in the first assessment in all patients with classic VL, in 10 (55.5%) treated patients, and in 10 (50%) asymptomatic subjects. These were high-avidity antibodies in most cases. In the asymptomatic group, an increase in IgG avidity against the 14- and/or 16-kDa antigen fraction was observed in three cases (15%). The results indicate distinct responses in infected and asymptomatic subjects, probably associated with the length of time after infection. In this respect, IgG avidity tests represent a new approach to better characterize asymptomatic VL. PMID:24006136

  6. Profiling IgG N-glycans as potential biomarker of chronological and biological ages

    PubMed Central

    Yu, Xinwei; Wang, Youxin; Kristic, Jasminka; Dong, Jing; Chu, Xi; Ge, Siqi; Wang, Hao; Fang, Honghong; Gao, Qing; Liu, Di; Zhao, Zhongyao; Peng, Hongli; Pucic Bakovic, Maja; Wu, Lijuan; Song, Manshu; Rudan, Igor; Campbell, Harry; Lauc, Gordan; Wang, Wei

    2016-01-01

    Abstract As an important post-translation modifying process, glycosylation significantly affects the structure and function of immunoglobulin G (IgG) molecules and is essential in many steps of the inflammatory cascade. Studies have demonstrated the potential of using glycosylation features of IgG as a component of predictive biomarkers for chronological age in several European populations, whereas no study has been reported in Chinese. Herein, we report various patterns of changes in IgG glycosylation associated with age by analyzing IgG glycosylation in 701 community-based Han Chinese (244 males, 457 females; 23–68 years old). Eleven IgG glycans, including FA2B, A2G1, FA2[6]G1, FA2[3]G1, FA2[6]BG1, FA2[3]BG1, A2G2, A2BG2, FA2G2, FA2G2S1, and FA2G2S2, change considerably with age and specific combinations of these glycan features can explain 23.3% to 45.4% of the variance in chronological age in this population. This indicates that these combinations of glycan features provide more predictive information than other single markers of biological age such as telomere length. In addition, the clinical traits such as fasting plasma glucose and aspartate aminotransferase associated with biological age are strongly correlated with the combined glycan features. We conclude that IgG glycosylation appears to correlate with both chronological and biological ages, and thus its possible role in the aging process merits further study. PMID:27428197

  7. Overlapping IgG4 Responses to Self- and Environmental Antigens in Endemic Pemphigus Foliaceus.

    PubMed

    Qian, Ye; Jeong, Joseph S; Ye, Jian; Dang, Bim; Abdeladhim, Maha; Aoki, Valeria; Hans-Filhio, Gunter; Rivitti, Evandro A; Valenzuela, Jesus G; Diaz, Luis A

    2016-03-01

    The etiology of human autoimmune diseases in general remains largely unknown, although the genetic and environmental interplay may be relevant. This applies to the autoimmune diseases of the skin such as the pemphigus phenotypes and others. In this group, there is an endemic form of pemphigus foliaceus (also known as fogo selvagem [FS]) in which the pathogenic IgG4 autoantibody response to the self-antigen desmoglein 1 (Dsg1) cross-reacts with the LJM11 sand fly salivary gland Ag. In this investigation, we dissected the IgG4 autoantibody repertoires used by FS patients in response to endogenous self-Dsg1 and exogenous LJM11 sand fly Ag. Based on analyses of the genetic clonal signatures of these Abs, our results indicate that there is a significant overlap between these two responses, as all identified IgG4 mAbs cross-react to both Dsg1 and LJM11 Ags. Germline H- and L-chain V gene Abs generated according to mutated cross-reactive mAbs preserved their reactivity to both Ags. Our findings suggest that both Dsg1 autoantigen and LJM11 environmental Ag could be the initial antigenic stimulants for the IgG4 autoimmune responses in FS. These results support our hypothesis that LJM11 Ag plays a substantial role in triggering the IgG4 autoantibody development in FS and provide new insights on how noninfectious environmental Ag(s) may drive the generation of autoantibodies in IgG4-related autoimmune diseases. PMID:26826247

  8. Extraction of monoclonal antibodies (IgG1) using anionic and anionic/nonionic reverse micelles.

    PubMed

    George, Daliya A; Stuckey, David C

    2010-01-01

    Purification schemes for antibody production based on affinity chromatography are trying to keep pace with increases in cell culture expression levels and many current research initiatives are focused on finding alternatives to chromatography for the purification of Monoclonal antibodies (MAbs). In this article, we have investigated an alternative separation technique based on liquid-liquid extraction called the reverse micellar extraction. We extracted MAb (IgG1) using reverse micelles of an anionic surfactant, sodium bis 2-ethyl-hexyl sulfosuccinate (AOT) and a combination of anionic (AOT) and nonionic surfactants (Brij-30, Tween-85, Span-85) using isooctane as the solvent system. The extraction efficiency of IgG1 was studied by varying parameters, such as pH of the aqueous phase, cation concentration, and type and surfactant concentration. Using the AOT/Isooctane reverse micellar system, we could achieve good overall extraction of IgG1 (between 80 and 90%), but only 30% of the bioactivity of IgG1 could be recovered at the end of the extraction by using its binding to affinity chromatography columns as a surrogate measure of activity. As anionic surfactants were suspected as being one of the reasons for the reduced activity, we decided to combine a nonionic surfactant with an anionic surfactant and then study its effect on the extraction efficiency and bioactivity. The best results were obtained using an AOT/Brij-30/Isooctane reverse micellar system, which gave an overall extraction above 90 and 59% overall activity recovery. An AOT/Tween-85/Isooctane reverse micellar system gave an overall extraction of between 75 and 80% and overall activity recovery of around 40-45%. The results showed that the activity recovery of IgG1 can be significantly enhanced using different surfactant combination systems, and if the recovery of IgG1 can be further enhanced, the technique shows considerable promise for the downstream purification of MAbs. PMID:20665658

  9. High Serum IgG4 Concentrations in Patients with Hashimoto's Thyroiditis.

    PubMed

    Popławska-Kita, Anna; Kościuszko-Zdrodowska, Maria; Siewko, Katarzyna; Telejko, Beata; Hryniewicka, Justyna; Milewski, Robert; Abdelrazek, Saeid Soleman; Szelachowska, Małgorzata; Górska, Maria

    2015-01-01

    Purpose. Since recent reports suggest that Hashimoto thyroiditis (HT) may be associated with IgG4-related disease, we aimed to find out whether the measurement of serum IgG4 allows for the identification of distinct types of HT, with different clinical, sonographic, and serologic characteristics. Methods. The group studied consisted of 53 patients with HT and 28 healthy individuals who underwent thyroid ultrasonography and body composition analysis. Serum concentrations of IgG4, TSH, anti-peroxidase antibodies (TPOAb), anti-TSH receptor antibodies, TNF-α, TGF-β1, Fas Ligand, TRAIL, and chemokines (CXCL9, CXCL11, and CXCL10) were measured by ELISA or radioimmunoassay. Results. The group with IgG4 level >135 IU/ml accounted for 32.5% of the patients. The signs of fibrosis were present in 27.0% of the high-IgG4 patients and in 9.1% of the normal-IgG4 group. The patients with elevated IgG4 required higher doses of L-thyroxine and had significantly lower level of TPOAb (P=0.02) than the non-IgG4-HT individuals and higher TNF-α level in comparison with the controls (P=0.01). Conclusions. Our results suggest that the measurement of serum IgG4 allows for an identification of patients with more rapid progression of HT, requiring higher doses of L-thyroxine. Low TPOAb level and the absence of coexisting autoimmune diseases may suggest distinct pathomechanism of this type of thyroiditis. PMID:25784936

  10. Neonatal Temperament in Monozygotic and Dizygotic Twin Pairs.

    ERIC Educational Resources Information Center

    Reise, Marilyn L.

    1990-01-01

    Findings indicated that zygosity was not related to behavioral scores during the neonatal period, and that environment substantially influenced neonatal temperament. Specific perinatal indicators of risk were found to account for some of the intrapair differences in behavioral variables. (RH)

  11. Effects of age on H1N1-specific serum IgG1 and IgG3 levels evaluated during the 2011–2012 influenza vaccine season

    PubMed Central

    2013-01-01

    Background We have previously reported an age-related impairment in the serum antibody response to pandemic (p)2009 H1N1, measured by hemagglutination inhibition assay and ELISA. The present study extends these observations and evaluates IgG subclass distribution in healthy individuals of different ages vaccinated during the 2011–2012 season. Results The 2011-2012 vaccination season was characterized by a vaccine containing the pandemic (p)2009 H1N1 strain for the third consecutive year. All of our subjects were previously immunized, and therefore seroprotected at t0. Nevertheless, aging impaired the serum antibody response to H1N1, as antibody titers increased after vaccination in young and less in elderly individuals. The peak of the response was at day 7 (t7), in contrast with what is usually seen at day 21–28, suggesting a memory response characterized by the induction of an IgG subclass with a shorter half-life. We hypothesized that the IgG3 response, with its much shorter half-life, might be more represented. Antibodies were predominantly of the IgG1 subclass in both age groups, although a robust IgG3 response was also induced and accounted for a significant proportion of the overall response. IgG2 and IgG4 antibodies were at indiscernible levels. We showed a much higher percentage of IgG3 (40–50%) than previously in the literature (less than 10%). To explain if this was associated with a particular cytokine profile, we measured H1N1-induced T cell cytokines in vitro and found that IgG3 levels were positively correlated with TNF-α and IL-6. Moreover, activation-induced cytidine deaminase (AID) mRNA expression, a predictive biomarker of optimal in vivo vaccine response, was found to significantly correlate with IgG3 and also with IgG1 similar to what we have shown previously for total IgG. Conclusions In the 2011–2012 season, the pandemic (p)2009 H1N1 strain was present in the vaccine for the third consecutive year and therefore each individual was

  12. Significantly Lower Anti-Leishmania IgG Responses in Sudanese versus Indian Visceral Leishmaniasis

    PubMed Central

    El-Safi, Sayda; Sundar, Shyam; Falconar, Andrew K.; Singh, Om Prakash; Kumar, Rajiv; Ahmed, Osman; Boelaert, Marleen; Miles, Michael A.

    2014-01-01

    Background Visceral leishmaniasis (VL), a widely distributed systemic disease caused by infection with the Leishmania donovani complex (L. donovani and L. infantum), is almost always fatal if symptomatic and untreated. A rapid point-of-care diagnostic test for anti-Leishmania antibodies, the rK39-immunochromatographic test (rK39-ICT), has high sensitivity and specificity in South Asia but is less sensitive in East Africa. One of the underlying reasons may be continent-specific molecular diversity in the rK39 antigen within the L. donovani complex. However, a second reason may be differences in specific IgG anti-Leishmania levels in patients from different geographical regions, either due to variable antigenicity or immunological response. Methodology/Principal Findings We determined IgG titres of Indian and Sudanese VL patients against whole cell lysates of Indian and Sudanese L. donovani strains. Indian VL patients had significantly higher IgG titres against both L. donovani strains compared to Sudanese VL patients (p<0.0001). Mean reciprocal log10 50% end-point titres (1/log10t50) were i) 3.80 and 3.88 for Indian plasma and ii) 2.13 and 2.09 for Sudanese plasma against Indian and Sudanese antigen respectively (p<0.0001). Overall, the Indian VL patients therefore showed a 46.8–61.7 -fold higher mean ELISA titre than the Sudanese VL patients. The higher IgG titres occurred in children (<16 years old) and adults of either sex from India (mean 1/log10t50: 3.60–4.15) versus Sudan (mean 1/log10t50: 1.88–2.54). The greatest difference in IgG responses was between male Indian and Sudanese VL patients of ≥ 16 years old (mean 1/log10t50: 4.15 versus 1.99 = 144-fold (p<0.0001). Conclusions/Significance Anti-Leishmania IgG responses among VL patients in Sudan were significantly lower than in India; this may be due to chronic malnutrition with Zn2+ deficiency, or variable antigenicity and capacity to generate IgG responses to Leishmania antigens. Such differential

  13. Subcutaneous IgG replacement therapy is safe and well tolerated in lung transplant recipients.

    PubMed

    Shankar, T; Gribowicz, J; Crespo, M; Silveira, F P; Pilewski, J; Petrov, A A

    2013-04-01

    Intravenous immunoglobulin (IVIG) replacement has been shown to decrease the risk of post-transplant infections secondary to hypogammaglobulinemia, however the use of subcutaneous immunoglobulin (SCIG) in this population has not been reported. A retrospective analysis of the efficacy and tolerability of subcutaneous immunoglobulin replacement on 10 lung-transplant recipients was performed. All 10 patients demonstrated an increase in IgG levels at three months that was sustained at 6-12 months with SCIG replacement therapy, with the majority (70%) tolerating infusion without complications. The results of this study suggest that subcutaneous IgG replacement therapy is a well tolerated alternative to IVIG. PMID:23499641

  14. Clinical utility of testing AQP4-IgG in CSF

    PubMed Central

    Majed, Masoud; Fryer, James P.; McKeon, Andrew; Lennon, Vanda A.

    2016-01-01

    Objective: To define, using assays of optimized sensitivity and specificity, the most informative specimen type for aquaporin-4 immunoglobulin G (AQP4-IgG) detection. Methods: Results were reviewed from longitudinal service testing for AQP4-IgG among specimens submitted to the Mayo Clinic Neuroimmunology Laboratory from 101,065 individual patients. Paired samples of serum/CSF were tested from 616 patients, using M1-AQP4-transfected cell-based assays (both fixed AQP4-CBA Euroimmun kit [commercial CBA] and live in-house flow cytometry [FACS]). Sensitivities were compared for 58 time-matched paired specimens (drawn ≤30 days apart) from patients with neuromyelitis optica (NMO) or high-risk patients. Results: The frequency of CSF submission as sole initial specimen was 1 in 50 in 2007 and 1 in 5 in 2015. In no case among 616 paired specimens was CSF positive and serum negative. In 58 time-matched paired specimens, AQP4-IgG was detected by FACS or by commercial CBA more sensitively in serum than in CSF (respectively, p = 0.06 and p < 0.001). A serum titer >1:100 predicted CSF positivity (p < 0.001). The probability of CSF positivity was greater around attack time (p = 0.03). No control specimen from 128 neurologic patients was positive by either assay. Conclusions: FACS and commercial CBA detection of AQP4-IgG is less sensitive in CSF than in serum. The data suggest that most AQP4-IgG is produced in peripheral lymphoid tissues and that a critical serum/CSF gradient is required for IgG to penetrate the CNS in pathogenic quantity. Serum is the optimal and most cost-effective specimen for AQP4-IgG testing. Classification of evidence: This study provides Class IV evidence that for patients with NMO or NMOSD, CSF is less sensitive than serum for detection of AQP4-IgG. PMID:27144221

  15. Serial nephelometric urine IgG measurement and the management of pregnancy-induced hypertension.

    PubMed

    Eden, R D; Wahbeh, C J; Williams, A Y; Easley, H A; Gall, S A

    1984-04-15

    Serial IgG analysis was performed on the urine and serum of 16 patients with pregnancy-induced hypertension. Significant immunoglobulinuria developed prior to the development of azotemia, significantly decreased creatinine clearance, significant proteinuria (greater than or equal to 3+ dipstick or greater than or equal to 5 gm per 24-hour urine collection), or oliguria. Nephelometric measurement of urine IgG concentrations appears to be a rapid and accurate method for confirming the severity of clinical disease, the degree of renal involvement, the benefit of treatment modalities on renal function, and the likelihood of postpartum maternal morbidity. PMID:6711642

  16. Neonatal Transfusion Practice: When do Neonates Need Red Blood Cells or Platelets?

    PubMed

    Del Vecchio, Antonio; Franco, Caterina; Petrillo, Flavia; D'Amato, Gabriele

    2016-09-01

    Based on small studies and not on statistically valid clinical trials, guidelines for neonatal transfusions remain controversial and practices vary greatly. Premature infants and critically ill neonates in the neonatal intensive care unit (NICU) often require blood transfusions and extremely preterm neonates receive at least one red blood cell transfusion during their hospital stay. Transfusions to neonates convey both benefits and risks and consequently it is imperative to establish specific guidelines to improve practice and avoid unnecessary transfusions. Appropriate and lifesaving platelet transfusion in thrombocytopenic bleeding neonates pertains to 2% of all neonates in NICUs. Inversely, 98% of platelet transfusions are given prophylactically, in the absence of bleeding, with the assumption that this reduces the risk of a serious hemorrhage. To date, no evidence base is available for assigning a platelet transfusion trigger to NICU patients. Each NICU should approve specific guidelines that best suit its local clinical practice. Therefore, whatever guidelines are chosen in deciding when to transfuse, what is most important is to adhere strictly to the guidelines adopted, thus limiting unnecessary transfusions that convey no benefits and carry both known and unknown risks. PMID:27603540

  17. Neonatal blood rheological parameters at delivery in healthy neonates and in those with morbidities.

    PubMed

    Soliman, Amr A; Csorba, Roland; Tsikouras, Pagnaioti; Wieg, Christian; Harnack, Harald; von Tempelhoff, Georg-Friedrich

    2013-03-26

    Rheological blood parameters of neonates are different form those of adults. Many authors have studied changes in blood rheology in neonates in different clinical disorders. To-date, no one set the normal values for blood rheological parameters in healthy neonates. The aim of this study is to set the norm for rheological blood parameters in healthy newborns and to describe the changes in those parameters in common clinical disorders that affect the newborns. We recruited all the neonates born to mothers experiencing un eventful pregnancies, blood was taken from the umbilical cord right after the delivery. In this time period we recruited 4985 neonate. From this huge database we were able to set the standards for blood rheology in neonates, namely plasma viscosity of 1.06 ± 0.072 mPa, erythrocyte aggregation at stasis of 2.41 ± 2.74 s-1 and erythrocyte aggregation under low shear forces of 8.51 ± 6.38 s-1. These values changed significantly in some diseased neonates. This is the largest study investigating normal rheological parameters and deviations from the norm in common clinical disorders occurring in this early stage of life. PMID:23532177

  18. Ethical issues in neonatal research involving human subjects.

    PubMed

    Fleischman, Alan R

    2016-06-01

    Research involving critically ill neonates creates many ethical challenges. Neonatal clinical research has always been hard to perform, is very expensive, and may generate some unique ethical concerns. This article describes some examples of historical and modern controversies in neonatal research, discusses the justification for research involving such vulnerable and fragile patients, clarifies current federal regulations that govern research involving neonates, and suggests ways that clinical investigators can develop and implement ethically grounded human subjects research. PMID:26804381

  19. Biological markers of neonatal calf performance: the relationship of insulin-like growth factor-I, zinc, and copper to poor neonatal growth.

    PubMed

    Graham, T W; Breher, J E; Farver, T B; Cullor, J S; Kehrli, M E; Oberbauer, A M

    2010-08-01

    Raising a heifer calf to reproductive age represents an enormous cost to the producer. Poor neonatal growth exacerbates the costs incurred for rearing, and use of blood variables that may be associated with poorly growing calves may offer predictive value for growth and performance. Thus, the principal objective of the present study was to describe changes in serum IGF-I, zinc, and copper from birth to 90 d in Holstein calves, while accounting for sex and twin status, in poorly growing calves and calves growing well. A second objective was to test the hypothesis that an association exists between these serum variables and morphometric indicators of growth. Measurements of BW, length, and height were recorded at birth and at 30, 60, and 90 d of age. Jugular blood (12 mL) was collected from each calf on d 1 to determine serum total protein, serum IgG, packed cell volume, serum zinc, serum copper, serum IGF-I, and CD18 genotype for bovine leukocyte adhesion deficiency; serum zinc, serum copper, and serum IGF-I (predictor variables) were also determined for each calf on d 2 through 10 and on d 30, 60, and 90. Stepwise multiple regression and logistic regression analyses were used to examine the relationships between the predictor variables and the dependent variables (BW, height, and length at d 30, 60, and 90 of life). Birth weight, sex, serum IGF-I (at all ages), serum copper, and the serum copper-to-zinc ratio were associated, to varying degrees, with the dependent growth variables. Birth weight was consistently the dominant predictor. In conclusion, these results suggest that lighter birth weight, reduced serum IGF-I, and inflammation may be important causes of poor growth in neonatal Holstein dairy calves. PMID:20382870

  20. Fusion of the mouse IgG1 Fc domain to the VHH fragment (ARP1) enhances protection in a mouse model of rotavirus

    PubMed Central

    Günaydın, Gökçe; Yu, Shengze; Gräslund, Torbjörn; Hammarström, Lennart; Marcotte, Harold

    2016-01-01

    A variable fragment of a heavy chain antibody (VHH) directed against rotavirus, also referred to as anti-rotavirus protein 1 (ARP1), was shown to confer protection against rotavirus induced diarrhea in infant mouse model of rotavirus induced diarrhea. In this study, we have fused the mouse IgG1 Fc to ARP1 to improve the protective capacity of ARP1 by inducing an Fc-mediated effector function. We have shown that the Fc-ARP1 fusion protein confers significantly increased protection against rotavirus in a neonatal mouse model of rotavirus-induced diarrhea by reducing the prevalence, duration and severity of diarrhea and the viral load in the small intestines, suggesting that the Fc part of immunoglobulins may be engaged in Fc-mediated neutralization of rotavirus. Engineered conventional-like antibodies, by fusion of the Fc part of immunoglobulins to antigen-specific heavy-chain only VHH fragments, might be applied to novel antibody-based therapeutic approaches to enhance elimination of pathogens by activation of distinct effector signaling pathways. PMID:27439689

  1. Fusion of the mouse IgG1 Fc domain to the VHH fragment (ARP1) enhances protection in a mouse model of rotavirus.

    PubMed

    Günaydın, Gökçe; Yu, Shengze; Gräslund, Torbjörn; Hammarström, Lennart; Marcotte, Harold

    2016-01-01

    A variable fragment of a heavy chain antibody (VHH) directed against rotavirus, also referred to as anti-rotavirus protein 1 (ARP1), was shown to confer protection against rotavirus induced diarrhea in infant mouse model of rotavirus induced diarrhea. In this study, we have fused the mouse IgG1 Fc to ARP1 to improve the protective capacity of ARP1 by inducing an Fc-mediated effector function. We have shown that the Fc-ARP1 fusion protein confers significantly increased protection against rotavirus in a neonatal mouse model of rotavirus-induced diarrhea by reducing the prevalence, duration and severity of diarrhea and the viral load in the small intestines, suggesting that the Fc part of immunoglobulins may be engaged in Fc-mediated neutralization of rotavirus. Engineered conventional-like antibodies, by fusion of the Fc part of immunoglobulins to antigen-specific heavy-chain only VHH fragments, might be applied to novel antibody-based therapeutic approaches to enhance elimination of pathogens by activation of distinct effector signaling pathways. PMID:27439689

  2. Human Antibodies Can Cross Guinea Pig Placenta and Bind Its Neonatal Fc Receptor: Implications for Studying Immune Prophylaxis and Therapy during Pregnancy

    PubMed Central

    Struble, Evi Budo; Ma, Li; Zhong, Lilin; Lesher, A.; Beren, Joel; Zhang, Pei

    2012-01-01

    Despite increased use of monoclonal and polyclonal antibody therapies, including during pregnancy, there is little data on appropriate animal models that could humanely be used to understand determinants of protection and to evaluate safety of these biologics in the mother and the developing fetus. Here, we demonstrate that pregnant guinea pigs can transport human IgG transplacentally at the end of pregnancy. We also observe that human IgG binds to an engineered soluble variant of the guinea pig neonatal Fc receptor in vitro in a manner similar to that demonstrated for the human variant, suggesting that this transplacental transport mirrors the receptor-based mechanism seen in humans. Using an intravenous antihepatitis B-specific immune globulin preparation as an example, we show that this transport results in neutralizing activity in the mother and the newborn that would potentially be prophylactic against hepatitis B viral infection. These preliminary data lay the groundwork for introducing pregnant guinea pigs as an appropriate model for the evaluation of antibody therapies and advancing the health of women and neonates. PMID:22991567

  3. Human antibodies can cross guinea pig placenta and bind its neonatal Fc Receptor: implications for studying immune prophylaxis and therapy during pregnancy.

    PubMed

    Struble, Evi Budo; Ma, Li; Zhong, Lilin; Lesher, A; Beren, Joel; Zhang, Pei

    2012-01-01

    Despite increased use of monoclonal and polyclonal antibody therapies, including during pregnancy, there is little data on appropriate animal models that could humanely be used to understand determinants of protection and to evaluate safety of these biologics in the mother and the developing fetus. Here, we demonstrate that pregnant guinea pigs can transport human IgG transplacentally at the end of pregnancy. We also observe that human IgG binds to an engineered soluble variant of the guinea pig neonatal Fc receptor in vitro in a manner similar to that demonstrated for the human variant, suggesting that this transplacental transport mirrors the receptor-based mechanism seen in humans. Using an intravenous antihepatitis B-specific immune globulin preparation as an example, we show that this transport results in neutralizing activity in the mother and the newborn that would potentially be prophylactic against hepatitis B viral infection. These preliminary data lay the groundwork for introducing pregnant guinea pigs as an appropriate model for the evaluation of antibody therapies and advancing the health of women and neonates. PMID:22991567

  4. Antibodies to capsular polysaccharides of group B Streptococcus in pregnant Canadian women: relationship to colonization status and infection in the neonate.

    PubMed

    Davies, H D; Adair, C; McGeer, A; Ma, D; Robertson, S; Mucenski, M; Kowalsky, L; Tyrell, G; Baker, C J

    2001-08-01

    In a cohort study of 1207 pregnant women in Alberta, Canada, the serotype distributions of vaginal-rectal group B Streptococcus (GBS) isolates were compared with all isolates from neonates with invasive GBS disease identified by population-based surveillance. Serum concentrations of Ia, Ib, II, III, and V capsular polysaccharide (CPS)-specific IgG also were determined, according to serotype of the vaginal-rectal colonizing GBS strain. GBS colonization was detected in 19.5% (235 of 1207) of women. Serotype III accounted for 20.6% (48 of 233) of colonizing strains available for typing but for 37% (27 of 73) of invasive isolates from neonates (P<.01). Maternal colonization with type III was least likely to be associated with moderate concentrations of III CPS-specific IgG. Serotype III GBS is more invasive than other serotypes in this population; this may be due, at least in part, to poor maternal type III CPS-specific antibody response. PMID:11443553

  5. Refractory Bacillus cereus infection in a neonate.

    PubMed

    Tuladhar, R; Patole, S K; Koh, T H; Norton, R; Whitehall, J S

    2000-06-01

    Bacillus cereus is a Gram-positive aerobic or facultatively anaerobic spore-forming rod, which usually causes food poisoning. Its recognition as a pathogen in neonates has increased over the past two decades. The clinical course of a neonate (gestation 24 weeks) with B. cereus infection refractory to therapy is described. Death occurred after withdrawal of support following persistently positive blood and bone marrow cultures despite therapy with vancomycin, gentamicin, imipenum, clindamycin, ciprofloxacillin, immunoglobulin and granulocyte colony stimulating factor over a period of 49 days. No obvious focus of sepsis was identified. Contamination from the environment into the hospital and clinics occurs because of the ubiquitous presence of B. cereus. Combination therapy with vancomycin and gentamycin is appropriate for meningitis/severe systemic infections related to most bacillus species. The significance of repeated isolation of B. cereus in neonates with compromised host defences is emphasised. PMID:10954966

  6. Behavioral assessment of a hydranencephalic neonate.

    PubMed

    Francis, P L; Self, P A; McCaffree, M A

    1984-02-01

    This study attempted to clarify the role of the cerebral cortex in neonatal behavior by administering the Neonatal Behavioral Assessment Scale-Kansas revision to a hydranencephalic infant; particularly of interest were behaviors that are implicated in infant social responsiveness. The examination revealed extremely deviant responses on portions of the exam, including items that measure response decrement and orientation. However, this infant was observed to approximate normal neonatal responding on items relating to motor maturity and reactivity. Other findings included that some response decrement occurred in response to auditory and visual, but not tactile, stimulation. The discussion focuses on similarities and differences between this study and early research on both normal infants and infants with imperfectly formed nervous systems. Particular emphasis is placed on the response decrement results, as well as the utility of the NBAS-K in measuring infant behaviors in atypical infant samples. PMID:6705627

  7. Cryopreservation of ovaries from neonatal marmoset monkeys.

    PubMed

    Motohashi, Hideyuki H; Ishibashi, Hidetoshi

    2016-07-29

    The ovary of neonatal nonhuman primates contains the highest number of immature oocytes, but its cryopreservation has not yet been sufficiently investigated in all life stages. In the current study, we investigated cryodamage after vitrification/warming of neonatal ovaries from a nonhuman primate, the common marmoset (Callithrix jacchus). A Cryotop was used for cryopreservation of whole ovaries. The morphology of the vitrified/warmed ovaries was found to be equivalent to that of fresh ovaries. No significant difference in the number of oocytes retaining normal morphology per unit area in histological sections was found between the two groups. In an analysis of dispersed cells from the ovaries, however, the cell viability of the vitrified/warmed group tended to be decreased. The results of a comet assay showed no significant differences in DNA damage. These results show that cryopreservation of neonatal marmoset ovaries using vitrification may be useful as a storage system for whole ovaries. PMID:26876597

  8. [Neonatal hyperthyroidism and maternal Graves disease].

    PubMed

    Ben Ameur, K; Chioukh, F Z; Marmouch, H; Ben Hamida, H; Bizid, M; Monastiri, K

    2015-04-01

    The onset of Graves disease during pregnancy exposes the neonate to the risk of hyperthyroidism. The newborn must be monitored and treatment modalities known to ensure early treatment of the newborn. We report on the case of an infant born at term of a mother with Graves disease discovered during pregnancy. He was asymptomatic during the first days of life, before declaring the disease. Neonatal hyperthyroidism was confirmed by hormonal assays. Hyperthyroidism was treated with antithyroid drugs and propranolol with a satisfactory clinical and biological course. Neonatal hyperthyroidism should be systematically sought in infants born to a mother with Graves disease. The absence of clinical signs during the first days of life does not exclude the diagnosis. The duration of monitoring should be decided according to the results of the first hormonal balance tests. PMID:25727474

  9. Pulmonary surfactant for neonatal respiratory disorders.

    PubMed

    Merrill, Jeffrey D; Ballard, Roberta A

    2003-04-01

    Surfactant therapy has revolutionized neonatal care and is used routinely for preterm infants with respiratory distress syndrome. Recent investigation has further elucidated the function of surfactant-associated proteins and their contribution toward surfactant and lung immune defense functions. As the field of neonatology moves away from intubation and mechanical ventilation of preterm infants at birth toward more aggressive use of nasal continuous positive airway pressure, the optimal timing of exogenous surfactant therapy remains unclear. Evidence suggests that preterm neonates with bronchopulmonary dysplasia and prolonged mechanical ventilation also experience surfactant dysfunction; however, exogenous surfactant therapy beyond the first week of life has not been well studied. Surfactant replacement therapy has been studied for use in other respiratory disorders, including meconium aspiration syndrome and pneumonia. Commercial surfactant preparations currently available are not optimal, given the variability of surfactant protein content and their susceptibility to inhibition. Further progress in the treatment of neonatal respiratory disorders may include the development of "designer" surfactant preparations. PMID:12640270

  10. Cryopreservation of ovaries from neonatal marmoset monkeys

    PubMed Central

    Motohashi, Hideyuki H.; Ishibashi, Hidetoshi

    2016-01-01

    The ovary of neonatal nonhuman primates contains the highest number of immature oocytes, but its cryopreservation has not yet been sufficiently investigated in all life stages. In the current study, we investigated cryodamage after vitrification/warming of neonatal ovaries from a nonhuman primate, the common marmoset (Callithrix jacchus). A Cryotop was used for cryopreservation of whole ovaries. The morphology of the vitrified/warmed ovaries was found to be equivalent to that of fresh ovaries. No significant difference in the number of oocytes retaining normal morphology per unit area in histological sections was found between the two groups. In an analysis of dispersed cells from the ovaries, however, the cell viability of the vitrified/warmed group tended to be decreased. The results of a comet assay showed no significant differences in DNA damage. These results show that cryopreservation of neonatal marmoset ovaries using vitrification may be useful as a storage system for whole ovaries. PMID:26876597

  11. Neonatal Abstinence Syndrome: Presentation and Treatment Considerations.

    PubMed

    Jones, Hendrée E; Kaltenbach, Karol; Johnson, Elisabeth; Seashore, Carl; Freeman, Emily; Malloy, Erin

    2016-01-01

    This clinical case conference discusses the treatment of a pregnant woman with opioid use disorder in a comprehensive care program that includes buprenorphine pharmacotherapy. The presentation summarizes common experiences that pregnant women who receive buprenorphine pharmacotherapy face, and also what their prenatally opioid-exposed children confront in the immediate postpartum period. It describes the elements of a successful comprehensive care model and corollary neonatal abstinence syndrome treatment regimen. Expert commentary is included on issues that arise in the buprenorphine induction and maintenance throughout the prenatal and postpartum periods and in the treatment of co-occurring mental health problems during both the prenatal and postpartum periods, particularly the treatment of depression. There is also expert commentary on the care of opioid-exposed neonates, with attention to the treatment for neonatal abstinence syndrome. PMID:27244045

  12. Neonatal management of pregnancy complicated by diabetes.

    PubMed

    Mohsin, Fauzia; Khan, Shareen; Baki, Md Abdul; Zabeen, Bedowra; Azad, Kiswhar

    2016-09-01

    Women with diabetes in pregnancy, either pre-gestational Diabetes Mellitus (Type 1 & Type 2) or Gestational Diabetes, are at increased risk for adverse pregnancy outcomes, including preterm labour and increased foetal mortality rate. Adequate glycaemic control before and during pregnancy is crucial for improving foetal and perinatal outcomes in these babies. Perinatal and neonatal morbidities and mortality rates have declined since the development of specialized maternal, foetal, and neonatal care for women with diabetes and their offspring. However, infants of diabetic mothers are at risk for developing complications as macrosomia, hypoglycaemia, perinatal asphyxia, cardiac and respiratory problems, birth injuries and congenital malformations. In this review article we describe the neonatal management of the offspring of diabetic mothers. PMID:27582162

  13. The neonatal nurse: advocating for breastfeeding mothers.

    PubMed

    Darby, Colm; Nurse, Sharon

    2016-02-01

    Accurate information and support from healthcare professionals as well as respect for parental choice are all factors which contribute to effective breastfeeding in the neonatal unit; with this in mind, Colm Darby and Sharon Nurse discuss the potential problems in expressing breast milk and the interventions which might be effective in avoiding them. Advocacy is an inherent part of neonatal nurses' role whilst caring for sick, vulnerable babies. Colm Darby is a male neonatal nurse working in a predominantly female environment and passionately believes in supporting and advocating for mothers who want to provide breast milk for their babies. In this article, CoIm uses Borton's model of reflection to discuss how he acted as an effective advocate for such a mother. PMID:27008754

  14. 21 CFR 880.5270 - Neonatal eye pad.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Neonatal eye pad. 880.5270 Section 880.5270 Food... § 880.5270 Neonatal eye pad. (a) Identification. A neonatal eye pad is an opaque device used to cover and protect the eye of an infant during therapeutic procedures, such as phototherapy....

  15. 21 CFR 880.5270 - Neonatal eye pad.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Neonatal eye pad. 880.5270 Section 880.5270 Food... § 880.5270 Neonatal eye pad. (a) Identification. A neonatal eye pad is an opaque device used to cover and protect the eye of an infant during therapeutic procedures, such as phototherapy....

  16. 21 CFR 880.5270 - Neonatal eye pad.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Neonatal eye pad. 880.5270 Section 880.5270 Food... § 880.5270 Neonatal eye pad. (a) Identification. A neonatal eye pad is an opaque device used to cover and protect the eye of an infant during therapeutic procedures, such as phototherapy....

  17. 21 CFR 880.5270 - Neonatal eye pad.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Neonatal eye pad. 880.5270 Section 880.5270 Food... § 880.5270 Neonatal eye pad. (a) Identification. A neonatal eye pad is an opaque device used to cover and protect the eye of an infant during therapeutic procedures, such as phototherapy....

  18. 21 CFR 880.5270 - Neonatal eye pad.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Neonatal eye pad. 880.5270 Section 880.5270 Food... § 880.5270 Neonatal eye pad. (a) Identification. A neonatal eye pad is an opaque device used to cover and protect the eye of an infant during therapeutic procedures, such as phototherapy....

  19. Status of Neonatal Pain Assessment and Management in Jordan.

    PubMed

    Abdel Razeq, Nadin M; Akuma, Akuma O; Jordan, Sue

    2016-08-01

    Current pain assessment and management in neonates need to be fully described before neonatal pain care can be optimized. This study's purpose was to report neonatal nurses' knowledge, existing pain assessment practice, and pharmacological pain management of neonates in Jordan. A cross-sectional descriptive study was conducted. Eighteen neonatal intensive care units in Jordan were included in the study. One hundred eighty-four neonatal nurses participated. Questionnaires were distributed by and returned to the neonatal intensive care units' managers between June and August 2014. Descriptive and inferential statistics were used to present study results. Of 240 questionnaires distributed, 184 useable responses were returned. Nurses' knowledge regarding neonates' neurological development, nociception, and need for neonatal pain management was suboptimal. The analgesics most commonly used to treat neonatal pain were acetaminophen (52%) and lidocaine (45%). Benzodiazepines, phenobarbitone, and muscles relaxants were also used. Most nurses (54%-97%) reported that pain emanating from most painful procedures was never or rarely treated. Circumcision, lumbar punctures, and chest tube insertion were assigned the highest pain scores (≥9), but were rarely accompanied by analgesia. Pain assessment scales were more likely to be used, and procedural pain was more likely to be treated, in private hospitals than public hospitals. Neonates who require special care still suffer unnecessary pain that could be avoided and managed by following best practice recommendations. Disparities between developed and developing countries in quality of neonatal pain care appear to exist. Resources for education and routine care are needed to address these discrepancies. PMID:27108085

  20. 21 CFR 880.5410 - Neonatal transport incubator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Neonatal transport incubator. 880.5410 Section 880... Devices § 880.5410 Neonatal transport incubator. (a) Identification. A neonatal transport incubator is a... kept in a controlled environment while being transported for medical care. The device may...