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Sample records for anticuerpos igm antivirus

  1. Crispen's Five Antivirus Rules.

    ERIC Educational Resources Information Center

    Crispen, Patrick Douglas

    2000-01-01

    Explains five rules to protect computers from viruses. Highlights include commercial antivirus software programs and the need to upgrade them periodically (every year to 18 months); updating virus definitions at least weekly; scanning attached files from email with antivirus software before opening them; Microsoft Word macro protection; and the

  2. Crispen's Five Antivirus Rules.

    ERIC Educational Resources Information Center

    Crispen, Patrick Douglas

    2000-01-01

    Provides rules for protecting computers from viruses, Trojan horses, or worms. Topics include purchasing commercial antivirus programs and keeping them updated; updating virus definitions weekly; precautions before opening attached files; macro virus protection in Microsoft Word; and precautions with executable files. (LRW)

  3. [IgM myeloma].

    PubMed

    Roujeau, J C; Bisson, M; Segond, P; Massias, P

    1976-11-23

    The authors report the case of a 62 year old woman in whom bony pain led to the discovery of lacunar osteolytic appearances, in particular in the skull, abnormal medullary plasmacytosis and serum monoclonal immunoglobulin with Bence-Jones proteinuria. The case was unusual as the immunoglobulin observed was an IgM. This finding led the authors to a critical revision of the distinctive characteristics of multiple myeloma and Waldenstrm's macro-globulinemia, emphasizing the distinguishing value of the cytological criterion. The authors recall the various neoplastic proliferations of the B lymphocytes at the various stages of their maturation and emphasize the predominance of monoclonal IgM during proliferations affecting the early stages of maturation of the B lymphocytes and the rareness of these IgM during plasma cell neoplasms. PMID:188179

  4. Impact of anti-virus software on computer virus dynamical behavior

    NASA Astrophysics Data System (ADS)

    Sun, Mei; Li, Dandan; Han, Dun; Jia, Changsheng

    2014-11-01

    The impact of anti-virus software on the spreading of computer virus is investigated via developing a mathematical model in this paper. Considering the anti-virus software may not be effective, as it may be an outdated version, and then the computers may be infected with a reduced incidence rate. According to the method of next generation matrix, the basic reproduction number is derived. By introducing appropriate Lyapunov function and the Routh stability criterion, acquiring the stability conditions of the virus-free equilibrium and virus equilibrium. The effect of anti-virus software and disconnecting rate on the spreading of virus are also analyzed. When combined with the numerical results, a set of suggestions are put forward for eradicating virus effectively.

  5. Effect of anti-virus software on infectious nodes in computer network: A mathematical model

    NASA Astrophysics Data System (ADS)

    Mishra, Bimal Kumar; Pandey, Samir Kumar

    2012-07-01

    An e-epidemic model of malicious codes in the computer network through vertical transmission is formulated. We have observed that if the basic reproduction number is less than unity, the infected proportion of computer nodes disappear and malicious codes die out and also the malicious codes-free equilibrium is globally asymptotically stable which leads to its eradication. Effect of anti-virus software on the removal of the malicious codes from the computer network is critically analyzed. Analysis and simulation results show some managerial insights that are helpful for the practice of anti-virus in information sharing networks.

  6. Coping with Computer Viruses: General Discussion and Review of Symantec Anti-Virus for the Macintosh.

    ERIC Educational Resources Information Center

    Primich, Tracy

    1992-01-01

    Discusses computer viruses that attack the Macintosh and describes Symantec AntiVirus for Macintosh (SAM), a commercial program designed to detect and eliminate viruses; sample screen displays are included. SAM is recommended for use in library settings as well as two public domain virus protection programs. (four references) (MES)

  7. Theoretical and experimental analysis of the impacts of removable storage media and antivirus software on viral spread

    NASA Astrophysics Data System (ADS)

    Gan, Chenquan; Yang, Xiaofan

    2015-05-01

    In this paper, a new computer virus propagation model, which incorporates the effects of removable storage media and antivirus software, is proposed and analyzed. The global stability of the unique equilibrium of the model is independent of system parameters. Numerical simulations not only verify this result, but also illustrate the influences of removable storage media and antivirus software on viral spread. On this basis, some applicable measures for suppressing virus prevalence are suggested.

  8. Nucleotide bias of DCL and AGO in plant anti-virus gene silencing.

    PubMed

    Ho, Thien; Wang, Liang; Huang, Linfeng; Li, Zhigang; Pallett, Denise W; Dalmay, Tamas; Ohshima, Kazusato; Walsh, John A; Wang, Hui

    2010-09-01

    Plant Dicer-like (DCL) and Argonaute (AGO) are the key enzymes involved in anti-virus post-transcriptional gene silencing (AV-PTGS). Here we show that AV-PTGS exhibited nucleotide preference by calculating a relative AV-PTGS efficiency on processing viral RNA substrates. In comparison with genome sequences of dicot-infecting Turnip mosaic virus (TuMV) and monocot-infecting Cocksfoot streak virus (CSV), viral-derived small interfering RNAs (vsiRNAs) displayed positive correlations between AV-PTGS efficiency and G+C content (GC%). Further investigations on nucleotide contents revealed that the vsiRNA populations had G-biases. This finding was further supported by our analyses of previously reported vsiRNA populations in diverse plant-virus associations, and AGO associated Arabidopsis endogenous siRNA populations, indicating that plant AGOs operated with G-preference. We further propose a hypothesis that AV-PTGS imposes selection pressure(s) on the evolution of plant viruses. This hypothesis was supported when potyvirus genomes were analysed for evidence of GC elimination, suggesting that plant virus evolution to have low GC% genomes would have a unique function, which is to reduce the host AV-PTGS attack during infections. PMID:21203927

  9. IgM nephropathy; time to act.

    PubMed

    Mubarak, Muhammed

    2014-01-01

    Implication for health policy/practice/research/medical education: Much has been published on the epidemiology and clinicopathological characteristics of IgM nephropathy, but there is little information on the etiology,pathogenesis and specific therapy of the disease. Controversy still shrouds the definition and nosologic status of the disease. Well-coordinated and concerted international efforts and collaboration between researchers in the developing and developed countries are needed to make further progress on the above aspects of the disease. PMID:24644539

  10. IgM in the kidney: a multiple personality disorder.

    PubMed

    Platt, Jeffrey L; Cascalho, Marilia

    2015-09-01

    IgM in the blood of normal individuals consists mainly of 'natural' polyreactive antibodies. Natural IgM is thought to provide an initial defense against infection and to promote the healing of wounded cells. Yet, as Panzer and colleagues show, these benefits can be eclipsed when the IgM binds to damaged cells of the glomerulus, activating complement. IgM in glomeruli thus signifies cellular damage and may warn that the pace of that damage exceeds the capacity for repair. PMID:26323070

  11. Intrafamilial correlation analysis for IgM serum levels.

    PubMed Central

    Guzar-Vzquez, J; Saint-Martin, F P; Rostenberg, I; Surez, P E; Armendares, S

    1977-01-01

    The IgM serum level was determined in the members of 29 healthy families. The IgM mean concentrations between fathers and mothers and between sons and daughters were significantly different (P less than .01), with higher serum IgM levels in females than in males. Simple linear regression analysis was done for the following intrafamilial combinations: son-father, daughter-father, son-mother, and daughter-mother. Significant correlation coefficients (P less than .05) were obtained in all four combinations, which does not support the X-linked gene hypothesis (i.e., that the X chromosome carries quantitative genes for immunoglobulin M). An alternative explanation for the differences between sexes for IgM serum concentration is considered. PMID:930923

  12. Protective Roles of Natural IgM Antibodies

    PubMed Central

    Grnwall, Caroline; Vas, Jaya; Silverman, Gregg J.

    2012-01-01

    Antibodies are a vital part of the armamentarium of the adaptive immune system for the fine-tuning of the recognition and response to foreign threats. However, in health there are some types of antibodies that instead recognize self-antigens and these contribute to the enhancement of primitive innate functions. This repertoire of natural IgM antibodies is postulated to have been selected during immune evolution for their contributions to critical immunoregulatory and housekeeping properties. The clearance of dying cells is one of the most essential responsibilities of the immune system, which is required to prevent uncontrolled inflammation and autoimmunity. In the murine immune system, natural IgM antibodies that recognize apoptotic cells have been shown to enhance the phagocytic clearance of dead and dying cells and to suppress innate immune signaling pathways. In the mouse, natural IgM are often the products of B-1 cell clones that arise during immune development without an absolute requirement for exogenous antigenic stimulation. In patients with systemic lupus erythematosus, IgM autoantibodies, which bind to neo-epitopes on apoptotic cells, have been demonstrated to be present at significantly higher levels in patients with lower disease activity and with less severe organ damage. While certain specificities of IgM autoantibodies correlate with protection from lupus renal disease, others may convey protective properties from lupus-associated atherosclerotic cardiovascular disease. New and unexpected insights into the functional roles of IgM antibodies are still emerging, especially regarding the functions of natural antibodies. Herein, we review recent progress in our understanding of the potential roles of natural IgM autoantibodies in the regulation of immune homeostasis and for protection from autoimmune and inflammatory diseases. PMID:22566947

  13. Evaluation of the IMMULITE 2000 CMV IgM assay

    PubMed Central

    2012-01-01

    Background Diagnosis of cytomegalovirus (CMV) infection is challenging because of the high rate of asymptomatic infection and the low specificity of associated symptoms and signs. As a result, laboratory testing is an essential aid in making an accurate diagnosis. The presence of CMV IgM is indicative of primary CMV infection. In pregnancy, diagnosis of primary infection is important because primary maternal infection increases fetal infection risk substantially. Fetal infection can result in serious sequelae ranging from neurological deficits to death. Diagnosis among the immunocompromised is also critical for the timely initiation of therapy that can reduce morbidity and mortality risk. Methods The IMMULITE 2000 CMV IgM assay qualitatively detects CMV IgM antibodies in human serum or plasma to aid in the diagnosis of current or recent CMV infection. To determine expected values in apparently healthy subjects, 136 samples were tested. Reproducibility, normal range, and method comparison studies were also performed to evaluate the assay's performance. The assay's reproducibility was evaluated across three sites. Seven hundred and eighteen (n = 718) individual patient serum samples, which included samples from CMV IgM-positive (n = 109, determined by the Abbott IMx CMV or the Diamedix CMV IgM assays), pregnant (n = 210), HIV-positive (n = 30), immunosuppressed (n = 102), and transplant patients (n = 17) and from patients with potentially cross-reacting conditions (n = 136) were evaluated in the method comparison study. The positive, negative, and overall agreement between the IMMULITE 2000 CMV IgM assay and the VIDAS CMV IgM assay (predicate assay) were determined. Results The assay demonstrated excellent reproducibility with a total CV of less than 10%. The positive, negative, and overall agreement between the IMMULITE 2000 assay and the VIDAS assay were > 95% for the method comparison samples. Among potentially cross-reactive samples, the overall agreement between the two assays was 96%. Similarly, among the immunocompromised and pregnant subjects, the overall agreement was ~96% and ~97%, respectively. Conclusions The IMMULITE 2000 CMV IgM assay demonstrated excellent reproducibility, minimal cross-reactivity, and performance comparable to that of the VIDAS CMV IgM assay. It can aid in the diagnosis of acute CMV or recent CMV infection by qualitatively detecting the CMV IgM antibodies in human serum or plasma. PMID:22377002

  14. IgM rheumatoid factor removal and performance of the FTA-ABS (IgM) test in congenital syphilis.

    PubMed Central

    Meyer, M P; Roditi, D; Louw, S

    1992-01-01

    OBJECTIVE--To determine the performance of the FTA-ABS (IgM) test in congenital syphilis after eliminating interference by IgM rheumatoid factor (RF) and preventing competitive inhibition by IgG. DESIGN--The FTA-ABS (IgM) test was carried out before and after RF removal (achieved by immunoprecipitation of the IgG) in infants with congenital syphilis and controls. SETTING--Newborns delivered in the Peninsula Maternal and Neonatal Services in Cape Town and infants presenting at Red Cross War Memorial Children's Hospital. SUBJECTS--Infants with congenital syphilis aged 0-4 months were divided into those with clinical signs at presentation and those who were asymptomatic at delivery. In addition, patients without congenital syphilis but with similar clinical signs at presentation were investigated as were control infants. OUTCOME MEASURE--The diagnosis of congenital syphilis was based on the criteria suggested by Kaufman et al (1977). RESULTS--Amongst symptomatic infants with congenital syphilis the FTA-ABS (IgM) test was positive in 34 (92%) of 37 cases prior to abolishing the RF effect and in 29 (78.4%) of 37 cases afterwards (p = 0.19). In 12 cases of congenital syphilis who were asymptomatic at birth, 10 had positive FTA-ABS (IgM) tests before RF removal and only three had positive tests afterwards (p = 0.006). False positive tests were not found amongst 15 symptomatic infants whose clinical features mimicked those of the infants with congenital syphilis. Among 51 healthy infants the test had a false-positive rate of 2% in newborns and 13% in older infants. The false positive reactions were eradicated by IgG precipitation. CONCLUSIONS--Following IgG and RF removal there was an improvement in the specificity of the FTA-ABS (IgM) test but this was at the expense of a loss of sensitivity, particularly in asymptomatic newborns. For newborns, if the FTA-ABS (IgM) test was positive, the patient was likely to require treatment for congenital syphilis, regardless of whether the result was due to the presence of RF or specific IgM. PMID:1398661

  15. Impact of Natural IgM Concentration on Gene Therapy with Adenovirus Type 5 Vectors

    PubMed Central

    Qiu, Qi; Xu, Zhili; Tian, Jie; Moitra, Rituparna; Gunti, Sreenivasulu; Notkins, Abner L.

    2014-01-01

    Natural IgM inhibits gene transfer by adenovirus type 5 (Ad5) vectors. We show that polyreactive natural IgM antibodies bind to Ad5 and that inhibition of liver transduction by IgM depends on Kupffer cells. By manipulating IgM concentration in vivo, we demonstrate that IgM inhibits liver transduction in a concentration-dependent manner. We further show that differences in natural IgM between BALB/c and C57BL/6 mice contribute to lower efficiency of Ad5 gene transfer in BALB/c mice. PMID:25552715

  16. Multiple recurrent hordeola associated with selective IgM deficiency.

    PubMed

    Kiratli, H K; Akar, Y

    2001-02-01

    An external hordeolum is an acute, suppurative inflammation of the glands of Zeis and sweat glands or hair follicles most commonly caused by staphylococci, usually in the setting of a chronic blepharitis.(1) We report a case of a boy with unilateral multiple recurrent hordeola in association with selective IgM deficiency. PMID:11182678

  17. [Rapid detection of Mycoplasma pneumoniae-specific IgM].

    PubMed

    Iwasawa, A; Nakamura, Y

    1999-12-01

    The rapid diagnosis of Mycoplasma pneumoniae infection is important in carrying out chemotherapy in appropriate manner. It is also essential to detect the specific immunoglobulin M (IgM) in order to diagnose infectious diseases. The ImmunoCard Mycoplasma kit (TFB. Inc./Meridian Diagnostics, Inc.) is a 10-min-card-based enzyme-linked immunosorbent assay (ELISA) of IgM antibodies to M. pneumoniae. The ImmunoCard was compared with high density particle agglutination (HDPA) and cold hemagglutinin (CHA). The ImmunoCard test had 98.3% sensitivity, 51.4% specificity, and 72.5% agreement with HDPA (>or =320), but it had 94.3% sensitivity, 87.5% specificity, and 92.2% agreement with clinical diagnosis. Our results indicate that the ImmunoCard Mycoplasma IgM assay is a rapid, simple and valuable procedure which can be analyze small numbers of specimens using a less complicated technique and with no other equipment required. This means that the ImmunoCard is a cost-effective, energy saving and rapid procedure for the detection of M. pneumoniae-specific IgM. PMID:10681711

  18. A Reassessment of IgM Memory Subsets in Humans.

    PubMed

    Bagnara, Davide; Squillario, Margherita; Kipling, David; Mora, Thierry; Walczak, Aleksandra M; Da Silva, Lucie; Weller, Sandra; Dunn-Walters, Deborah K; Weill, Jean-Claude; Reynaud, Claude-Agnès

    2015-10-15

    From paired blood and spleen samples from three adult donors, we performed high-throughput VH sequencing of human B cell subsets defined by IgD and CD27 expression: IgD(+)CD27(+) ("marginal zone [MZ]"), IgD(-)CD27(+) ("memory," including IgM ["IgM-only"], IgG and IgA) and IgD(-)CD27(-) cells ("double-negative," including IgM, IgG, and IgA). A total of 91,294 unique sequences clustered in 42,670 clones, revealing major clonal expansions in each of these subsets. Among these clones, we further analyzed those shared sequences from different subsets or tissues for VH gene mutation, H-CDR3-length, and VH/JH usage, comparing these different characteristics with all sequences from their subset of origin for which these parameters constitute a distinct signature. The IgM-only repertoire profile differed notably from that of MZ B cells by a higher mutation frequency and lower VH4 and higher JH6 gene usage. Strikingly, IgM sequences from clones shared between the MZ and the memory IgG/IgA compartments showed a mutation and repertoire profile of IgM-only and not of MZ B cells. Similarly, all IgM clonal relationships (among MZ, IgM-only, and double-negative compartments) involved sequences with the characteristics of IgM-only B cells. Finally, clonal relationships between tissues suggested distinct recirculation characteristics between MZ and switched B cells. The "IgM-only" subset (including cells with its repertoire signature but higher IgD or lower CD27 expression levels) thus appear as the only subset showing precursor-product relationships with CD27(+) switched memory B cells, indicating that they represent germinal center-derived IgM memory B cells and that IgM memory and MZ B cells constitute two distinct entities. PMID:26355154

  19. Genetics Home Reference: X-linked hyper IgM syndrome

    MedlinePLUS

    ... PubMed Recent literature OMIM Genetic disorder catalog Conditions > X-linked hyper IgM syndrome On this page: Description ... names Glossary definitions Reviewed April 2013 What is X-linked hyper IgM syndrome? X-linked hyper IgM ...

  20. Sequence analyses of three immunoglobulin G anti-virus antibodies reveal their utilization of autoantibody-related immunoglobulin Vh genes, but not V lambda genes.

    PubMed

    Huang, D F; Olee, T; Masuho, Y; Matsumoto, Y; Carson, D A; Chen, P P

    1992-12-01

    Accumulated sequence analyses of the antibody repertoire have revealed that most autoantibodies and developmentally regulated antibodies share a small set of germline Ig-variable region (V) genes. The findings have prompted speculation that certain autoantibodies are of developmental importance and may be instrumental in maintaining homeostasis of the adult antibody repertoire. In order to evaluate this hypothesis critically, it is first necessary to determine the V gene usage in human antibodies against foreign substances. Unfortunately, only a few such antibodies have had their heavy and light chains characterized. To rectify the situation, we adapted the anchored polymerase chain reaction to clone and analyze rapidly the expressed V genes for three anti-virus IgG antibodies. The results show that all three heavy chain V (Vh) genes are highly homologous to the known autoantibody-related Vh genes. In contrast, two light chain V (VL) genes of the V lambda 1 subgroup are similar to a non-autoantibody-related germline V lambda 1 gene. Taken together with the reported Vh and VL sequences of several antibodies against viruses and bacteria, the data show that many antipathogen antibodies may use the same small set of Vh genes that encode autoantibodies, but diverse VL genes that are distinct from autoantibody-related VL genes. Thus, only a small portion of the potentially functional germline Vh genes are used recurrently to generate most antibodies in a normal antibody repertoire, regardless of their reactivities with either self or non-self. PMID:1334971

  1. Splenic extrafollicular reactions and BM plasma cells sustain IgM response associated with hypercholesterolemia.

    PubMed

    Khoo, Lawrence Han Boon; Thiam, Chung Hwee; Soh, Serena Ying; Angeli, Vronique

    2015-05-01

    Hypercholesterolemia associated with atherosclerotic disease is known to be associated with increased total and oxidized (ox) low-density lipoprotein (LDL)-specific IgM antibodies in circulation. However, the B-cell responses accounting for this increase remain to be elucidated. Here, we observed an association between total IgM and oxLDL-specific IgM autoantibodies with cholesterol in the plasma of hypercholesterolemic apolipoprotein E deficient (apoE(-/-)) mice. Our findings also indicated that oxLDL-specific IgM autoantibodies production was restricted to the spleen, but not the lymph nodes. Further examination of the spleen revealed that the extrafollicular responses, but not germinal center reactions, were the dominant antibody-producing pathway. A quiescent population of IgM(+) plasma cells including oxLDL-specific IgM antibody secreting cells in BM also sustained the elevated IgM antibodies response in circulation. We determined that IgM(+) plasma cells in the BM were, at least in part, splenic derived by depleting CD11c(+) DCs and plasmablasts to disrupt the humoral responses. In addition, lowering hypercholesterolemia reduced IgM response by interfering with extrafollicular and BM responses. By elucidating the mechanism underlying the elevated IgM response observed in hypercholesterolemia, this study provides insight into novel immunotherapeutic avenues. PMID:25639537

  2. The contribution of naturally occurring IgM antibodies, IgM cross-reactivity and complement dependency in murine humoral responses to pneumococcal capsular polysaccharides.

    PubMed

    Jones, Hannah E; Taylor, Philip R; McGreal, Eamon; Zamze, Susanne; Wong, Simon Y C

    2009-09-25

    Immunogenicity of 12 capsular polysaccharides (CPS) from Streptococcus pneumoniae did not correlate with pre-existing levels of natural IgM anti-CPS antibodies in mice. Immunization of mice with individual CPS, with the exception of type 14 (the only neutral CPS tested), increased serum IgM that also bound other CPS serotypes independent of structural similarity or commonly known contaminants. Surprisingly only IgM response to type 4 (which has a small immunodominant epitope) was dependent on either complement C3 or complement receptors CD35/CD21. IgG anti-CPS responses were infrequently induced, but critically dependent on complement. Our results have clarified the role of complement in the induction of IgM and IgG anti-CPS antibody responses in mice and have implications for CPS vaccine development. PMID:19660585

  3. Light Chain Sequences of Human IgM Cold Agglutinins

    PubMed Central

    Capra, J. Donald; Kehoe, J. Michael; Williams, Ralph C.; Feizi, Ten; Kunkel, Henry G.

    1972-01-01

    The amino-terminal amino-acid sequence has been determined for the kappa light chains of nine IgM cold agglutinins with specificity for blood group-related carbohydrate antigens. Six of the nine sequences corresponded to the prototype VKIII subgroup pattern, two to that of subgroup VKII, and only one to the VKI subgroup. This distribution of kappa subgroups differs markedly from that of normal and myeloma proteins sequenced to date, where the VKI subgroup is more prevalent than either VKII or VKIII. Evidence is presented that supports the conclusion that the unusual subgroup distribution relates to the antibody property itself and not to some other attribute of these molecules. PMID:4621549

  4. Low molecular weight IgM in selective IgA deficiency.

    PubMed Central

    Kwitko, A O; Roberts-Thomson, P J; Shearman, D J

    1982-01-01

    Thirty-nine persons with selective IgA deficiency were studied. These comprised 27 subjects found by population screening and 12 by other means. Low molecular weight (LMW) serum IgM was sought in 28 of the 39 persons. Nine of the 28 (32%) had LMW IgM detectable by a sensitive gel filtration technique. Of 17 patients discovered by screening, five (29%) had LMW IgM. In the nine positive persons, LMW IgM constituted up to 17% of the total serum IgM concentration. Eight of the nine IgA deficient persons with LMW IgM, had clinical disease while associated disease in the entire IgA deficient population was less frequent. Serum immune complexes were demonstrated in five of seven subjects with LMW IgM using a C1q-dependent radioimmunoassay; four of these had immune complex associated disorders, three with polyarthritis and one with glomerulonephritis. Because circulating immune complexes are frequently detected in IgA deficient persons without disease, it is proposed that the presence of LMW serum IgM in IgA deficiency may be associated with disease due to the formation of specific pathogenic immune complexes. PMID:7172505

  5. Epithelial cells are a source of natural IgM that contribute to innate immune responses.

    PubMed

    Shao, Wenwei; Hu, Fanlei; Ma, Junfan; Zhang, Chi; Liao, Qinyuan; Zhu, Zhu; Liu, Enyang; Qiu, Xiaoyan

    2016-04-01

    Currently, natural IgM antibodies are considered to be the constitutively secreted products of B-1 cells in mice and humans. In this study, we found that mouse epithelial cells, including liver epithelial cells and small intestinal epithelial cells (IECs), could express IgM that also showed natural antibody activity. Moreover, similar to the B-1 cell-derived natural IgM that can be upregulated by TLR9 agonists (mimicking bacterial infection), the expression of epithelial cell-derived natural IgM could also be significantly increased by TLR9 signaling. More importantly, the epithelial cell-derived IgM was polyreactive, and it could recognize single-stranded DNA (ssDNA), double-stranded DNA (dsDNA), lipopolysaccharide (LPS), and insulin with low affinity; additionally, TLR9 agonists could enhance it in a MyD88-dependent manner. Furthermore, epithelial cell-derived IgM could bind various bacteria; therefore, it could be involved in anti-infection responses. Together, these results highlight the fact that epithelial cells are an important source of natural IgM, in addition to that produced by B-1 cells, and IgM contributes to the innate immune responses in local tissues, further demonstrating that the epithelium is a first line of defense in the protection against invading microbes. PMID:26820901

  6. Identification of a Novel Host-Specific IgM Protease in Streptococcus suis

    PubMed Central

    Seele, Jana; Singpiel, Alena; Spoerry, Christian; von Pawel-Rammingen, Ulrich; Valentin-Weigand, Peter

    2013-01-01

    Streptococcus suis serotype 2 is a highly invasive, extracellular pathogen in pigs with the capacity to cause severe infections in humans. This study was initiated by the finding that IgM degradation products are released after opsonization of S. suis. The objective of this work was to identify the bacterial factor responsible for IgM degradation. The results of this study showed that a member of the IdeS family, designated IdeSsuis (Immunoglobulin M-degrading enzyme of S. suis), is responsible and sufficient for IgM cleavage. Recombinant IdeSsuis was found to degrade only IgM but neither IgG nor IgA. Interestingly, Western blot analysis revealed that IdeSsuis is host specific, as it exclusively cleaves porcine IgM but not IgM from six other species, including a closely related member of the Suidae family. As demonstrated by flow cytometry and immunofluorescence microscopy, IdeSsuis modulates binding of IgM to the bacterial surface. IdeSsuis is the first prokaryotic IgM-specific protease described, indicating that this enzyme is involved in a so-far-unknown mechanism of host-pathogen interaction at an early stage of the host immune response. Furthermore, cleavage of porcine IgM by IdeSsuis is the first identified phenotype reflecting functional adaptation of S. suis to pigs as the main host. PMID:23243300

  7. IgM autoagglutinins in warm autoimmune hemolytic anemia: a poor prognostic feature.

    PubMed

    McCann, E L; Shirey, R S; Kickler, T S; Ness, P M

    1992-01-01

    The presence of both complete IgM autoagglutinins and IgG autoantibodies in warm autoimmune hemolytic anemia (AIHA) is an uncommon finding. Over a 6-year period, only 5 of 115 (4.1%) patients with AIHA had IgM and IgG autoantibodies. In 3 of the 5 cases, the complete IgM autoagglutinins reacted up to 30 degrees C and these patients responded well to corticosteroid or other therapies for warm AIHA. The 2 patients who had warm (37 degrees C) reactive IgM autoagglutinins, were refractory to corticosteroids, splenectomy and cytotoxic drugs, and died due to the complications of hemolytic anemia. The data in these 5 cases suggest that the thermal amplitude of the IgM antibody in these unusual AIHA cases may be predictive of refractoriness to therapy and poor clinical outcome. PMID:1466193

  8. The Long Elusive IgM Fc Receptor, Fc?R

    PubMed Central

    Kubagawa, Hiromi; Oka, Satoshi; Kubagawa, Yoshiki; Torii, Ikuko; Takayama, Eiji; Kang, Dong-Won; Jones, Dewitt; Nishida, Naonori; Miyawaki, Toshio; Bertoli, Luigi F.; Sanders, Sheila K.; Honjo, Kazuhito

    2014-01-01

    IgM exists as both a monomer on the surface of B cells and a pentamer secreted by plasma cells. Both preimmune natural and antigen-induced immune IgM antibodies are important for protective immunity and for immune regulation of autoimmune processes by recognizing pathogens and self-antigens. Effector proteins interacting with the Fc portion of IgM, such as complement and complement receptors, have thus far been proposed but fail to fully account for the IgM-mediated protection and regulation. A major reason for this deficit in our understanding of IgM function seems to be lack of data on a long elusive Fc receptor for IgM (Fc?R). We have recently identified a bona fide Fc?R in both humans and mice. In this article we briefly review what we have learned so far about Fc?R. PMID:24793544

  9. Type ? hyper IgM syndrome with novel mutation from India.

    PubMed

    Merchant, Rashid H; Ahmed, Javed; Ahmed, Noor; Picard, Capucine

    2014-06-01

    Hyper IgM syndrome is a primary immunodeficiency disorder characterized by normal or raised levels of immunoglobulin (Ig) M with low or absent IgG, IgA, and IgE. Five genetic causes of Hyper IgM have been identified. CD40L is deficient on T cells in Type ? Hyper IgM, leading to defective interaction between T and B lymphocytes and consequently an inability to switch from production of IgM to other classes of antibodies. This manuscript reports a patient with X linked Hyper IgM (XHIGM) syndrome caused by a novel mutation in the CD40 Ligand (CD40L) gene and a favorable outcome after bone marrow transplantation. PMID:23604614

  10. Potential impact of different cytomegalovirus (CMV) IgM assays on an algorithm requiring IgM reactivity as a criterion for measuring CMV IgG avidity.

    PubMed

    Prince, Harry E; Lap-Nixon, Mary; Brenner, Andrew; Pitstick, Nancy; Couturier, Marc Roger

    2014-06-01

    The measurement of cytomegalovirus (CMV) IgG avidity is a powerful tool for identifying individuals with recent CMV infection. Because such patients are expected to be positive for CMV IgM, several investigators have suggested that CMV IgG-positive sera first be screened for CMV IgM and then only the IgM-reactive sera be tested for avidity. We investigated the impact of different CMV IgM assays on such a reflexing algorithm using a panel of 369 consecutive IgG-positive serum samples submitted for avidity testing. A bead-based immunofluorescent assay (BIFA) identified 105 IgM-positive serum samples, whereas an IgM-capture enzyme immunoassay (EIA) identified 48 IgM-positive serum samples; this marked difference led us to evaluate additional CMV IgM assays. An enzyme-linked immunofluorescent assay (ELFA) and a chemiluminescent immunoassay (CIA) were used to test all sera with discordant BIFA/EIA results, all sera with concordant positive results, and selected sera with concordant negative results. The findings indicated that the ELFA would identify 74 CMV IgM-positive samples and the CIA would identify 64. Of the 23 low-avidity serum samples, 2 were IgM negative by BIFA, 3 by ELFA and CIA, and 4 by EIA; of the 23 intermediate-avidity serum samples, 6 were IgM negative by BIFA, 10 by ELFA, and 15 by EIA and CIA. In both these avidity groups, BIFA IgM-negative sera were also negative by the other 3 assays. These findings demonstrate that an algorithm requiring CMV IgM reactivity as a criterion for CMV IgG avidity testing does not identify all low-avidity sera and thus misses some cases of acute CMV infection. PMID:24671558

  11. Anti-HDV IgM as a Marker of Disease Activity in Hepatitis Delta

    PubMed Central

    Wranke, Anika; Heidrich, Benjamin; Ernst, Stefanie; Calle Serrano, Beatriz; Caruntu, Florin Alexandru; Curescu, Manuela Gabriela; Yalcin, Kendal; Gürel, Selim; Zeuzem, Stefan; Erhardt, Andreas; Lüth, Stefan; Papatheodoridis, George V.; Bremer, Birgit; Stift, Judith; Grabowski, Jan; Kirschner, Janina; Port, Kerstin; Cornberg, Markus; Falk, Christine S.; Dienes, Hans-Peter; Hardtke, Svenja; Manns, Michael P.; Yurdaydin, Cihan; Wedemeyer, Heiner

    2014-01-01

    Background Hepatitis delta frequently leads to liver cirrhosis and hepatic decompensation. As treatment options are limited, there is a need for biomarkers to determine disease activity and to predict the risk of disease progression. We hypothesized that anti-HDV IgM could represent such a marker. Methods Samples of 120 HDV-infected patients recruited in an international multicenter treatment trial (HIDIT-2) were studied. Anti-HDV IgM testing was performed using ETI-DELTA-IGMK-2-assay (DiaSorin). In addition, fifty cytokines, chemokines and angiogenetic factors were measured using multiplex technology (Bio-Plex System). A second independent cohort of 78 patients was studied for the development of liver-related clinical endpoints (decompensation, HCC, liver transplantation or death; median follow up of 3.0 years, range 0.6–12). Results Anti-HDV IgM serum levels were negative in 18 (15%), low (OD<0.5) in 76 (63%), and high in 26 (22%) patients of the HIDIT-2 cohort. Anti-HDV IgM were significantly associated with histological inflammatory (p<0.01) and biochemical disease activity (ALT, AST p<0.01). HDV replication was independent from anti-HDV IgM, however, low HBV-DNA levels were observed in groups with higher anti-HDV IgM levels (p<0.01). While high IP-10 (CXCL10) levels were seen in greater groups of anti-HDV IgM levels, various other antiviral cytokines were negatively associated with anti-HDV IgM. Associations between anti-HDV IgM and ALT, AST, HBV-DNA were confirmed in the independent cohort. Clinical endpoints occurred in 26 anti-HDV IgM positive patients (39%) but in only one anti-HDV IgM negative individual (9%; p = 0.05). Conclusions Serum anti-HDV IgM is a robust, easy-to-apply and relatively cheap marker to determine disease activity in hepatitis delta which has prognostic implications. High anti-HDV IgM levels may indicate an activated interferon system but exhausted antiviral immunity. PMID:25072849

  12. Diagnóstico diferencial en la encefalitis por anticuerpos contra el receptor NMDA

    PubMed Central

    González-Valcárcel, J.; Rosenfeld, M.R.; Dalmau, J.

    2011-01-01

    Resumen Introducción La encefalitis por anticuerpos contra el receptor de NMDA (NMDAR) suele desarrollarse como un síndrome característico de evolución multifásica y diagnóstico diferencial amplio. Pacientes Presentamos a 2 pacientes diagnosticadas de encefalitis por anticuerpos NMDAR con un cuadro clínico típico, pero que inicialmente señaló otras etiologías. Discusión La afectación frecuente de pacientes jóvenes con manifestaciones psiquiátricas prominentes indica frecuentemente otras consideraciones diagnósticas; las más frecuentes son las encefalitis virales, los procesos psiquiátricos y el síndrome neuroléptico maligno. Varios síndromes previamente definidos de manera parcial o descriptiva en adultos y pacientes pediátricos probablemente eran casos de encefalitis anti-NMDAR. Conclusiones La encefalitis anti-NMDAR debe considerarse en pacientes jóvenes con manifestaciones psiquiátricas subagudas, movimientos anormales y alteraciones autonómicas. La caracterización clínica e inmunológica de esta enfermedad ha llevado a la identificación de nuevos anticuerpos que afectan a procesos de memoria, aprendizaje, conducta y psicosis. PMID:20964986

  13. The new ParaDIgm: IgM from bench to clinic

    PubMed Central

    Hanala, Sherif

    2012-01-01

    The inaugural IgM event entitled “The new ParaDIgm: IgM from bench to clinic” brought together the increasingly active and growing IgM antibody community to discuss recent advances and challenges facing the discovery and development of IgM antibody therapies and technologies. Researchers, clinicians and biomanufacturing experts delivered 21 talks on the basic science and isolation of IgM, upstream and downstream development, and formulation and clinical development of the molecules. Participants networked around topics aimed at exploring the full potential of IgM antibodies. The meeting was held at DECHEMA Gesellschaft für Chemische Technik und Biotechnologie e. V. (Society for Chemical Engineering and Biotechnology), a non-profit scientific and technical society based in Frankfurt am Main, Germany. The meeting was sponsored by Patrys, Laureate Biopharma, Bio-Rad Laboratories, BIA Separations, Percivia and the Bio Affinity Company (BAC). The second New ParaDIgm: IgM from bench to clinic meeting, will be held on April 23–24, 2013 in Frankfurt, Germany. PMID:22864407

  14. Age-related aspects of human IgM(+) B cell heterogeneity.

    PubMed

    Martin, Victoria; Wu, Yu-Chang; Kipling, David; Dunn-Walters, Deborah K

    2015-12-01

    The CD27(+) IgD(+) B cell population, known as IgM memory, reduces with age. It is thought that this population is responsible for pneumococcal polysaccharide T-independent responses, and that the age-related reduction might be partially responsible for the increased susceptibility of older people to bacterial pathogens. There are other IgM(+) B cell populations that do not express IgD. We compared the different IgM populations using high-throughput sequencing of the immunoglobulin (Ig) gene repertoire and multidimensional cell phenotyping and found that the different populations of IgM cells, defined by CD27 and IgD expression, have repertoire differences. Some of these differences are likely indicative of different selection pressures in an immune response, although the older individuals were found to have a changed repertoire in naive B cells, which may contribute to some of the changes seen in memory cells. In addition, even within the CD27(+) IgD(+) IgM memory population there are multiple cell types. We show that the level of IgM expression varies substantially and hypothesize that this distinguishes between T-dependent and T-independent types of IgM memory cells. Significant age-related changes in the relative proportions of these populations may exacerbate the reduction in T-independent responders in old age. PMID:26152370

  15. Anti-GD2-like IgM autoreactivity in multiple sclerosis patients.

    PubMed

    Marconi, S; Acler, M; Lovato, L; De Toni, L; Tedeschi, E; Anghileri, E; Romito, S; Cordioli, C; Bonetti, B

    2006-06-01

    Seric IgM autoreactivity in 100 multiple sclerosis (MS) and 106 control (70 of whom had other neurological diseases) patients was assessed either by immunohistochemistry on normal human CNS tissue or to GD2, GD1a, GD3 by ELISA and thin layer chromatography (TLC) techniques. By double immunohistochemistry, we found that 44% of the total MS population showed seric IgM reactivity to oligodendrocytes and myelin, this finding being particularly frequent in patients with secondary progressive MS. In the non-MS cohort, positive signals were seen only in one patient. In all cases, extraction of lipids from CNS sections abolished the immunoreactivity. Among the gangliosides investigated by ELISA, anti-GD2-like IgM autoantibodies were detected in the serum of 30% of MS patients, a subgroup of whom (below 10%) reacted also with GD1a and/or GD3. More than 85% of MS cases with anti-GD2-like IgM immunoreactivity by ELISA showed also IgM antioligodendrocyte/myelin staining by immunohistochemistry. However, no immunostaining in MS sera was observed when gangliosides were resolved by TLC. A positive correlation with neurological disability was observed, as the Expanded Disability Status Scale of MS patients with anti-GD2-like IgM autoreactivity by ELISA was significantly worse than seronegative MS cases. The results of the present study enforce the role of glycolipids as potential autoantigens and of IgM autoantibodies in MS pathogenesis. PMID:16764343

  16. IgM nephropathy; can we still ignore it

    PubMed Central

    Vanikar, Aruna

    2013-01-01

    Context:IgM nephropathy (IgMN) is a relatively less recognized clinico-immunopathological entity in the domain of glomerulonephritis , often thought to be a bridge between minimal change disease and focal segmental glomerulosclerosis. Evidence Acquisitions: Directory of Open Access Journals (DOAJ), Google Scholar, Pubmed (NLM), LISTA (EBSCO) and Web of Science has been searched. Results: IgM nephropathy can present as nephritic syndrome or less commonly with subnephrotic proteinuria or rarely hematuria. About 30% patients respond to steroids whereas others are steroid dependent / resistant. They should be given a trial of Rituximab or stem cell therapy. Conclusions:IgM nephropathy (IgMN) is an important and rather neglected pathology responsible for renal morbidity in children and adults in developing countries as compared to developed nations with incidence of 2-18.5% of native biopsies. Abnormal T-cell function with hyperfunctioning suppressor T-cells are believed to be responsible for this disease entity. Approximately one third of the patients are steroid responders where as the remaining two thirds are steroid resistant or dependent. Therapeutic trials including cell therapies targeting suppressor T-cells are required. PMID:24475434

  17. Expression and glycoengineering of functionally active heteromultimeric IgM in plants.

    PubMed

    Loos, Andreas; Gruber, Clemens; Altmann, Friedrich; Mehofer, Ulrich; Hensel, Frank; Grandits, Melanie; Oostenbrink, Chris; Stadlmayr, Gerhard; Furtmller, Paul G; Steinkellner, Herta

    2014-04-29

    IgM antibodies are an important player of the human's innate defense mechanisms and increasingly have gained interest as therapeutics. Although the expression of IgM antibodies in mammalian cell culture is established, this approach remains costly and alternative methods have not been developed yet. Plants have a proven record for the production of therapeutically relevant recombinant proteins. However, whether they are able to express proteins like IgM antibodies, which range among the most complex human proteins, remains unknown so far. Here we report the in planta generation of the functionally active monoclonal antitumor IgM PAT-SM6 (SM6). SM6 efficiently accumulates in plant leaves and assembles correctly into heterooligomers (pentamers and hexamers). Detailed glycosylation analysis exhibited complex and oligomannosidic N-glycans in a site-specific manner on human-serum IgM and on plant- and human-cell-line-produced SM6. Moreover, extensive in planta glycoengineering allowed the generation of SM6 decorated with sialylated human-type oligosaccharides, comparable to plasma-derived IgM. A glycosylated model of pentameric IgM exhibits different accessibility of the glycosylation sites, explaining site-specific glycosylation. Biochemical and biophysical properties and importantly biological activities of plant-derived SM6 glycoforms are comparable to the human-cell-derived counterparts. The in planta generation of one of the most complex human proteins opens new pathways toward the production of difficult-to-express proteins for pharmaceutical applications. Moreover, the generation of IgMs with a controlled glycosylation pattern allows the study of the so far unknown contribution of sugar moieties to the function of IgMs. PMID:24706782

  18. Expression and glycoengineering of functionally active heteromultimeric IgM in plants

    PubMed Central

    Loos, Andreas; Gruber, Clemens; Altmann, Friedrich; Mehofer, Ulrich; Hensel, Frank; Grandits, Melanie; Oostenbrink, Chris; Stadlmayr, Gerhard; Furtmüller, Paul G.; Steinkellner, Herta

    2014-01-01

    IgM antibodies are an important player of the human’s innate defense mechanisms and increasingly have gained interest as therapeutics. Although the expression of IgM antibodies in mammalian cell culture is established, this approach remains costly and alternative methods have not been developed yet. Plants have a proven record for the production of therapeutically relevant recombinant proteins. However, whether they are able to express proteins like IgM antibodies, which range among the most complex human proteins, remains unknown so far. Here we report the in planta generation of the functionally active monoclonal antitumor IgM PAT-SM6 (SM6). SM6 efficiently accumulates in plant leaves and assembles correctly into heterooligomers (pentamers and hexamers). Detailed glycosylation analysis exhibited complex and oligomannosidic N-glycans in a site-specific manner on human-serum IgM and on plant- and human-cell-line–produced SM6. Moreover, extensive in planta glycoengineering allowed the generation of SM6 decorated with sialylated human-type oligosaccharides, comparable to plasma-derived IgM. A glycosylated model of pentameric IgM exhibits different accessibility of the glycosylation sites, explaining site-specific glycosylation. Biochemical and biophysical properties and importantly biological activities of plant-derived SM6 glycoforms are comparable to the human-cell–derived counterparts. The in planta generation of one of the most complex human proteins opens new pathways toward the production of difficult-to-express proteins for pharmaceutical applications. Moreover, the generation of IgMs with a controlled glycosylation pattern allows the study of the so far unknown contribution of sugar moieties to the function of IgMs. PMID:24706782

  19. Transcriptional Heterogeneity of IgM+ Cells in Rainbow Trout (Oncorhynchus mykiss) Tissues

    PubMed Central

    Abós, Beatriz; Castro, Rosario; Pignatelli, Jaime; Luque, Alfonso; González, Lucia; Tafalla, Carolina

    2013-01-01

    Two major classes of B lymphocytes have been described to date in rainbow trout: IgM+ and IgT+ cells. IgM+ cells are mainly localized in the spleen, peripheral blood and kidney but are also found in other tissues. However, differences among IgM+ cell populations attending to its location are poorly defined in fish. Thus, the aim of this work was to characterize the expression of different immune molecules such as chemokine receptors, Toll-like receptors (TLRs) and transcription factors on sorted IgM+ lymphocytes from different rainbow trout tissues. IgM+ populations from blood, spleen, kidney, gills, intestine and liver were isolated by cell sorting and the constitutive levels of transcription of these genes evaluated by real-time PCR. To further characterize B cells, we identified an MS4A sequence. In humans, the MS4A family includes several genes with immune functions, such as the B cell marker CD20 or FcRβ. Subsequently, we have also evaluated the mRNA levels of this MS4A gene in the different IgM+ populations. The relevant differences in transcriptional patterns observed for each of these IgM+ populations analyzed, point to the presence of functionally different tissue-specific B cell populations in rainbow trout. The data shown provides a pattern of genes transcribed in IgM+ B cells not previously revealed in teleost fish. Furthermore, the constitutive expression of all the TLR genes analyzed in IgM+ cells suggests an important role for these cells in innate immunity. PMID:24324826

  20. IgM Myeloma or Waldenstrom's Macroglobulinemia Is the Big Question?

    PubMed Central

    BHATT, Vijaya Raj; MURUKUTLA, Srujitha; NAQI, Muniba; PANT, Shradha; KEDIA, Shiksha; TERJANIAN, Terenig

    2014-01-01

    Although critical from therapeutic and prognostic perspectives, differentiating IgM Myeloma (MM) from Waldenstrom's macroglobulinemia (WM) is fraught with failure. WM can usually be distinguished from IgM MM by the lymphoplasmacytic versus pure plasmacytic morphology, absent versus present lytic bone lesions, and immunophenotypic findings. However, all these features have their own limitations; hence, it requires constant vigilance and periodic re-evaluation. Here we describe a case of a 70-year-old woman initially diagnosed as smoldering IgM MM, who eventually turned out to have WM. PMID:25553130

  1. Cytomegalovirus IgM Seroprevalence among Women of Reproductive Age in the United States

    PubMed Central

    Wang, Chengbin; Dollard, Sheila C.; Amin, Minal M.; Bialek, Stephanie R.

    2016-01-01

    Cytomegalovirus (CMV) IgM indicates recent active CMV infection. CMV IgM seroprevalence is a useful marker for prevalence of transmission. Using data from the National Health and Nutrition Examination Survey (NHANES) III 1988–1994, we present estimates of CMV IgM prevalence by race/ethnicity, provide a comparison of IgM seroprevalence among all women and among CMV IgG positive women, and explore factors possibly associated with IgM seroprevalence, including socioeconomic status and exposure to young children. There was no difference in IgM seroprevalence by race/ethnicity among all women (3.1%, 2.2%, and 1.6% for non-Hispanic white, non-Hispanic black and Mexican American, respectively; P = 0.11). CMV IgM seroprevalence decreased significantly with increasing age in non-Hispanic black women (P<0.001 for trend) and marginally among Mexican American women (P = 0.07), while no apparent trend with age was seen in non-Hispanic white women (P = 0.99). Among 4001 IgG+ women, 118 were IgM+, resulting in 4.9% IgM seroprevalence. In IgG+ women, IgM seroprevalence varied significantly by age (5.3%, 7.3%, and 3.7% for women of 12–19, 20–29, and 30–49 years; P = 0.04) and race/ethnicity (6.1%, 2.7%, and 2.0% for non-Hispanic white, non-Hispanic black, and Mexican American; P<0.001). The factors reported associated with IgG seroprevalence were not associated with IgM seroprevalence. The patterns of CMV IgM seroprevalence by age, race/ethnicity, and IgG serostatus may help understanding the epidemiology of congenital CMV infection as a consequence of vertical transmission and are useful for identifying target populations for intervention to reduce CMV transmission. PMID:26990759

  2. Suppressor T cells prevent in vitro expression of IgM rheumatoid factor in some healthy adults

    SciTech Connect

    Koopman, W.J.

    1981-12-01

    Peripheral blood mononuclear leukocytes (MNL) from 11 of 30 healthy adults elaborated detectable IgM RF when stimulated with pokeweed mitogen. The influence of T cells on IgM RF production by autologous B Cells prepared from donors whose unfractionated MNL synthesized IgM RF in response to PMW was investigated. Untreated T cells supported IgM RF production by autologous B cells with optimal synthesis observed at T:B cell ratios of 2:1 at higher T:B cell ratios a decline in IgM RF production occurred. In contrast, at higher T:B cell ratios irradiated T cells supported consistently higher levels of IgM RF production than untreated T cells suggesting the presence of radiosensitive suppressor T cells for IgM RF in these individuals. Irridiated T cells were compared to untreated T cells for capacity to support IgM RF production by autologous B cells from 12 randomly selected donors at T:B cell ratios of 3:1. Untreated T cells from 4 of 12 individuals were capable of cooperating in induction of IgM RF production by autologous B cells, whereas irradiated T cells supported IgM RF production in 6 of 12 individuals. Levels of IgM RF production in all 6 individuals were significantly higher with irradiated T cells than with untreated T cells; in 2 individuals IgM RF synthesis by autologous B cells was observed only in the presence of irradiated T cells. In 4 of 6 individuals increases in the ratio of IgM RF total IgM synthesis occured with irradiated T cells (when compared to untreated T cells), suggesting disproportionate suppression of RF production. These results indicate the presence of radiosensitive T cells capable of suppressing IgM RF production in a significant fraction of healthy adults and raise the possibility that these cells may regulate in vivo expression of RF.

  3. Comparative Accuracy of the InBios Scrub Typhus Detect IgM Rapid Test for the Detection of IgM Antibodies by Using Conventional Serology

    PubMed Central

    Kingston, Hugh W. F.; Blacksell, Stuart D.; Tanganuchitcharnchai, Ampai; Laongnualpanich, Achara; Basnyat, Buddha; Day, Nicholas P. J.

    2015-01-01

    This study investigated the comparative accuracy of a recombinant 56-kDa type-specific antigen-based rapid diagnostic test (RDT) for scrub typhus for the detection of IgM antibodies by using conventional serology in well-characterized serum samples from undifferentiated febrile illness patients. The RDT showed high specificity and promising comparative accuracy, with 82% sensitivity and 98% specificity for samples defined positive at an IgM indirect immunofluorescence assay positivity cutoff titer of ?1:1,600 versus 92% and 95% at ?1:6,400, respectively. PMID:26291089

  4. Comparative Accuracy of the InBios Scrub Typhus Detect IgM Rapid Test for the Detection of IgM Antibodies by Using Conventional Serology.

    PubMed

    Kingston, Hugh W F; Blacksell, Stuart D; Tanganuchitcharnchai, Ampai; Laongnualpanich, Achara; Basnyat, Buddha; Day, Nicholas P J; Paris, Daniel H

    2015-10-01

    This study investigated the comparative accuracy of a recombinant 56-kDa type-specific antigen-based rapid diagnostic test (RDT) for scrub typhus for the detection of IgM antibodies by using conventional serology in well-characterized serum samples from undifferentiated febrile illness patients. The RDT showed high specificity and promising comparative accuracy, with 82% sensitivity and 98% specificity for samples defined positive at an IgM indirect immunofluorescence assay positivity cutoff titer of ?1:1,600 versus 92% and 95% at ?1:6,400, respectively. PMID:26291089

  5. [Comparison of methods for the demonstration of Treponema-specific IgM].

    PubMed

    Panuccio, A; Borroni, G; Gelosa, L

    1989-01-01

    In this research 113 sera have been analysed with three methods for IgM treponema-specific determination: IgM-SPHA, IgM-EIA and 19S IgM FTA-ABS. Among these sera, 33 samples related to non-treated patients at different stages of infection, and 80 samples to treated patients. The results point out a light sensibility of the IgM-SPHA in primary lues. The IgM-EIA test has performed a good specificity, but displayed a sensibility lower to the 19S IgM FTA-ABS, which proved the best of tests. About the cases of treated lues at different stages, in 23 samples with VDRL negative has been found no positivity at three tests used, while in 49 samples with VDRL positive 8 are resulted positive at 19S IgM FTA-ABS. PMID:2518811

  6. Circulating IgM Requires Plasma Membrane Disruption to Bind Apoptotic and Non-Apoptotic Nucleated Cells and Erythrocytes

    PubMed Central

    Hesketh, Emily E.; Dransfield, Ian; Kluth, David C.; Hughes, Jeremy

    2015-01-01

    Autoimmunity is associated with defective phagocytic clearance of apoptotic cells. IgM deficient mice exhibit an autoimmune phenotype consistent with a role for circulating IgM antibodies in apoptotic cell clearance. We have extensively characterised IgM binding to non-apoptotic and apoptotic mouse thymocytes and human Jurkat cells using flow cytometry, confocal imaging and electron microscopy. We demonstrate strong specific IgM binding to a subset of Annexin-V (AnnV)+PI (Propidium Iodide)+ apoptotic cells with disrupted cell membranes. Electron microscopy studies indicated that IgM+AnnV+PI+ apoptotic cells exhibited morphologically advanced apoptosis with marked plasma membrane disruption compared to IgM-AnnV+PI+ apoptotic cells, suggesting that access to intracellular epitopes is required for IgM to bind. Strong and comparable binding of IgM to permeabilised non-apoptotic and apoptotic cells suggests that IgM bound epitopes are 'apoptosis independent' such that IgM may bind any cell with profound disruption of cell plasma membrane integrity. In addition, permeabilised erythrocytes exhibited significant IgM binding thus supporting the importance of cell membrane epitopes. These data suggest that IgM may recognize and tag damaged nucleated cells or erythrocytes that exhibit significant cell membrane disruption. The role of IgM in vivo in conditions characterized by severe cell damage such as ischemic injury, sepsis and thrombotic microangiopathies merits further exploration. PMID:26121639

  7. Platelet antibodies of the IgM class in immune thrombocytopenic purpura

    SciTech Connect

    Cines, D.B.; Wilson, S.B.; Tomaski, A.; Schreiber, A.D.

    1985-04-01

    The clinical course and response to therapy of patients with immune thrombocytopenic purpura (ITP) are not completely determined by the level of IgG present on the platelet surface. It is possible that antibodies of other immunoglobulin classes also play a role in platelet destruction in some of these patients. Therefore, the authors studied 175 patients with ITP for the presence of IgM anti-platelet antibodies using radiolabeled polyclonal or monoclonal anti-IgM. They observed that 57% of patients with clinical ITP had increased levels of IgM on their platelets, compared with normal controls and patients with thrombocytopenia who did not have ITP. They obtained similar results using either radiolabeled polyclonal or monoclonal anti-IgM, reagents whose integrity was first characterized using erythrocytes coated with defined amounts of IgM antibody. Among patients with increased platelet-IgM there was a significant correlation both with the presence of increased platelet-C3 as well as the amount of platelet-C3. The authors demonstrated the presence of warm-reacting IgM anti-platelet antibodies in the plasma of two of these patients who were further studied. These studies demonstrate the presence of warm-reacting IgM anti-platelet antibodies in some patients with ITP. They suggest that the binding of complement to platelets by IgM antibodies may initiate platelet clearance as well as enhance the effect of IgG antibodies in ITP.

  8. Emerging Functions of Natural IgM and Its Fc Receptor FCMR in Immune Homeostasis

    PubMed Central

    Wang, Hongsheng; Coligan, John E.; Morse, Herbert C.

    2016-01-01

    Most natural IgM antibodies are encoded by germline Ig sequences and are produced in large quantities by both mice and humans in the absence of intentional immunization. Natural IgM are reactive with many conserved epitopes, including those shared by microorganisms and autoantigens. As a result, these antibodies play important roles in clearing intruding pathogens, as well as apoptotic/necrotic cells and otherwise damaged tissues. While natural IgM binds to target structures with low affinity due to a lack of significant selection by somatic hypermutation, its pentameric structure with 10 antigen-binding sites enables these antibodies to bind multivalent target antigens with high avidity. Opsonization of antigen complexed with IgM is mediated by cell surface Fc receptors. While the existence of Fc alpha/mu receptor has been known for some time, only recently has the Fc receptor specific for IgM (FCMR) been identified. In this review, we focus on our current understandings of how natural IgM and FCMR regulate the immune system and maintain homeostasis under physiological and pathological conditions. PMID:27014278

  9. Physiological IgM Class Catalytic Antibodies Selective for Transthyretin Amyloid*

    PubMed Central

    Planque, Stephanie A.; Nishiyama, Yasuhiro; Hara, Mariko; Sonoda, Sari; Murphy, Sarah K.; Watanabe, Kenji; Mitsuda, Yukie; Brown, Eric L.; Massey, Richard J.; Primmer, Stanley R.; O'Nuallain, Brian; Paul, Sudhir

    2014-01-01

    Peptide bond-hydrolyzing catalytic antibodies (catabodies) could degrade toxic proteins, but acquired immunity principles have not provided evidence for beneficial catabodies. Transthyretin (TTR) forms misfolded β-sheet aggregates responsible for age-associated amyloidosis. We describe nucleophilic catabodies from healthy humans without amyloidosis that degraded misfolded TTR (misTTR) without reactivity to the physiological tetrameric TTR (phyTTR). IgM class B cell receptors specifically recognized the electrophilic analog of misTTR but not phyTTR. IgM but not IgG class antibodies hydrolyzed the particulate and soluble misTTR species. No misTTR-IgM binding was detected. The IgMs accounted for essentially all of the misTTR hydrolytic activity of unfractionated human serum. The IgMs did not degrade non-amyloidogenic, non-superantigenic proteins. Individual monoclonal IgMs (mIgMs) expressed variable misTTR hydrolytic rates and differing oligoreactivity directed to amyloid β peptide and microbial superantigen proteins. A subset of the mIgMs was monoreactive for misTTR. Excess misTTR was dissolved by a hydrolytic mIgM. The studies reveal a novel antibody property, the innate ability of IgMs to selectively degrade and dissolve toxic misTTR species as a first line immune function. PMID:24648510

  10. The role of IgM rheumatoid factor in experimental immune vasculitis.

    PubMed Central

    Floyd, M; Tesar, J T

    1979-01-01

    The effect of IgM rhematoid factor (RF) on reversepassive cutaneous Arthus reaction in rats was studied. The RF was obtained from the serum cryoglobulin of a patient with symptoms of purpura, arthralgia and digital gangrene. The cryoglobulins was of IgG-IgM type and when given i.v it induced a prompt hypocomplementaemia in experimental animals. The purified RF also induced low serum complement levels when injected i.v. along with complexes of non-complement-fixing, aggregated IgG. A reverse passive Arthus reaction was induced by intradermal injection of IgG anti-bovine serum albumin (BSA), followed by an i.v. dose of antigen (Ag). The cutaneous inflammatory reaction was aggravated by simultaneous administration of IgM RF intradermally, but not by IgM without antibody (Ab) properties. Intradermal injection of low concentrations of non-complement-fixing IgG anti-BSA, along with normal human IgM, followed by i.v. injection of BSA, resulted in a complete lack of cutaneous inflammation. At higher Ab concentrations there was only a mild inflammation. However, when IgM RF was substituted for normal IgM and injected with non-complement-fixing anti-BSA, an effective reverse passive cutaneous Arthus reaction and vasculitis was induced. The inflammatory response was greatly suppressed by decomplementation of animals by cobra venom factor. This study provides evidence favouring an inflammatory, complement-dependent role for RF in vasculitis. PMID:157238

  11. Unique Ligand-Binding Property of the Human IgM Fc Receptor (Fc?R)

    PubMed Central

    Honjo, Kazuhito; Kubagawa, Yoshiki; Kearney, John F.; Kubagawa, Hiromi

    2016-01-01

    The IgM Fc receptor (Fc?R) is the newest FcR and co-ligation of Fc?R and Fas/CD95 on Jurkat cells with agonistic IgM anti-Fas mAb was shown to inhibit Fas-induced apoptosis. The ligand-binding activity of human Fc?R was further examined. Fc?R-mediated protection from apoptosis was partially blocked by addition of 104 molar excess of IgM or its soluble immune complexes, but could be inhibited by addition of 10-fold excess of IgM anti-CD2 mAb. This suggests that Fc?R binds more efficiently to the Fc portion of IgM reactive with plasma-membrane proteins than to the Fc portion of IgM in solution. The former interaction occurred in cis on the same cell surface, but not in trans between neighboring cells. This cis engagement of Fc?R resulted in modulation of Ca2+ mobilization via CD2 on Jurkat cells or BCR on blood B cells upon cross-linkage with the corresponding IgM mAbs. Several functional changes were observed with Fc?R-mutants: (i) significant increase in IgM-ligand binding in the cytoplasmic tail-deletion mutant; (ii) enhanced cap formation in Fc?R upon IgM binding at 4C with a point mutation of the transmembrane His to Phe; and (iii) less protective activity of Fc?R in IgM anti-Fas mAb-mediated apoptosis assays with a point mutation of the membrane-proximal Tyr to Phe. These findings show the importance of the cis engagement of Fc?R and its critical role in receptor function; hence, Fc?R on B-, T- and NK-cells may modulate the function of surface proteins recognized by natural or immune IgM Abs on the shared membrane cell-surface. PMID:25601920

  12. J chain synthesis and secretion of hexameric IgM is differentially regulated by lipopolysaccharide and interleukin 5.

    PubMed Central

    Randall, T D; Parkhouse, R M; Corley, R B

    1992-01-01

    Two functional polymeric forms of IgM can be produced by antibody-secreting B cells. Hexameric IgM lacks detectable J (joining) chain and activates complement 17-fold better than pentameric IgM, which usually contains one J chain per pentamer. Using the inducible B-cell lymphoma CH12, we determined if the synthesis of a particular polymeric form of IgM is a fixed property of B cells or can be altered. Lipopolysaccharide (LPS)-stimulated CH12 cells produced mixtures of IgM hexamers and pentamers, resulting in antibody with high complement-fixing activity. In contrast, interleukin-5-stimulated CH12 cells secreted predominantly pentameric IgM, with a correspondingly lower lytic activity. Differences in lytic activity were due only to the amount of hexameric IgM in the secreted antibody. Interleukin 5 stimulated higher production of J chain RNA and protein than LPS, while LPS induced the highest levels of the secretory form of mu protein. The amount of hexameric IgM secreted was therefore inversely proportional to the level of intracellular J chain protein in the responding B cells. We conclude that the biologic function of IgM produced by B cells differs depending on how they are stimulated and that this difference may be regulated by the relative availabilities of J chain and secretory mu proteins during IgM polymerization. Images PMID:1736312

  13. Functional characterization of IgM+ B cells and adaptive immunity in lumpfish (Cyclopterus lumpus L.).

    PubMed

    Rnneseth, Anita; Ghebretnsae, Dawit B; Wergeland, Heidrun I; Haugland, Gyri T

    2015-10-01

    The innate immune responses in lumpfish (Cyclopterus lumpus L.) have been shown to be functional, but little is currently known about the B cells, immunoglobulins or adaptive immune responses in this species. We have used anti-IgM antiserum to isolate B cells and compared them morphologically and functionally with other cell types. The fraction of IgM(+) cells among isolated peripheral blood leukocytes (PBL), head kidney leukocytes (HKL) and spleen leukocytes (SL) was in the range of 40%, 12% and 34%, respectively. The IgM(+) B cells had high phagocytic ability and were the predominant phagocytes in blood with higher capacity than IgM(+) B cells in HKL. Interestingly, among PBL, the most potent phagocytes were, in addition to monocytes, some small agranular uncharacterized IgM(-) cells. The IgM(+) B cells were positive for acid phosphatases (AcP), but negative for myeloperoxidase (MPO). Neutrophils were positive for MPO, while monocytes/macrophages and dendritic-like cells stained negatively. Monocytes/macrophages and the small, agranular IgM(-) cells stained most strongly positive for AcP corresponding to their high phagocytic capacity. Further, the ability to produce specific antibodies upon immunization verified adaptive immunity in the species. The high proportion of phagocytic IgM(+) B cells and their phagocytic ability indicate a significant role of phagocytic B cells in lumpfish innate immunity. The present analyses also give strong indications that vaccination and immunostimulation of farmed lumpfish can be used to prevent disease and mortality caused by pathogenic organisms. PMID:26021455

  14. Influenza Virus-Specific Neutralizing IgM Antibodies Persist for a Lifetime

    PubMed Central

    Skountzou, Ioanna; Satyabhama, Lakshmipriyadarshini; Stavropoulou, Anastasia; Ashraf, Zuhha; Esser, E. Stein; Vassilieva, Elena; Koutsonanos, Dimitrios; Compans, Richard

    2014-01-01

    Detection of immunoglobulin M (IgM) antibodies has long been used as an important diagnostic tool for identifying active viral infections, but their relevance in later stages has not been clearly defined in vivo. In this study, we followed the kinetics, longevity, and function of influenza virus-specific IgM antibodies for 2 years following sublethal infection of mice with live mouse-adapted A/PR/8/34 virus or immunization with formalin-inactivated virus. These groups mounted robust protective immune responses and survived lethal challenges with 50× 50% lethal dose (LD50) mouse-adapted A/PR/8/34 virus 600 days after the primary exposure. Surprisingly, the virus-specific IgM antibodies persisted along with IgG antibodies, and we found a significantly higher number of IgM-positive (IgM+) virus-specific plasma cells than IgG+ plasma cells that persisted for at least 9 months postexposure. The IgM antibodies were functional as they neutralized influenza virus in the presence of complement just as well as IgG antibodies did. PMID:25165027

  15. The Omentum Is a Site of Protective IgM Production during Intracellular Bacterial Infection

    PubMed Central

    Jones, Derek D.; Racine, Rachael; Wittmer, Susan T.; Harston, Louise; Papillion, Amber M.; Dishaw, Lisa M.; Randall, Troy D.; Woodland, David L.

    2015-01-01

    Infection of mice with the bacterium Ehrlichia muris elicits a protective T cell-independent (TI) IgM response mediated primarily by a population of CD11c-expressing plasmablasts in the spleen. Although splenic marginal zone (MZ) B cells are considered to be important for TI responses to blood-borne pathogens, MZ B cells were not responsible for generating plasmablasts in response to Ehrlichia muris. Moreover, antigen-specific serum IgM was decreased only modestly in splenectomized mice and in mice that lacked spleen, lymph nodes, and Peyer's patches (SLP mice). Both splenectomized and SLP mice were protected against lethal ehrlichial challenge infection. Moreover, we found a high frequency of Ehrlichia-specific plasmablasts in the omentum of both conventional and SLP mice. Omental plasmablasts elicited during Ehrlichia infection lacked expression of CD138 but expressed CD11c in a manner similar to that of their splenic counterparts. Selective ablation of CD11c-expressing B cells nearly eliminated the omental Ehrlichia-specific plasmablasts and reduced antigen-specific serum IgM, identifying the omental B cells as a source of IgM production in the SLP mice. Generation of the omental plasmablasts was route dependent, as they were detected following peritoneal infection but not following intravenous infection. Our data identify the omentum as an important auxiliary site of IgM production during intracellular bacterial infection. PMID:25776744

  16. Natural IgM: Beneficial autoantibodies for the control of inflammatory and autoimmune disease?

    PubMed Central

    Grnwall, Caroline; Silverman, Gregg J.

    2014-01-01

    Natural IgM are highly represented in the circulation at birth, and these often autoreactive antibodies have been postulated to have innate-like properties and play crucial roles in apoptotic cell clearance, tissue homeostasis, and immune modulation. This review summarizes the known properties of these IgM autoantibodies, and the evidence that these anti-apoptotic cell IgM natural antibodies can regulate inflammatory responses through ancient pathways of the innate immune system that first arose long before the initial emergence of the adaptive immune system. While the regulatory contributions of these natural IgM autoantibodies are certainly not an essential and fundamental component of host defenses, these provide an additional layer to further protect the host. More importantly, these IgM antibody responses are highly inducible and their up-regulation can be a powerful means for the host to survive in a setting of chronic inflammation. The observed beneficial clinical associations for cardiovascular disease and autoimmunity, as well as opportunities for potential therapeutic implications are discussed. PMID:24691998

  17. West Nile virus IgM and IgG antibodies three years post- infection

    PubMed Central

    Papa, A; Anastasiadou, A; Delianidou, M

    2015-01-01

    Background: West Nile virus (WNV) causes to humans a variety of symptoms, from asymptomatic infection to severe neuroinvasive disease. In a previous study, it was shown that WNV IgM antibodies persisted in three of 26 (12%) patients, nine months after onset of the symptoms. The aim of the present study was to test 10 of these patients, three years post-infection for probable persistence of IgM antibodies and to investigate their IgG antibody patterns. Material and Methods: In summer 2013 serum samples were collected from 10 persons who were infected with WNV in 2010; 6 of them had a neuroinvasive disease. The three persons with detectable WNV IgM antibodies, nine months after onset of the symptoms, were included in the study. All samples were tested by ELISA in parallel with their stored paired samples taken in 2011. The positive results were confirmed by neutralization test. Results: WNV IgM antibodies were still detectable in the three persons, while high levels of WNV IgG and neutralizing antibodies were present in nine of the 10 persons, regardless the involvement of the nervous system. Conclusions: WNV IgM antibodies persist for more than three years in 12% of patients with WNV infection, while WNV IgG antibodies persist and even increase their levels, regardless the involvement of the nervous system, suggesting that the immune response in the symptomatic WNV infections is strong and long-lasting. Hippokratia 2015, 19 (1): 34-36. PMID:26435644

  18. Roles of heavy and light chains in IgM polymerization.

    PubMed Central

    Bornemann, K D; Brewer, J W; Beck-Engeser, G B; Corley, R B; Haas, I G; Jäck, H M

    1995-01-01

    IgM antibodies are secreted as multisubunit polymers that consist of as many as three discrete polypeptides: mu heavy chains, light (L) chains, and joining (J) chains. We wished to determine whether L chains that are required to confer secretory competence on immunoglobulin molecules must be present for IgM to polymerize--that is, for intersubunit disulfide bonds to form between mu chains. Using a L-chain-loss variant of an IgM-secreting hybridoma, we demonstrated that mu chains were efficiently polymerized independent of L chains, in a manner similar to that observed for conventional microL complexes, and that the mu polymers incorporated J chain. These mu polymers were not secreted but remained associated with the endoplasmic reticulum-resident chaperone BiP (GRP78). This finding is consistent with the endoplasmic reticulum being the subcellular site of IgM polymerization. We conclude that mu chain alone has the potential to direct the polymerization of secreted IgM, a process necessary but not sufficient for IgM to attain secretory competence. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:7761423

  19. New 21 cm Power Spectrum Upper Limits From PAPER II: Constraints on IGM Properties at z = 7.7

    NASA Astrophysics Data System (ADS)

    Pober, Jonathan; Ali, Zaki; Parsons, Aaron; Paper Team

    2015-01-01

    Using a simulation-based framework, we interpret the power spectrum measurements from PAPER of Ali et al. in the context of IGM physics at z = 7.7. A cold IGM will result in strong 21 cm absorption relative to the CMB and leads to a 21 cm fluctuation power spectrum that can exceed 3000 mK^2. The new PAPER measurements allow us to rule out extreme cold IGM models, placing a lower limit on the physical temperature of the IGM. We also compare this limit with a calculation for the predicted heating from the currently observed galaxy population at z = 8.

  20. Diagnostic and prognostic significance of the IgM antibody to the Hepatitis delta virus

    SciTech Connect

    Farci, P.; Gerin, J.L.; Aragona, M.; Lindsey, I.; Crivelli, O.; Balestrieri, A.; Smedile, A.; Thomas, H.C.; Rizzetto, M.

    1986-03-21

    The IgM class antibody to the hepatitis delta virus (HDV) was determined in different clinical categories of hepatitis B surface antigen carriers infected by the HDV (positive in the test for total antibody to HDV). The IgM antibody was found at high titers in each 70 patients with inflammatory liver disease and at a low titer in one six patients with inactive cirrhosis; it was not found in eight carriers with normal liver histology. Testing for Igm antibody to HDV distinguishes hepatitis B surface antigen carriers who have underlying inflammatory HDV liver disease from those with past HDV infection and provides prognostic information on the course of chronic HDV hepatitis.

  1. Reversal of IgM deficiency following a gluten-free diet in seronegative celiac disease.

    PubMed

    Montenegro, Lucia; Piscitelli, Domenico; Giorgio, Floriana; Covelli, Claudia; Fiore, Maria Grazia; Losurdo, Giuseppe; Iannone, Andrea; Ierardi, Enzo; Di Leo, Alfredo; Principi, Mariabeatrice

    2014-12-14

    Selective IgM deficiency (sIGMD) is very rare; it may be associated with celiac disease (CD). We present the case of an 18-year-old man with sIGMD masking seronegative CD. Symptoms included abdominal pain, diarrhea and weight loss. Laboratory tests showed reduced IgM, DQ2-HLA and negative anti-transglutaminase. Villous atrophy and diffuse immature lymphocytes were observed at histology. Tissue transglutaminase mRNA mucosal levels showed a 6-fold increase. The patient was treated with a gluten-free diet (GFD) and six months later the symptoms had disappeared, the villous architecture was restored and mucosal tissue transglutaminase mRNA was comparable to that of healthy subjects. After 1 year of GFD, a complete restoration of normal IgM values was observed and duodenal biopsy showed a reduction of immature lymphocytes and normal appearance of mature immune cells. PMID:25516687

  2. Characterization of the receptor for IgM present on human B lymphocytes.

    PubMed Central

    Burns, G F; Cawley, J C; Barker, C R

    1979-01-01

    The presence of a receptor for the Fc of IgM (muFcR) was demonstrated on the pathological B cells of all of sixteen patients with hairy-cell leukaemia and most, but not all, of twenty-four cases of chronic lymphocytic leukaemia, by a rosette method employing ox erythrocytes sensitized with purified IgM (EAm). This muFcR was also demonstrated on a small population of normal human mononuclear cells from peripheral blood. Pathological B cells with this receptor (Bm) simultaneously expressed a different and distinct receptor for the Fc of IgG, and were detectable without preincubation in medium containing foetal calf serum (FCS). The muFcR on B cells was blocked by Fc5mu and IgM, but not by F(ab')2mu fragments, or by IgG, whether monomeric or aggregated. Monomeric IgM and IgM bound to its antigen blocked much more effectively than pentameric IgM. B cells also possessed surface immunoglobulin and the Ia-like P29, 34 antigen, and an antiserum to this antigen blocked the muFcR. The muFcR on B cells differs in a number of ways from the muFcR reported on T cells, and these differential characteristics are discussed in some detail. The muFcR was rapidly shed and resynthesized when washed Bm cells were maintained in medium not containing FCS and the general importance of this phenomenon in any study of muFcR is considered. It is suggested that Bm cells are memory cells and that the muFcR plays a part in the immune response. Images Figure 2 PMID:312263

  3. Antagonism of cannabinoid receptor 2 pathway suppresses IL-6-induced immunoglobulin IgM secretion

    PubMed Central

    2014-01-01

    Background Cannabinoid receptor 2 (CB2) is expressed predominantly in the immune system, particularly in plasma cells, raising the possibility that targeting the CB2 pathway could yield an immunomodulatory effect. Although the role of CB2 in mediating immunoglobulin class switching has been reported, the effects of targeting the CB2 pathway on immunoglobulin secretion per se remain unclear. Methods Human B cell line SKW 6.4, which is capable of differentiating into IgM-secreting cells once treated with human IL-6, was employed as the cell model. SKW 6.4 cells were incubated for 4 days with CB2 ligands plus IL-6 (100 U/ml). The amount of secreted IgM was determined by an ELISA. Cell proliferation was determined by the 3H-Thymidine incorporation assay. Signal molecules involved in the modulation of IgM secretion were examined by real-time RT-PCR and Western blot analyses or by using their specific inhibitors. Results We demonstrated that CB2 inverse agonists SR144528 and AM630, but not CB2 agonist HU308 or CB1 antagonist SR141716, effectively inhibited IL-6-induced secretion of soluble IgM without affecting cell proliferation as measured by thymidine uptake. SR144528 alone had no effects on the basal levels of IgM in the resting cells. These effects were receptor mediated, as pretreatment with CB2 agonist abrogated SR144528-mediated inhibition of IL-6 stimulated IgM secretion. Transcription factors relevant to B cell differentiation, Bcl-6 and PAX5, as well as the protein kinase STAT3 pathway were involved in the inhibition of IL-6-induced IgM by SR144528. Conclusions These results uncover a novel function of CB2 antagonists and suggest that CB2 ligands may be potential modulators of immunoglobulin secretion. PMID:24913620

  4. Reinvestigating the Role of IgM in Rabies Virus Postexposure Vaccination

    PubMed Central

    Dorfmeier, Corin L.; Shen, Shixue; Tzvetkov, Evgeni P.

    2013-01-01

    B cells secreting IgG antibodies, but not IgM, are thought to be solely responsible for vaccine-induced protection against rabies virus (RABV) infections in postexposure settings. In this report, we reinvestigated the potential for IgM to mediate protection in a mouse model of RABV vaccination. Immunocompetent mice immunized with an experimental live replication-deficient RABV-based vaccine produced virus neutralizing antibodies (VNAs) within 3 days of vaccination. However, mice unable to produce soluble IgM (sIgM?/?) did not produce VNAs until 7 days postimmunization. Furthermore, sIgM?/? mice were not protected against RABV infection when challenged 3 days postimmunization, while all wild-type mice survived challenge. Consistent with the lack of protection against pathogenic RABV challenge, approximately 50- to 100-fold higher viral loads of challenge virus were detected in the muscle, spinal cord, and brain of immunized sIgM?/? mice compared to control mice. In addition, IgG antibody titers in vaccinated wild-type and sIgM?/? mice were similar at all time points postimmunization, suggesting that protection against RABV challenge is due to the direct effects of IgM and not the influence of IgM on the development of effective IgG antibody titers. In all, early vaccine-induced IgM can limit dissemination of pathogenic RABV to the central nervous system and mediate protection against pathogenic RABV challenge. Considering the importance for the rapid induction of VNAs to protect against RABV infections in postexposure prophylaxis settings, these findings may help guide the development of a single-dose human rabies vaccine. PMID:23760250

  5. Suppression of IgM Proteolysis by Conformational Stabilization Through Excipients

    PubMed Central

    Mueller, Monika; Loh, Maybelle Q. T.; Gagnon, Pete

    2015-01-01

    Protease activity from host cell lines may cause product loss or affect the quality of recombinant proteins. In this study, we showed that excipients like glycine and sorbitol reduce the proteolysis of an immunoglobulin M (IgM) in the presence of added proteases like ?-chymotrypsin, papain, and pepsin. The activity of the proteases in the IgM-protective environments was conserved or even enhanced as tested using low molecular weight substrates. Thus, a higher resistance against proteolytic degradation appears to be caused by the conformational stabilization of the IgM due to preferential exclusion of sorbitol and glycine. PMID:26839826

  6. IgM+ Memory B Cell Expression Predicts HIV-Associated Cryptococcosis Status

    PubMed Central

    Subramaniam, Krishanthi; Metzger, Brian; Hanau, Lawrence H.; Guh, Alice; Rucker, Lisa; Badri, Sheila; Pirofski, Liise-anne

    2009-01-01

    Background The role of B cells in resistance to Cryptococcus neoformans disease (i.e., cryptococcosis) is unknown. Given evidence that IgM+ memory B cells are required for immunity to other encapsulated pathogens, we hypothesized that these cells might contribute to resistance to cryptococcosis. Methods We compared levels of IgM expression on memory B cells in 29 HIV-infected individuals who had a history of cryptococcosis (the HIV+CN+ group) with levels in 30 human immunodeficiency virus (HIV)infected subjects who had no history of cryptococcosis (the HIV+CN? group) and 20 HIV-uninfected subjects who had no history of cryptococcosis (the HIV? group) (cohort 1). We also determined levels of IgM expression on memory B cells in banked samples obtained before cryptococcosis onset from 31 participants in the Multicenter AIDS Cohort Study, of whom 8 had HIV infection and subsequently developed cryptococcosis (the HIV+CN+ group), 8 had HIV infection and did not develop cryptococcosis (the HIV+CN? group), and 15 did not have HIV infection and did not develop cryptococcosis (the HIV? group) (cohort 2). Results In cohort 1, the percentage of memory B cells that expressed IgM was lower among HIV+CN+ subjects, compared with HIV+CN? subjects (P < .01) and HIV? subjects (P <.05); expression of IgM on ?50% of memory B cells was a significant predictor of C. neoformans disease status (odds ratio, 5.5; P = .03). In cohort 2, the percentage of memory B cells that expressed IgM was lower in HIV+CN+ subjects than in HIV+CN? subjects (P = .02) and HIV? subjects (P < .01); an IgM+ memory B cell percentage of ?38.5% was a significant predictor of future development of cryptococcosis (odds ratio, 14; P = .02). Conclusions These findings suggest that HIV-infected persons in whom the percentage of memory B cells that express IgM is decreased might be at greater risk for the development of cryptococcosis. PMID:19527168

  7. Spitzer Observations of Stephan's Quintet -- IGM Dust and Gas in a Multi-galaxy Collision

    NASA Astrophysics Data System (ADS)

    Xu, C. K.; Appleton, Ph.; Dopita, M.; Gao, Y.; Lu, N. Y.; Popescu, C.; Reach, W.; Tuffs, R.; Sulentic, J.; Yun, M.

    2005-12-01

    Stephan's Quintet (SQ) is the most famous and well studied compact group of galaxies. The rich literature archive of multi-wavelength data reveal one of the most fascinating pictures in the universe. We see a complex web of interactions between member galaxies and various constituents of the intragroup medium (IGM) which, in turn, have triggered spectacular activities such as a 40 kpc large scale shock and a strong IGM starburst. In this poster we will present our new Spitzer observations of SQ with unprecedented resolution and sensitivity. The observations impose new constraints on the physical conditions of the IGM gas and dust, the distribution and history of the star formation activity in member galaxies and in the IGM, as well as the effects of various interaction events that have occurred in the recent ( ˜ 1 Gyr) history of the group. Our results may have far-reaching inferences on studies of multi-nuclei ULIRGs and 'chain galaxies' found in high-z surveys. This work is based on observations made with the Spitzer Space Telescope, which is operated by the Jet Propulsion Laboratory, California Institute of Technology under a contract with NASA. Support for this work was provided by NASA through an award issued by JPL/Caltech

  8. Postsplenectomy cytomegaloviral mononucleosis: marked lymphocytosis, TCRgamma gene rearrangements, and impaired IgM response.

    PubMed

    Han, Xiang Y; Lin, Pei; Amin, Hesham M; Ferrajoli, Alessandra

    2005-04-01

    People who have undergone splenectomy mount a poor IgM response to bacterial polysaccharide vaccines. Whether this defect is true during natural bacterial and viral infections is unknown. We present 2 cases of postsplenectomy cytomegalovirus (CMV)-induced mononucleosis with impaired IgM but normal to augmented IgG response. The cases presented initial diagnostic challenges owing to a prolonged course of infection, marked lymphocytosis (peak lymphocyte count, 27,900/microL [27.9 10(9)/L]), clonal T-cell proliferation with T-cell receptor g gene rearrangements, and remote history of splenectomy. However, the acute nature of the infections, serial determinations of the anti-CMV IgM and IgG, exclusion of other causes, and detection of CMV in the blood established the diagnosis and revealed the deranged antibody response. The infections resolved without specific treatment. These cases suggest that the spleen might be a primary site for specific anti-CMV IgM response. PMID:15743745

  9. Atypical IgM multiple myeloma with deletion of c-MAF.

    PubMed

    Jurez Salcedo, L M; Lpez Rubio, M; Gil Fernndez, J J; Garcia-Suarez, J; Magro, E; Arranz, E; Gutirrez Jomarrn, I; Marcellini Antonio, S; Blasco, A; Burgaleta, C

    2015-10-01

    IgM multiple myeloma (MM) is a rare subtype of myeloma that shares clinical and pathological features with Waldenstrm's macroglobulinaemia. These are two separate entities that differ both in therapy and prognosis. We report a 57-year-old male, who presented with anaemia, hypercalcaemia, acute renal failure and several vertebral fractures that clinically suggested a multiple myeloma. Further investigations revealed a serum monoclonal component of IgM lambda type and a bone marrow infiltrated by small, lymphoplasmocytic cells. IgM MM was finally diagnosed by means of both inmunophenotypic and immunohistochemistry techniques, stressing the importance of inmunophenotypic evaluation when clinical and morphological features are discordant. Fluorescence in situ hybridization (FISH) studies disclosed a particular combination of deletion 13q14, t(11;14) and monoallelic deletion C-MAF without t(14;16). The clinical evolution after a Bortezomib-containing polychemotherapy and autologous stem cell transplantation (ASCT) conditioned with busulphan and melphalan is also presented. This very uncommon case highlights the impact of immunophenotyping on the differential diagnosis between IgM MM and WM, to choose the best treatment and establish an appropriate outcome. PMID:25996654

  10. [A case of selective IgM deficiency associated with systemic lupus erythematosus].

    PubMed

    Tanaka, A; Kasahara, M; Miyawaki, T; Yahata, K; Hashimoto, H; Sugawara, A; Ueda, S; Matsuo, T; Kuwahara, T

    1996-04-01

    We report a case of selective IgM deficiency associated with systemic lupus erythematosus (SLE). A 34-year-old female suffering from SLE was admitted with proteinuria and general fatigue. Laboratory findings revealed a very low serum IgM level, almost lower than 12 mg/dl. Renal biopsy findings showed diffuse proliferative lupus nephritis (DPLN). In immunofluorescent microscopy, IgG was the most strongly stained followed by IgA, but IgM staining was only faint. As for the immunophenotype of the T cells, the OKT4/OKT8 ratio was normal. Response to both phytohemagglutinin (PHA) and concanavalin A (ConA) was normal. However, responses of B cells to both pokeweed mitogen (PWM) and Staphylococcus aureus Cowan strain I (SAC) were significantly reduced. Surface IgM-positive B cells were decreased. These results indicate that the patient had B cell dysfunction, involving impairment of B cell differentiation. In this report, we discuss selective IgM deficiency and SLE documented in the literature. PMID:8709418

  11. Baryonic Content in the Warm-Hot IGM at Low Redshift

    NASA Technical Reports Server (NTRS)

    Sonneborn, George; Shull, M.; Danforth, C.; Moos, W.

    2007-01-01

    Baryons are 4.5% of the universe's mass/energy density; only 10% of these are in stars, galaxies, and clusters. At low-redshift 90% of baryons are in the IGM, 30% in Ly-alpha forest, but most are in hot gas (10(exp 5-7) K) produced by shocks during structure formation. O VI 1032-38 A are the best tracers of this gas. The distribution of O VI absorbers observed by FUSE rises as N(sup -2+/-0.2, down to 10(exp 13)/sq cm. Integrated to logN=13, 7% of baryons reside in the O VI-bearing IGM at 10% solar metallicity, T approx. 10(exp 5.5) K. At redshift z<0.1 metals have been transported less than 800/h kpc from L* galaxies and 200/h kpc from 0.1 L* galaxies. The steepness of dN/dz means that low-N absorbers contribute an equal mass of hot IGM as higher N gas. The total mass of O VI-bearing gas in the IGM depends on determining the turnover in dN/dz at low N(O VI). Future observations by FUSE are needed to reach lower N and to reduce the uncertainty in the dN/dz power law.

  12. Architecture of Human IgM in Complex with P. falciparum Erythrocyte Membrane Protein 1.

    PubMed

    Akhouri, Reetesh Raj; Goel, Suchi; Furusho, Hirotoshi; Skoglund, Ulf; Wahlgren, Mats

    2016-02-01

    Plasmodium falciparum virulence is associated with sequestration of infected erythrocytes. Microvascular binding mediated by PfEMP1 in complex with non-immune immunoglobulin M (IgM) is common among parasites that cause both severe childhood malaria and pregnancy-associated malaria. Here, we present cryo-molecular electron tomography structures of human IgM, PfEMP1 and their complex. Three-dimensional reconstructions of IgM reveal that it has a dome-like core, randomly oriented Fab2s units, and the overall shape of a turtle. PfEMP1 is a C- shaped molecule with a flexible N terminus followed by an arc-shaped backbone and a bulky C terminus that interacts with IgM. Our data demonstrate that the PfEMP1 binding pockets on IgM overlap with those of C1q, and the bulkiness of PfEMP1 limits the capacity of IgM to interact with PfEMP1. We suggest that P. falciparum exploits IgM to cluster PfEMP1 into an organized matrix to augment its affinity to host cell receptors. PMID:26776517

  13. Enzyme immunoassays for IgG and IgM antibodies to Toxoplasma gondii based on enhanced chemiluminescence.

    PubMed Central

    Crouch, C F

    1995-01-01

    AIMS--To evaluate the clinical performance of enzyme immunoassays for IgG and IgM antibodies to Toxoplasma gondii based on enhanced chemiluminescence. METHODS--Classification of routine clinical samples from the originating laboratories was compared with that obtained using the chemiluminescence based assays. Resolution of discordant results was achieved by testing in alternative enzyme immunoassays (IgM) or by an independent laboratory using the dye test (IgG). RESULTS--Compared with resolved data, the IgM assay was found to be highly specific (100%) with a cut off selected to give optimal performance with respect to both the early detection of specific IgM and the detection of persistent levels of specific IgM (sensitivity 98%). Compared with resolved data, the IgG assay was shown to have a sensitivity and a specificity of 99.4%. CONCLUSIONS--The Amerlite Toxo IgM assay possesses high levels of sensitivity and specificity. Assay interference due to rheumatoid factor like substances is not a problem. The Amerlite Toxo IgG assay possesses good sensitivity and specificity, but is less sensitive for the detection of seroconversion than methods detecting both IgG and IgM. PMID:7560174

  14. Inadequacy of IgM antibody tests for diagnosis of Rocky Mountain Spotted Fever.

    PubMed

    McQuiston, Jennifer H; Wiedeman, Caleb; Singleton, Joseph; Carpenter, L Rand; McElroy, Kristina; Mosites, Emily; Chung, Ida; Kato, Cecilia; Morris, Kevin; Moncayo, Abelardo C; Porter, Susan; Dunn, John

    2014-10-01

    Among 13 suspected Rocky Mountain spotted fever (RMSF) cases identified through an enhanced surveillance program in Tennessee, antibodies to Rickettsia rickettsii were detected in 10 (77%) patients using a standard indirect immunofluorescent antibody (IFA) assay. Immunoglobulin M (IgM) antibodies were observed for 6 of 13 patients (46%) without a corresponding development of IgG, and for 3 of 10 patients (30%) at least 1 year post-onset. However, recent infection with a spotted fever group rickettsiae could not be confirmed for any patient, based on a lack of rising antibody titers in properly timed acute and convalescent serologic specimens, and negative findings by polymerase chain reaction testing. Case definitions used in national surveillance programs lack specificity and may capture cases that do not represent current rickettsial infections. Use of IgM antibodies should be reconsidered as a basis for diagnosis and public health reporting of RMSF and other spotted fever group rickettsiae in the United States. PMID:25092818

  15. Evaluation of Three Commercially Available Japanese Encephalitis Virus IgM Enzyme-Linked Immunosorbent Assays

    PubMed Central

    Robinson, Jaimie S.; Featherstone, David; Vasanthapuram, Ravi; Biggerstaff, Brad J.; Desai, Anita; Ramamurty, Nalini; Chowdhury, Anwarul Haque; Sandhu, Hardeep S.; Cavallaro, Kathleen F.; Johnson, Barbara W.

    2010-01-01

    We evaluated performance of three commercial Japanese encephalitis virus (JEV) IgM antibody capture enzyme-linked immunosorbent assay (MAC ELISA) kits with a panel of serological specimens collected during a surveillance project of acute encephalitis syndrome in India and acute meningitis and encephalitis syndrome in Bangladesh. The serum and cerebral spinal fluid specimens had been referred to the Centers for Disease Control and Prevention (CDC) for confirmatory testing. The CDC results and specimen classifications were considered the reference standard. All three commercial kits had high specificity (9599.5%), but low sensitivities, ranging from 1757%, with both serum and cerebrospinal fluid samples. Specific factors contributing to low sensitivity compared with the CDC ELISA could not be determined through further analysis of the limits and dilution end points of IgM detection. PMID:21036854

  16. Antibodies to steroids from a small human naive IgM library.

    PubMed

    Dörsam, H; Rohrbach, P; Kürschner, T; Kipriyanov, S; Renner, S; Braunagel, M; Welschof, M; Little, M

    1997-09-01

    Human antibodies specific for digoxigenin, estradiol, testosterone and progesterone have been isolated from a small combinatorial IgM repertoire (4 x 10(7)) of single chain antibodies (scFv). The affinities of both the anti-estradiol and antiprogesterone scFv were approximately 10(8) M(-1). Naive IgM genes appeared to be highly represented, since only the heavy chain variable domain of the anti estradiol antibody contained differences to corresponding germline sequences. The light chain variable domain of the progesterone receptor was also identical to a germline sequence, showing that it is possible for completely naive antibodies to bind steroids with affinities comparable to those obtained after a secondary immune response. PMID:9305722

  17. The Evolution of Multiple Isotypic IgM Heavy Chain Genes in the Shark1

    PubMed Central

    Lee, Victor; Huang, Jing Li; Lui, Ming Fai; Malecek, Karolina; Ohta, Yuko; Mooers, Arne; Hsu, Ellen

    2008-01-01

    The IgM H chain gene organization of cartilaginous fishes consists of 15200 miniloci, each with a few gene segments (VH-D1-D2-JH) and one C gene. This is a gene arrangement ancestral to the complex IgH locus that exists in all other vertebrate classes. To understand the molecular evolution of this system, we studied the nurse shark, which has relatively fewer loci, and characterized the IgH isotypes for organization, functionality, and the somatic diversification mechanisms that act upon them. Gene numbers differ slightly between individuals (~15), but five active IgM subclasses are always present. Each gene undergoes rearrangement that is strictly confined within the minilocus; in B cells there is no interaction between adjacent loci located ?120 kb apart. Without combinatorial events, the shark IgM H chain repertoire is based on junctional diversity and, subsequently, somatic hypermutation. We suggest that the significant contribution by junctional diversification reflects the selected novelty introduced by RAG in the early vertebrate ancestor, whereas combinatorial diversity coevolved with the complex translocon organization. Moreover, unlike other cartilaginous fishes, there are no germline-joined VDJ at any nurse shark ? locus, and we suggest that such genes, when functional, are species-specific and may have specialized roles. With an entire complement of IgM genes available for the first time, phylogenetic analyses were performed to examine how the multiple Ig loci evolved. We found that all domains changed at comparable rates, but VH appears to be under strong positive selection for increased amino acid sequence diversity, and surprisingly, so does C?2. PMID:18490746

  18. Comparison of chemiluminescent immunoassay and ELISA for measles IgG and IgM.

    PubMed

    de Ory, Fernando; Minguito, Teodora; Balfagón, Pilar; Sanz, Juan C

    2015-08-01

    In the context of measles elimination, the identification of recent infections is important for clinical laboratories. Serological diagnosis is achieved by detecting specific IgG and IgM. Recently an automated chemiluminescent immunoassay (CLIA) (Liaison, DiaSorin, Italy) has been used to quantify the measles antibody. The aim of this study was to compare this assay with Enzygnost ELISA (Siemens, Germany), with final classification of discrepancies by indirect immunofluorescence (Euroimmun, Germany). For measles IgM, 204 sera were analyzed: 50 IgM-positive, 104 IgM-negative/IgG-positive, and 50 from other viral infections (B19V, rubella, mumps, CMV, and EBV). For the measles IgG assay, 162 samples were tested: 106 were positive and 56 were negative. For measles IgM, the sensitivity and specificity of CLIA against ELISA were 94% (95% CI: 83.2-98.6) and 100% (95% CI: 97.1-100), respectively; the corrected figures after the final classification of discrepancies were 100% (95% CI: 91.0-100) and 99.4% (95% CI: 96.1-100), respectively. In relation to IgG, the sensitivity and specificity of CLIA against ELISA were, respectively, 97.2% (95% CI: 91.7-99.4) and 92.9% (95% CI: 82.5-97.7), and 95.5% (95% CI: 89.5-98.3) and 100% (95% CI: 91.8-100) after the final classification. CLIA showed excellent sensitivity and specificity in detecting measles IgG and IgM antibodies, eliminating the need to aliquot specimens before carrying out the assay. PMID:26140432

  19. Serum Free Light Chain Only Myeloma with Cytoplasmic IgM.

    PubMed

    Ebana, Hideaki; Nakamura, Ken-Ichi; Nozawa, Yoshihiro; Seki, Ritsuko; Mita, Masayuki

    2014-01-01

    In the past decade, the serum free light chain (FLC) immunoassays have become widely available enabling greater sensitivity in the diagnosis and management of monoclonal light chain diseases. Here, we describe a rare case of serum free light chain only myeloma with cytoplasmic IgM. A 75-year-old woman presented with a progressively worsening lumbosacral pain. FDG PET/CT images showed increased FDG uptake in the sacral mass, vertebral bodies, and ribs. Laboratory data found hypogammaglobulinemia and the bone marrow aspirate revealed only 2.2% of plasma cells. The serum and urine protein electrophoresis did not detect a monoclonal band. However, the serum FLC immunoassays reported an abnormal kappa/lambda ratio (0.001) indicating the presence of monoclonal lambda FLC. The sacral tumor biopsy revealed proliferation of plasma cells and immunohistochemical staining showed that the plasma cells were positive for CD138, IgM, and lambda light chain but negative for CD20. This case may have previously been described as a nonsecretory IgM myeloma but recently would be identified as free light chain only myeloma. The immunohistochemical and genetic features of the clonal plasma cells in free light chain only myeloma need to be further investigated to better understand the relevance and incidence of this myeloma type. PMID:25028614

  20. A patterned recombinant human IgM guides neurite outgrowth of CNS neurons

    PubMed Central

    Xu, Xiaohua; Wittenberg, Nathan J.; Jordan, Luke R.; Kumar, Shailabh; Watzlawik, Jens O.; Warrington, Arthur E.; Oh, Sang-Hyun; Rodriguez, Moses

    2013-01-01

    Matrix molecules convey biochemical and physical guiding signals to neurons in the central nervous system (CNS) and shape the trajectory of neuronal fibers that constitute neural networks. We have developed recombinant human IgMs that bind to epitopes on neural cells, with the aim of treating neurological diseases. Here we test the hypothesis that recombinant human IgMs (rHIgM) can guide neurite outgrowth of CNS neurons. Microcontact printing was employed to pattern rHIgM12 and rHIgM22, antibodies that were bioengineered to have variable regions capable of binding to neurons or oligodendrocytes, respectively. rHIgM12 promoted neuronal attachment and guided outgrowth of neurites from hippocampal neurons. Processes from spinal neurons followed grid patterns of rHIgM12 and formed a physical network. Comparison between rHIgM12 and rHIgM22 suggested the biochemistry that facilitates anchoring the neuronal surfaces is a prerequisite for the function of IgM, and spatial properties cooperate in guiding the assembly of neuronal networks. PMID:23881231

  1. The importance of IgM positivity in laboratory diagnosis of gestational and congenital syphilis.

    PubMed

    Nemes-Nikodém, E; Vörös, E; Pónyai, K; Párducz, L; Kárpáti, S; Rozgonyi, F; Ostorházi, E

    2012-06-01

    From January 1, 2009 through December 31, 2011, from 33,753 blood samples for syphilis screening, Treponema pallidum infections were confirmed in 241 pregnant women at the Department of Dermatology, Venerology, and Dermatooncology of Semmelweis University Budapest. In this period, four children born to inadequately or untreated women were confirmed to have connatal syphilis. The height of rapid plasma reagin (RPR) titer was measured to determine the stage of the infection and to examine the success of the antilues therapy. The diagnosis of maternal syphilis infection was confirmed with enzyme linked immunosorbent assay (ELISA), T. pallidum particle agglutination (TPPA), and IgG and IgM immunoblots. Maternal IgM immunoblot results identify mothers at risk of delivering babies with connatal syphilis better than the height of maternal RPR titer. The standard serological tests are less useful in newborns because of IgG transfer across the placenta. IgM test which depends on the infant's response has more specificity in diagnosing connatal syphilis. PMID:24672684

  2. A patterned recombinant human IgM guides neurite outgrowth of CNS neurons

    NASA Astrophysics Data System (ADS)

    Xu, Xiaohua; Wittenberg, Nathan J.; Jordan, Luke R.; Kumar, Shailabh; Watzlawik, Jens O.; Warrington, Arthur E.; Oh, Sang-Hyun; Rodriguez, Moses

    2013-07-01

    Matrix molecules convey biochemical and physical guiding signals to neurons in the central nervous system (CNS) and shape the trajectory of neuronal fibers that constitute neural networks. We have developed recombinant human IgMs that bind to epitopes on neural cells, with the aim of treating neurological diseases. Here we test the hypothesis that recombinant human IgMs (rHIgM) can guide neurite outgrowth of CNS neurons. Microcontact printing was employed to pattern rHIgM12 and rHIgM22, antibodies that were bioengineered to have variable regions capable of binding to neurons or oligodendrocytes, respectively. rHIgM12 promoted neuronal attachment and guided outgrowth of neurites from hippocampal neurons. Processes from spinal neurons followed grid patterns of rHIgM12 and formed a physical network. Comparison between rHIgM12 and rHIgM22 suggested the biochemistry that facilitates anchoring the neuronal surfaces is a prerequisite for the function of IgM, and spatial properties cooperate in guiding the assembly of neuronal networks.

  3. Purification of the Sm nuclear autoantigen. Detection and clinical significance of IgM antibody.

    PubMed Central

    Pollard, K M; Tan, E M

    1985-01-01

    Sm antigen from rabbit thymus acetone powder was purified using a combination of ammonium sulphate precipitation, DEAE-Sephacel and hydroxyapatite chromatography. This preparation was devoid of previously identified nuclear antigens including ribonucleoprotein (U1-RNP), proliferating cell nuclear antigen (PCNA), Sjgren's syndrome antigen A (SS-A/Ro), Sjgren's syndrome antigen B (SS-B/La), Sjgren's lupus antigen (SL), scleroderma antigen 70 (Scl-70), DNA and histones. The purified material was used in an enzyme linked immunosorbent assay (ELISA) to detect anti-Sm antibody. All sera with precipitating Sm antibody detected by immunodiffusion gave reactions in ELISA greater than 0.40 OD405 and contained predominantly IgG anti-Sm antibody. Of 112 sera which did not have anti-Sm by immunodiffusion there were five which gave reactions greater than 0.40 OD405. Four of these five sera contained only IgM antibody and the fifth contained both IgM and IgG. Of these five, one came from a 'normal' control who had a positive anti-nuclear antibody (ANA), facial rash and diabetes, two were from patients with systemic lupus erythematosus (SLE) and two were from patients with mixed connective tissue disease (MCTD). These findings demonstrate that there are patients whose anti-Sm response may be restricted to IgM and in some of these patients the clinical presentation may be different from that of classical SLE. PMID:4017287

  4. Nomenclature of Toso, Fas apoptosis inhibitory molecule 3, and IgM FcR.

    PubMed

    Kubagawa, Hiromi; Carroll, Michael C; Jacob, Chaim O; Lang, Karl S; Lee, Kyeong-Hee; Mak, Tak; McAndrews, Monica; Morse, Herbert C; Nolan, Garry P; Ohno, Hiroshi; Richter, Günther H; Seal, Ruth; Wang, Ji-Yang; Wiestner, Adrian; Coligan, John E

    2015-05-01

    Hiromi Kubagawa and John E. Coligan coordinated an online meeting to define an appropriate nomenclature for the cell surface glycoprotein presently designated by different names: Toso, Fas apoptosis inhibitory molecule 3 (FAIM3), and IgM FcR (FcμR). FAIM3 and Faim3 are the currently approved symbols for the human and mouse genes, respectively, in the National Center for Biotechnology Information, Ensembl, and other databases. However, recent functional results reported by several groups of investigators strongly support a recommendation for renaming FAIM3/Faim3 as FCMR/Fcmr, a name better reflecting its physiological function as the FcR for IgM. Participants included 12 investigators involved in studying Toso/FAIM3(Faim3)/FμR, representatives from the Human Genome Nomenclature Committee (Ruth Seal) and the Mouse Genome Nomenclature Committee (Monica McAndrews), and an observer from the IgM research field (Michael Carroll). In this article, we provide a brief background of the key research on the Toso/FAIM3(Faim3)/FcμR proteins, focusing on the ligand specificity and functional activity, followed by a brief summary of discussion about adopting a single name for this molecule and its gene and a resulting recommendation for genome nomenclature committees. PMID:25888699

  5. Comparative biochemical characterization of a human IgM produced in both ascites and in vitro cell culture

    SciTech Connect

    Monica, T.J.; Goochee, C.F.; Maiorella, B.L. )

    1993-04-01

    Researchers have conducted a comparative analysis of a monoclonal human IgM obtained from cells cultured in nude-mouse ascites and from the same cells cultured in a bioreactor. We studied the glycosylation of the IgMs using lectin blotting and high-pH anion-exchange chromatography with pulsed amperometric detection (HPAE-PAD), and we also developed reverse phase liquid chromatography (RPLC) peptide maps of the IgM samples. The HPAE-PAD data indicate that the samples differ in both the type and distribution of oligosaccharides present on the IgMs. In addition, the proteins differ in their solubility behavior and in their RPLC peptide maps. We conclude that the method of cell culture of capable of significantly altering the characteristics of the glycoprotein product. 27 refs., 5 figs.

  6. Pathogenic Relevance of IgG and IgM Antibodies against Desmoglein 3 in Blister Formation in Pemphigus Vulgaris

    PubMed Central

    Tsunoda, Kazuyuki; Ota, Takayuki; Saito, Masataka; Hata, Tsuyoshi; Shimizu, Atsushi; Ishiko, Akira; Yamada, Taketo; Nakagawa, Taneaki; Kowalczyk, Andrew P.; Amagai, Masayuki

    2011-01-01

    Pemphigus vulgaris is an autoimmune disease caused by IgG antibodies against desmoglein 3 (Dsg3). Previously, we isolated a pathogenic mAb against Dsg3, AK23 IgG, which induces a pemphigus vulgaris-like phenotype characterized by blister formation. In the present study, we generated a transgenic mouse expressing AK23 IgM to examine B-cell tolerance and the pathogenic role of IgM. Autoreactive transgenic B cells were found in the spleen and lymph nodes, whereas anti-Dsg3 AK23 IgM was detected in the cardiovascular circulation. The transgenic mice did not develop an obvious pemphigus vulgaris phenotype, however, even though an excess of AK23 IgM was passively transferred to neonatal mice. Similarly, when hybridoma cells producing AK23 IgM were inoculated into adult mice, no blistering was observed. Immunoelectron microscopy revealed IgM binding at the edges of desmosomes or interdesmosomal cell membranes, but not in the desmosome core, where AK23 IgG binding has been frequently detected. Furthermore, in an in vitro dissociation assay using cultured keratinocytes, AK23 IgG and AK23 IgM F(ab?)2 fragments, but not AK23 IgM, induced fragmentation of epidermal sheets. Together, these observations indicate that antibodies must gain access to Dsg3 integrated within desmosomes to induce the loss of keratinocyte cell-cell adhesion. These findings provide an important framework for improved understanding of B-cell tolerance and the pathophysiology of blister formation in pemphigus. PMID:21718682

  7. Biotin IgM Antibodies in Human Blood: A Previously Unknown Factor Eliciting False Results in Biotinylation-Based Immunoassays

    PubMed Central

    Chen, Tingting; Hedman, Lea; Mattila, Petri S.; Jartti, Laura; Jartti, Tuomas; Ruuskanen, Olli; Sderlund-Venermo, Maria; Hedman, Klaus

    2012-01-01

    Biotin is an essential vitamin that binds streptavidin or avidin with high affinity and specificity. As biotin is a small molecule that can be linked to proteins without affecting their biological activity, biotinylation is applied widely in biochemical assays. In our laboratory, IgM enzyme immuno assays (EIAs) of -capture format have been set up against many viruses, using as antigen biotinylated virus like particles (VLPs) detected by horseradish peroxidase-conjugated streptavidin. We recently encountered one serum sample reacting with the biotinylated VLP but not with the unbiotinylated one, suggesting in human sera the occurrence of biotin-reactive antibodies. In the present study, we search the general population (612 serum samples from adults and 678 from children) for IgM antibodies reactive with biotin and develop an indirect EIA for quantification of their levels and assessment of their seroprevalence. These IgM antibodies were present in 3% adults regardless of age, but were rarely found in children. The adverse effects of the biotin IgM on biotinylation-based immunoassays were assessed, including four inhouse and one commercial virus IgM EIAs, showing that biotin IgM do cause false positivities. The biotin can not bind IgM and streptavidin or avidin simultaneously, suggesting that these biotin-interactive compounds compete for the common binding site. In competitive inhibition assays, the affinities of biotin IgM antibodies ranged from 2.110?3 to 1.710?4 mol/L. This is the first report on biotin antibodies found in humans, providing new information on biotinylation-based immunoassays as well as new insights into the biomedical effects of vitamins. PMID:22879954

  8. [IgM in the diagnosis of syphilis: results on the use of the IgM solid-phase hemadsorption test].

    PubMed

    Panuccio, A; Gelosa, L

    1985-01-01

    IgM-SPHA test was improved for IgM treponema-specific determination. The test can find routinary application because it does not require for its execution special equipments, and is very easy. With this test 160 sera of luetic subjects were examined 103 were treated and 57 were affected by lues at different stages and untreated. The test is rather sensitive in the secondary and latent lues and in the reinfections, while the results are paradoxically less satisfactory in the primary syphilis. The test can be a precious diagnostic tool since, beside allowing to decide the recovery from the disease from an immunological point, finds further applications in the connatal and neurological lues. PMID:4091975

  9. Natural IgM is Produced by CD5− Plasma Cells that Occupy a Distinct Survival Niche in Bone Marrow

    PubMed Central

    Reynolds, Alexander E.; Kuraoka, Masayuki; Kelsoe, Garnett

    2014-01-01

    Natural IgM is constitutively present in the serum, where it aids in the early control of viral and bacterial expansion. Natural IgM also plays a significant role in the prevention of autoimmune disease by promoting the clearance of cellular debris. Nevertheless, the origins of natural IgM have not been precisely defined. Previous studies have focused on the role of CD5+ B1 cells in the production of natural IgM, but we show here that a discrete population of CD5− IgM plasmablasts and plasma cells in the BM produces the majority of serum IgM in resting mice. These ASC originate from peritoneal cavity-resident cells, as transfer of peritoneal cells completely restores serum IgM and the specific compartment of BM ASC in Rag1-deficient mice. We show that BM natural IgM ASC arise from a fetal-lineage progenitor that is neither B1a nor B1b, and that this IgM ASC compartment contains a substantial fraction of long-lived plasma cells that do not occupy the IgG plasma cell survival niche in the BM, but are instead supported by IL-5. In summary, we have identified the primary source of natural IgM, and shown that these ASC are maintained long-term in a unique survival niche within the BM. PMID:25429072

  10. HOW TO SEARCH FOR ISLANDS OF NEUTRAL HYDROGEN IN THE z ∼ 5.5 IGM

    SciTech Connect

    Malloy, Matthew; Lidz, Adam

    2015-02-01

    Observations of the Lyman-alpha (Lyα) forest may allow reionization to complete as late as z ∼ 5.5, provided the ionization state of the intergalactic medium (IGM) is sufficiently inhomogeneous at these redshifts. In this case, significantly neutral islands may remain among highly ionized gas with the ionized regions allowing some transmission through the Lyα forest. This possibility has the important virtue that it is eminently testable with existing Lyα forest data. In particular, we describe three observable signatures of significantly neutral gas in the z ∼ 5.5 IGM. We use mock quasar spectra produced from numerical simulations of reionization to develop these tests. First, we quantify how the abundance and length of absorbed regions in the forest increase with the volume-averaged neutral fraction in our reionization model. Second, we consider stacking the transmission profile around highly absorbed regions in the forest. If and only if there is significantly neutral gas in the IGM, absorption in the damping wing of the Lyα line will cause the transmission to recover slowly as one moves from absorbed to transmitted portions of the spectrum. Third, the deuterium Lyβ line should imprint a small but distinctive absorption feature slightly blueward of absorbed neutral regions in the Lyβ forest. We show that these tests can be carried out with existing Keck HIRES spectra at z ∼ 5.5, with the damping wing being observable for 〈x{sub H} {sub I}〉≳0.05 and the deuterium feature observable with additional high-resolution spectra for 〈x{sub H} {sub I}〉≳0.2.

  11. IgG and IgM autoantibody differences in discoid and systemic lupus patients

    PubMed Central

    Chong, Benjamin F.; Tseng, Lin-chiang; Lee, Thomas; Vasquez, Rebecca; Li, Quan Z.; Zhang, Song; Karp, David R.; Olsen, Nancy J.; Mohan, Chandra

    2012-01-01

    Systemic lupus (SLE) patients with discoid lupus (DLE) were reported to have milder disease. To test this observation, we employed sandwich arrays containing 98 autoantigens to compare autoantibody profiles of SLE subjects without DLE (DLE?SLE+) (N=9), SLE subjects with DLE (DLE+SLE+) (N=10), DLE subjects without SLE (DLE+SLE?) (N=11), and healthy controls (N=11). We validated differentially expressed autoantibodies using immunoassays in DLE?SLE+ (N=18), DLE+SLE+ (N=17), DLE+SLE? (N=23), and healthy subjects (N=22). Arrays showed 15 IgG autoantibodies (ten against nuclear antigens) and four IgM autoantibodies that were differentially expressed (q-value<0.05). DLE?SLE+ subjects had higher IgG autoantibodies against dsDNA, ssDNA, dsRNA, histone H2A and H2B, and SS-A (52 kDa) than all other groups including DLE+SLE+ subjects (p<0.05). Immunoassays measuring anti-dsDNA, -ssDNA, and -SS-A (52 kDa) IgG autoantibodies showed similar trends (p<0.05). Healthy and DLE+SLE?subjects expressed higher IgM autoantibodies against alpha beta crystallin, lipopolysaccharide, heat shock cognate 70, and desmoglein-3 than DLE+SLE+ and DLE?SLE+ subjects. IgG:IgM ratios of autoantibodies against nuclear antigens progressively rose from healthy to DLE?SLE+ subjects. In conclusion, lower IgG autoantibodies against nuclear antigens in DLE+SLE+ versus DLE?SLE+ subjects suggest that DLE indicates lower disease severity. Higher IgM autoantibodies against selected antigens in healthy and DLE+SLE?subjects may be non-pathogenic. PMID:22763789

  12. [Frequency of ABO type IgM antibody in 276 infants younger than six months].

    PubMed

    Ma, Shu-Xuan; Xu, Xi-Wei; Song, Wen-Qi; Shao, Hua; Xue, Hui; Zhang, Qing-Xiu

    2008-08-01

    The aim of study was to explore the frequency of ABO type IgM antibody in infants younger than six months. 309 hospitalized infants younger than six months were selected at first and their EDTA K(3) anticoagulant blood samples were taken. All the infants were divided into five groups: neonates within 1 week as group I; neonates aged 8 to 14 days as group II; neonates aged 15 days to 1 month as group III; infants aged two to 3 months as group IV and infants aged 4 to 6 months as group V. The monocolonal anti-A, anti-B serums, A cells, B cells and O cells were utilized to carried out the blood typing with tube test. The results indicated that from 309 samples tested 33 AB type sample were excluded. Out of the remains of 276 samples, 29 of 46 samples in group I were positive and with the ABO type consistent rate 63% (29/46); 41 of 64 samples in group II were positive and with the ABO type consistent rate 64% (41/64); 47 of 74 samples in group III were positive and with the ABO type consistent rate 63% (47/74); 28 of 45 samples in group IV were positive and with the ABO type consistent rate 62% (28/45); 40 of 47 samples in group V were positive and with the ABO type consistent rate 85%. It is concluded that the ABO type IgM antibody appear in most infants younger than six months and these IgM antibodies may be regarded as the important evidence for ABO typing in infants. PMID:18718090

  13. Production and characterization of monoclonal antibodies to IgM of Pacific herring (Clupea pallasii)

    USGS Publications Warehouse

    Purcell, Maureen K.; Bromage, Erin S.; Silva, Jessica; Hansen, John D.; Badil, Samantha M.; Woodson, James C.; Hershberger, Paul K.

    2012-01-01

    Pacific herring (Clupea pallasii) have a central role in the North Pacific ecosystem as a forage fish species and are natural reservoirs of several important finfish pathogens, including Viral hemorrhagic septicemia virus (VHSV). Here, we report the identification of the gene encoding the immunoglobulin mu (IgM) heavy chain, as well as the development and characterization of monoclonal antibodies (MAbs) that specifically react with Pacific herring IgM. Pacific herring immunoglobulin was purified and consisted of heavy and light chains of approximately 80 and 25 kDa. Three hybridoma clones were initially identified by ELISA as reactive with purified immunoglobulin but only one clone was able to detect an 80 kDa protein in Pacific and Atlantic herring (Clupea harengus) whole plasma by denaturing western blot. However, all three MAbs were able to precipitate an 80 kDa protein from Pacific herring and LCMS sequencing of peptide fragments derived from this protein matched the predicted amino acid sequence of the cloned, heavy chain gene. In addition, two of the MAbs stained cells within the putative lymphocyte gates for the spleen, anterior kidney and posterior kidney but were not reactive for myeloid/granulocyte gates, which is consistent with these MAbs reacting with surface IgM+ B-cells. To our knowledge, this is the first report of IgM-related gene sequences and anti-IgM monoclonal antibodies from any member of the family Clupeidae. The antibodies produced in this study are critical for achieving our long-term goal of conducting serological surveillance to assess pathogen exposure in natural populations of Pacific herring.

  14. Rapid immunoenzymatic technique for titration of rabies antibodies IgG and IgM.

    PubMed

    Savy, V; Atanasiu, P

    1978-01-01

    This report is concerned with the application of the enzyme immunoassay to measure the antibodies in humans vaccinated against rabies or presenting symptoms of rabies without having been vaccinated. By the same technique we identify the IgG and IgM classes of antibodies. The antigen (5 microgram/ml), purified virus, is readily adsorbed into polystyrene tube by passive adsorption. The use of only one dilution for each serum assay (1/200) is particularly suitable for epidemiological studies. Antibody response of subjects in the course of rabies vaccination was an obvious application. After 5 inoculations of tissue culture vaccine the IgM response was poor and late; it was even negative in two cases. The IgG response appeared early on the 7th day. In the same way we tried to follow antibody response in three cases of rabies in man. Seroneutralisation (SN) antibody were not detected at the beginning of the illness. In case 1 antibodies were found on the 12th day, in case 2 on the 7th day and in case 3 on the 8th day. When we assayed the serum samples for immunoenzymatic test, we found that the sera became positive some days earlier: on the 5th for case 1, already on the 1st day for the two others. In each of these three cases the positivity of the test corresponded to the presence of IgM class globulins since IgG detection remained negative as did the SN test. Our results could have some clinical interest concerning future rabies treatment and early diagnosis. PMID:355018

  15. Murine Visceral Leishmaniasis: IgM and Polyclonal B-Cell Activation Lead to Disease Exacerbation

    PubMed Central

    Deak, Eszter; Jayakumar, Asha; Wing Cho, Ka; Goldsmith-Pestana, Karen; Dondji, Blaise; Lambris, John D.; McMahon-Pratt, Diane

    2010-01-01

    In visceral leishmaniasis, the draining lymph node (DLN) is the initial site for colonization and establishment of infection after intradermal transmission by the sand fly vector; however, little is known about the developing immune response within this site. Using an intradermal infection model, which allows for parasite visceralization, we have examined the ongoing immune responses in the DLN of BALB/c mice infected with L. infantum. Although not unexpected, at early times post-infection there is a marked B cell expansion in the DLN, which persists throughout infection. However, the characteristics of this response were of interest; as early as day 7 post-infection, polyclonal antibodies (TNP, OVA, chromatin) were observed and the levels appeared comparable to the specific anti-leishmania response. Although B-cell-deficient JHD BALB/c mice are relatively resistant to infection, neither B-cell-derived IL-10 nor B-cell antigen presentation appear to be primarily responsible for the elevated parasitemia. However, passive transfer and reconstitution of JHD BALB/c with secretory immunoglobulins, (IgM or IgG; specific or non-specific immune complexes) results in increased susceptibility to L. infantum infection. Further, JHD BALB/c mice transgenetically reconstituted to secrete IgM demonstrated exacerbated disease in comparison to wild type BALB/c mice as early as 2 days post-infection. Evidence suggests that complement activation (generation of C5a) and signaling via the C5aR (CD88) is related to the disease exacerbation caused by IgM rather than cytokine levels (IL-10 or IFN-?). Overall these studies indicate that polyclonal B cell activation, which is known to be associated with human visceral leishmaniasis, is an early and intrinsic characteristic of disease and may represent a target for therapeutic intervention. PMID:20213734

  16. Carbohydrate specificity of IgM autoantibodies to CD45 in systemic lupus erythematosus.

    PubMed

    Fernsten, P D; Czyzyk, J K; Mimura, T; Winfield, J B

    1994-01-01

    Patients with SLE develop IgM autoantibodies to different isoforms of CD45, the major surface membrane protein tyrosine phosphatase on lymphocytes and other nucleated hemopoietic cells. Because such autoantibodies could have a potential role in the development of immune dysfunction in this disorder, we performed a series of experiments to characterize their antigenic specificity further. Blots of recombinant E. coli fusion proteins encoded by exons 3-7 of the p220 and p180 isoforms were uniformly non-reactive with SLE IgM, suggesting that anti-CD45 autoantibodies in SLE are directed against conformational and/or carbohydrate epitopes, rather than linear polypeptide epitopes. This issue was examined further using chemically and enzymatically modified CD45 purified from T cells by lectin affinity chromatography as substrates. Treatment of CD45 with 25 mM sodium-m-periodate, sufficient to abrogate binding to various lectins, abolished the reactivity with SLE anti-CD45 autoantibodies. On the other hand, digestion of CD45 with neuraminidase enhanced the binding of anti-CD45 autoantibodies from some of the SLE sera. This result probably reflects decreased steric hindrance or charge repulsion because the binding of mouse monoclonal antibodies directed against linear polypeptide epitopes of CD45 was similarly enhanced. Digestion of CD45 with N-glycosidase F had no effect on autoantibody staining. Taken together, these data suggest that IgM anti-CD45 autoantibodies in SLE recognize non-sialylated carbohydrate determinants in the highly O-glycosylated polymorphic domains of CD45. PMID:7536298

  17. Immune Deficiency State in a Girl with Eczema and Low Serum IgM

    PubMed Central

    Evans, D. I. K.; Holzel, A.

    1970-01-01

    This report concerns an immune deficiency disorder in a girl with eczema. She has had recurrent infections including three severe attacks of herpes simplex and five attacks of pneumococcal meningitis. There is a moderate lymphopenia, dysgammaglobulinaemia with high IgG, high IgA, and low IgM; lymphocyte transformation with phytohaemagglutinin is impaired. Production of circulating antibody is abnormal, as are delayed hypersensitivity reactions. Although there is no thrombocytopenia, the resemblance to the Wiskott-Aldrich syndrome is discussed. ImagesFIG. 1.FIG. 2.FIG. 3 PMID:5506938

  18. Association between IgM Anti-Herpes Simplex Virus and Plasma Amyloid-Beta Levels

    PubMed Central

    Fart, Catherine; Helmer, Catherine; Fleury, Herv; Bjot, Yannick; Ritchie, Karen; Amouyel, Philippe; Schraen-Maschke, Susanna; Bue, Luc; Lambert, Jean-Charles; Letenneur, Luc; Dartigues, Jean-Franois

    2011-01-01

    Objective Herpes simplex virus (HSV) reactivation has been identified as a possible risk factor for Alzheimer's disease (AD) and plasma amyloid-beta (A?) levels might be considered as possible biomarkers of the risk of AD. The aim of our study was to investigate the association between anti-HSV antibodies and plasma A? levels. Methods The study sample consisted of 1222 subjects (73.9 y in mean) from the Three-City cohort. IgM and IgG anti-HSV antibodies were quantified using an ELISA kit, and plasma levels of A?140 and A?142 were measured using an xMAP-based assay technology. Cross-sectional analyses of the associations between anti-HSV antibodies and plasma A? levels were performed by multi-linear regression. Results After adjustment for study center, age, sex, education, and apolipoprotein E-e4 polymorphism, plasma A?142 and A?140 levels were specifically inversely associated with anti-HSV IgM levels (??=??20.7, P?=?0.001 and ??=??92.4, P?=?0.007, respectively). In a sub-sample with information on CLU- and CR1-linked SNPs genotyping (n?=?754), additional adjustment for CR1 or CLU markers did not modify these associations (adjustment for CR1 rs6656401, ??=??25.6, P?=?0.002 for A?142 and ??=??132.7, P?=?0.002 for A?140; adjustment for CLU rs2279590, ??=??25.6, P?=?0.002 for A?142 and ??=??134.8, P?=?0.002 for A?140). No association between the plasma A?142-to-A?140 ratio and anti-HSV IgM or IgG were evidenced. Conclusion High anti-HSV IgM levels, markers of HSV reactivation, are associated with lower plasma A?140 and A?142 levels, which suggest a possible involvement of the virus in the alterations of the APP processing and potentially in the pathogenesis of AD in human. PMID:22216291

  19. Selective IgM deficiency in an adult presenting with Streptococcus pneumoniae septic arthritis.

    PubMed

    Phuphuakrat, Angsana; Ngamjanyaporn, Pintip; Nantiruj, Kanokrat; Luangwedchakarn, Voravich; Malathum, Kumthorn

    2016-02-01

    Septic arthritis caused by Streptococcus pneumoniae is uncommon. Most of the patients who have invasive pneumococcal infection have underlying diseases associated with impaired immune function. We report a case of polyarticular pneumococcal septic arthritis in a previously healthy adult as the first manifestation of selective immunoglobulin (Ig)M deficiency. The patient had no evidence of autoimmune disease or malignancy. Serum IgG, IgA, and complement levels were normal. Numbers of lymphocyte subsets were in normal range except that of CD4+ cells, which was slightly low. Invasive pneumococcal disease in a healthy adult should lead to further investigation for underlying diseases including primary immunodeficiencies. PMID:23523054

  20. [Utility and limitation of the rapid IgM antibody detection test for the diagnosis of Mycoplasma pneumoniae infection].

    PubMed

    Narita, Mitsuo

    2007-03-01

    I evaluated performance of the Mycoplasma pneumoniae-specific IgM antibody rapid detection test (ImmunoCard Mycoplasma, IC, Meridian, USA) and compared it to the particle agglutination (PA) test and ELISA tests (Mycoplasma pneumoniae IgG, IgA, IgM ELISA medac, Medac Diagnostika, Germany). Serum samples numbering 112 were obtained from 70 pediatric patients (< 16 years old) with M. pneumoniae infection diagnosed by a PA test (four-fold or greater rise by paired serum samples or > or = 1:640 by a single serum sample). Of these, 82 samples (73.2%) were positive in IC and 91 (81.3%) positive in ELISA IgM tests. Specifically, for samples obtained within 7 days following the onset of fever, 6 of the 14 positive in the ELISA IgM test were negative in IC and 4 of the 18 samples negative in the ELISA IgM test were positive in IC. I ascribed this difference to the difference in antigens used in each test. In the analysis of sequential serum samples from 2 patients with M. pneumoniae pneumonia, IC was still positive in 248- and 527-day samples for which a PA test and the ELISA IgM and IgG tests indicated no acute infection. Nine (36.0%) of 25 serum samples obtained from apparently healthy adult volunteers were positive in IC. Of the 9 IC-positive cases, ELISA tests suggested possible recent infection at most in 3 cases, while the remaining 6 cases had no evidence of acute infection. In conclusion, although IC is sufficiently sensitive as a rapid screening test for detecting M. pneumoniae-specific IgM antibody, a positive result in the test does not always indicate acute infection by this organism. To ensure accurate diagnosis of M. pneumoniae infection, paired serum samples are thus required for conventional methodologies. PMID:17447473

  1. Ambiguous value of anti-ganglioside IgM autoantibodies in Guillain-Barr syndrome and its variants.

    PubMed

    Koga, Michiaki; Takahashi, Masaki; Yokoyama, Keiko; Kanda, Takashi

    2015-08-01

    Anti-ganglioside autoantibodies of the IgG type are detected in a half of patients with Guillain-Barr syndrome (GBS), and their detection strongly supports the diagnosis of GBS. In contrast, anti-ganglioside IgM antibodies are also often detected in GBS patients, but it remains unclear whether IgM antibodies indicate a diagnosis of GBS. We identified four GBS patients (3.3%) who tested positive for IgM antibodies but negative for IgG antibodies among 122 patients with GBS and its variants. These four patients were all adolescents or young adults (age 13-22 years), experienced preceding gastrointestinal symptoms, and had serological and/or bacterial evidence of recent Campylobacter jejuni enteritis. Serum IgG reacted strongly with the lipo-oligosaccharide (LOS) of the C. jejuni isolates from these patients' stool specimens. Thin-layer chromatography with immunostaining showed that their serum IgG reacted with resorcinol-positive portion of LOS, suggesting that these patients had IgG autoantibodies against sialic acid-containing epitopes, probably unrecognized ganglioside-like structures on the bacterial LOS. We also examined anti-ganglioside autoantibodies in 22 patients with C. jejuni enteritis without subsequent neurological disorders and detected IgM antibodies in seven (32%) patients. Our data indicate that anti-ganglioside IgM antibodies can be detected in C. jejuni enteritis without complication of GBS, and that the detection of anti-ganglioside IgM antibodies does not always support a diagnosis of GBS. IgG autoantibodies against unrecognized gangliosides might play a role in the development of disease in patients with GBS in whom only anti-ganglioside IgM antibodies are detected by routine clinical testing. PMID:26050638

  2. Evaluation of the Abbott AxSYM cytomegalovirus (CMV) immunoglobulin M (IgM) assay in conjunction with other CMV IgM tests and a CMV IgG avidity assay.

    PubMed

    Lazzarotto, T; Galli, C; Pulvirenti, R; Rescaldani, R; Vezzo, R; La Gioia, A; Martinelli, C; La Rocca, S; Agresti, G; Grillner, L; Nordin, M; van Ranst, M; Combs, B; Maine, G T; Landini, M P

    2001-01-01

    The measurement of the avidity of cytomegalovirus (CMV) immunoglobulin G (IgG) antibodies has been shown by several investigators to be useful in identifying and excluding primary CMV infections in pregnant women. In this work, we examined the diagnostic utility of reflex testing of CMV IgM-positive specimens from pregnant women by using a CMV IgG avidity assay. The utility of this approach was directly dependent on the sensitivity of the CMV IgM assay employed during the initial screen. The higher initial reactivity rate of the AxSYM CMV IgM assay was necessary in order to detect CMV IgM in specimens containing low-avidity CMV IgG antibodies, indicative of a primary CMV infection, which other CMV IgM assays (Behring, Vidas, Captia, and Eurogenetics) fail to detect in some cases. The use of the AxSYM CMV IgM assay, followed by an avidity test, should result in more accurate diagnosis of CMV infection in pregnant women. PMID:11139220

  3. Generation, characterization and in vivo biological activity of two distinct monoclonal anti-PEG IgMs

    SciTech Connect

    Hashimoto, Yosuke; Shimizu, Taro; Mima, Yu; Abu Lila, Amr S.; Ishida, Tatsuhiro; Kiwada, Hiroshi

    2014-05-15

    PEGylation, the attachment of polyethylene glycol (PEG) to nanocarriers and proteins, is a widely accepted approach to improving the in vivo efficacy of the non-PEGylated products. However, both PEGylated liposomes and PEGylated proteins reportedly trigger the production of specific antibodies, mainly IgM, against the PEG moiety, which possibly leads to a reduction in safety and therapeutic efficacy of the PEGylated products. In the present study, two monoclonal anti-PEG IgMs — HIK-M09 via immunization with an intravenous injection of PEGylated liposomes (SLs) and HIK-M11 via immunization with a subcutaneous administration of PEGylated ovalbumin (PEG-OVA) were successfully generated. The generated IgMs showed efficient reactivity to mPEG{sub 2000} conjugated to 1,2-distearoyl-sn-glycero-3-phospho-ethanolamine (DSPE), PEGylated liposome (SL) and PEG-OVA. It appears that HIK-M09 recognizes ethoxy (OCH{sub 2}CH{sub 2}) repeat units along with a terminal motif of PEG, while HIK-M11 recognizes only ethoxy repeat units of PEG. Such unique properties allow HIK-M09 to bind with dense PEG. In addition, their impact on the in vivo clearance of the PEGylated products was investigated. It was found that the generated ant-PEG IgMs induced a clearance of SL as they were intravenously administered with SL. Interestingly, the HIK-M11, generated by PEG-OVA, induced the clearance of both SL and PEG-OVA, while the HIK-M09, generated by SL, induced the clearance of SL only. We here revealed that the presence of serum anti-PEG IgM and the subsequent binding of anti-PEG IgM to the PEGylated products are not necessarily related to the enhanced clearance of the products. It appears that subsequent complement activation following anti-PEG IgM binding is the most important step in dictating the in vivo fate of PEGylated products. This study may have implications for the design, development and clinical application of PEGylated products and therapeutics. - Highlights: • Two monoclonal anti-PEG IgMs were generated against distinct PEGylated materials. • In vivo cross-reactivity to the immunized materials was limited. • Although in vitro cross-reactivity of generated monoclonal IgMs has been confirmed.

  4. High affinity IgM(+) memory B cells are generated through a germinal center-dependent pathway.

    PubMed

    Hara, Yasushi; Tashiro, Yasuyuki; Murakami, Akikazu; Nishimura, Miyuki; Shimizu, Takeyuki; Kubo, Masato; Burrows, Peter D; Azuma, Takachika

    2015-12-01

    During a T cell-dependent immune response, B cells undergo clonal expansion and selection and the induction of isotype switching and somatic hypermutation (SHM). Although somatically mutated IgM(+) memory B cells have been reported, it has not been established whether they are really high affinity B cells. We tracked (4-hydroxy-3-nitrophenyl) acetyl hapten-specific GC B cells from normal immunized mice based on affinity of their B cell receptor (BCR) and performed BCR sequence analysis. SHM was evident by day 7 postimmunization and increased with time, such that high affinity IgM(+) as well as IgG(+) memory B cells continued to be generated up to day 42. In contrast, class-switch recombination (CSR) was almost completed by day 7 and then the ratio of IgG1(+)/IgM(+) GC B cells remained unchanged. Together these findings suggest that IgM(+) B cells undergo SHM in the GC to generate high affinity IgM(+) memory cells and that this process continues even after CSR is accomplished. PMID:26514429

  5. Circulating microparticles carry oxidation-specific epitopes and are recognized by natural IgM antibodies1[S

    PubMed Central

    Tsiantoulas, Dimitrios; Perkmann, Thomas; Afonyushkin, Taras; Mangold, Andreas; Prohaska, Thomas A.; Papac-Milicevic, Nikolina; Millischer, Vincent; Bartel, Caroline; Hörkkö, Sohvi; Boulanger, Chantal M.; Tsimikas, Sotirios; Fischer, Michael B.; Witztum, Joseph L.; Lang, Irene M.; Binder, Christoph J.

    2015-01-01

    Oxidation-specific epitopes (OSEs) present on apoptotic cells and oxidized low density lipoprotein (OxLDL) represent danger-associated molecular patterns that are recognized by different arcs of innate immunity, including natural IgM antibodies. Here, we investigated whether circulating microparticles (MPs), which are small membrane vesicles released by apoptotic or activated cells, are physiological carriers of OSEs. OSEs on circulating MPs isolated from healthy donors and patients with ST-segment elevation myocardial infarction (STE-MI) were characterized by flow cytometry using a panel of OSE-specific monoclonal antibodies. We found that a subset of MPs carry OSEs on their surface, predominantly malondialdehyde (MDA) epitopes. Consistent with this, a majority of IgM antibodies bound on the surface of circulating MPs were found to have specificity for MDA-modified LDL. Moreover, we show that MPs can stimulate THP-1 (human acute monocytic leukemia cell line) and human primary monocytes to produce interleukin 8, which can be inhibited by a monoclonal IgM with specificity for MDA epitopes. Finally, we show that MDA+ MPs are elevated at the culprit lesion site of patients with STE-MI. Our results identify a subset of OSE+ MPs that are bound by OxLDL-specific IgM. These findings demonstrate a novel mechanism by which anti-OxLDL IgM antibodies could mediate protective functions in CVD. PMID:25525116

  6. Factors Affecting Anti-Glycan IgG and IgM Repertoires in Human Serum.

    PubMed

    Muthana, Saddam M; Gildersleeve, Jeffrey C

    2016-01-01

    Serum anti-glycan antibodies play important roles in many immune processes and are of particular interest as biomarkers for many diseases. Changes in anti-glycan antibodies can occur with the onset of disease or in response to stimuli such as pathogens and vaccination. Understanding relationships between anti-glycan antibody repertoires and genetic and environment factors is critical for basic research and clinical applications, but little information is available. In this study we evaluated the effects of age, race, gender, and blood type on anti-glycan antibody profiles in the serum of 135 healthy subjects. As expected, IgG and IgM antibody signals to blood group antigens correlated strongly with blood type. Interestingly, antibodies to other non-ABH glycans, such as the alpha-Gal antigen, also correlated with blood type. A statistically significant decline in IgM signals with age was observed for many antibody subpopulations, but not for IgG. Moreover, statistically significant correlations between race and IgG levels to certain LacNAc-containing glycans were observed. The results have important implications for designing studies and interpreting results in the area of biomarker discovery and for the development of vaccines. The study also highlights the importance of collecting and reporting patient information that could affect serum anti-glycan antibody levels. PMID:26781493

  7. The role of colliding galaxies and tidal dwarf galaxies in the ISM/IGM enrichment

    NASA Astrophysics Data System (ADS)

    Duc, P.-A.

    This review discusses the processes associated with galaxy collisions that contribute to the enrichment of the interstellar and intergalactic medium. Chemical evolution is driven by two main effects: (a) local enrichment of the ISM/IGM following star formation episodes triggered by collisions, occurring in two main modes, (1) a nuclear starburst, which results in superwinds/outflows, with injection of metals up to the intergalactic medium, (2) extended star formation episodes locally enriching up to large distances the surrounding ISM, and even the IGM when occurring within extended tidal tails and in tidal dwarf galaxies (b) radial mixing of the gas, with (1) the funneling of metal-poor gas in the central regions and a dilution of the metals there, (2) the transport of pre-enriched dusty gas towards external regions including tidal structures. The net effect is a flattening of the metallicity gradient of colliding galaxies, which is predicted by numerical simulations and observed in real systems. The last part of the paper addresses and belittles the specific contribution of collisional debris, especially tidal dwarf galaxies, in the pollution of the Universe.

  8. Class switch recombination process in ataxia telangiectasia patients with elevated serum levels of IgM.

    PubMed

    Mohammadinejad, Payam; Abolhassani, Hassan; Aghamohammadi, Asghar; Pourhamdi, Shabnam; Ghosh, Sujal; Sadeghi, Bamdad; Nasiri Kalmarzi, Rasoul; Durandy, Anne; Borkhardt, Arndt

    2015-01-01

    Ataxia telangiectasia (AT) is a rare primary immunodeficiency disorder with various clinical manifestations. Increased serum levels of IgM and recurrent infections, mainly sinopulmonary infections, can be the presenting feature in a number of AT patients and may be initially misdiagnosed as hyper-IgM (HIgM) syndrome. This study was designed to investigate class switch recombination (CSR) as a critical mechanism in B lymphocytes' maturation to produce different isotypes of antibody in response to antigen stimulation in AT cases with HIgM presentation. Quantitative IgE production after stimulation by IL-4 and CD40L was considered as an indicator for CSR function. We also compared their results with sex and age matched AT patients without HIgM presentation. We report four AT patients with recurrent infections during infancy and high serum levels of IgM. Laboratory evaluations revealed defective CSR while none of the three AT patients without HIgM presentation had a defect in the CSR process. The characterized defect in AT is a mutation in the ataxia telangiectasia mutated (ATM) gene. This gene may result in CSR defects due to impaired DNA break repair. A special association between AT and HIgM may indicate a new subgroup of AT patients according to their clinical phenotype and CSR condition. PMID:24568663

  9. Factors Affecting Anti-Glycan IgG and IgM Repertoires in Human Serum

    PubMed Central

    Muthana, Saddam M.; Gildersleeve, Jeffrey C.

    2016-01-01

    Serum anti-glycan antibodies play important roles in many immune processes and are of particular interest as biomarkers for many diseases. Changes in anti-glycan antibodies can occur with the onset of disease or in response to stimuli such as pathogens and vaccination. Understanding relationships between anti-glycan antibody repertoires and genetic and environment factors is critical for basic research and clinical applications, but little information is available. In this study we evaluated the effects of age, race, gender, and blood type on anti-glycan antibody profiles in the serum of 135 healthy subjects. As expected, IgG and IgM antibody signals to blood group antigens correlated strongly with blood type. Interestingly, antibodies to other non-ABH glycans, such as the alpha-Gal antigen, also correlated with blood type. A statistically significant decline in IgM signals with age was observed for many antibody subpopulations, but not for IgG. Moreover, statistically significant correlations between race and IgG levels to certain LacNAc-containing glycans were observed. The results have important implications for designing studies and interpreting results in the area of biomarker discovery and for the development of vaccines. The study also highlights the importance of collecting and reporting patient information that could affect serum anti-glycan antibody levels. PMID:26781493

  10. Warm autoimmune hemolytic anemia associated with an IgM autoanti-Ge.

    PubMed

    Sererat, T; Veidt, D; Arndt, P A; Garratty, G

    1998-01-01

    A 28-year-old male with a prior history of Hodgkin's disease and a recent upper respiratory tract infection presented with autoimmune hemolytic anemia (AIHA). The patient's red blood cells (RBCs) were spontaneously agglutinated after room temperature and 37 degrees C washes. Dithiothreitol-treated RBCs reacted strongly with anti-C3 and were nonreactive with anti-IgG, -IgM, and -IgA; they reacted with anti-IgM (kappa light chains only) by flow cytometry. The patient's serum was nonreactive. An acid eluate was only weakly reactive, but a 56 degrees C heat eluate strongly agglutinated untreated RBCs (3+). Ficin-treated RBCs were nonreactive. En(a-) RBCs were strongly reactive, but Ge- RBCs were nonreactive. The anti-Ge in the eluate was IgM. The patient's untreated RBCs were shown, by flow cytometry, to be weakly Ge+. This is the first report of IgM-mediated warm AIHA associated with autoanti-Ge. PMID:15377210

  11. The etiology of Rubella IgM positivity in patients with rubella-like illness in Iran from 2011 to 2013.

    PubMed

    Khorrami, Seyed Mahmood Seyed; Mokhtari-Azad, Talat; Yavarian, Jila; Nasab, Gazal Sadat Fatemi; Naseri, Maryam; Jandaghi, Nazanin Zahra Shafiei

    2015-11-01

    Rubella is a mild self-limiting contagious viral disease caused by the rubella virus (RV). Although symptoms are often mild, the concern is centralized around the possible effect on a fetus growth and development in case of primary infection during early months of pregnancy. Recently acquired rubella is commonly confirmed by RV-specific IgM antibody detection in the serum. However, rubella primary infection is not always the only cause of IgM positivity. Other possible causes of rubella IgM positivity may include IgM persistence following vaccination or naturally acquired infection or even re-infection. Moreover, nonspecific IgM reactivity can cause false-positive results. There are few articles to differentiate the aetiology of rash in rubella-like illnesses. However, limited studies have been conducted on clarifying the source of IgM positivity in these cases. This article reports the study of 10,896 clinical cases demonstrating rubella-like illness between 2011 and 2013 in Iran. The rate of IgM positivity among these cases was 0.52% (57 cases). As predicted based on the high coverage of vaccination in Iran fewer than 16% of cases with ELISA IgM positive result, were due to current rubella primary infections. The greater part of the positive IgM reactions occurred in cross reactivity with other viruses (31.6%) or in prolonged IgM response post vaccination (24.6%). This research confirmed that the positive result of rubella IgM assay in vaccinated individuals is mainly caused by prolonged IgM production, rubella re-infection, and false positivity due to infection with other viruses, rather than the rubella primary infection itself. PMID:25950278

  12. 2D immunoblots show differential response of mouse IgG and IgM antibodies to antigens of mammary carcinoma 4 T1 cells

    PubMed Central

    2014-01-01

    Background Immunosuppression in breast cancer has been reported in women and in the highly metastatic mouse mammary tumor model 4 T1. The immunosuppressive environment complicates the use of the humoral response against the tumor as an immunodiagnostic tool. IgM has not been used in immunodiagnostic in part because its antitumor responses, both innate and adaptive, have not been studied in function of time in breast cancer. We show a new approach to analyzing the mouse humoral immune response, and compare the evolution with time of IgG and IgM responses against the antigens of 4 T1 cells. Methods The study is based on 2-dimensional immunoblotting detection of antigens from 4 T1 cells by the IgG and IgM antibodies in the serum of female mice injected with 4 T1 cells. Results There was a high variability in the intra-and inter-mouse response. Variability in the IgM response was manifested as a pattern of spots that could become a multibinomial variable of 0 and 1, which could represent a signature of the immune response. Different numbers of spots was found in the IgG and IgM responses from week 1 to 5. On average, the IgM had more but the IgG response decrease with the time. The natural IgM at t = 0 responds stronger than w1; the adaptive response of both IgM and IgG were elicited where, with the former being stronger better than the latter. Antigens that are recognized by some female mice in the first week are also recognized by other female mice at time 0. Contamination of the natural IgM makes difficult use the adaptive IgM as a tool for immunodiagnostic. Conclusions IgM and IgG response varied with the time and individuals. Spot variation in 2D pattern for the natural IgM could be expressed as a binomial signature, which opens up the way to correlate a particular pattern with resistance or susceptibility. This uncovers a battery of IgMs for each individual to confront cancer or infections. The possibility to differentiate between adaptive IgM antibodies from the natural IgM will allow investigation of the adaptive IgM for early immunodiagnosis. PMID:24467921

  13. Extensive diversification of IgH subclass-encoding genes and IgM subclass switching in crocodilians.

    PubMed

    Cheng, Gang; Gao, Yang; Wang, Tao; Sun, Yi; Wei, Zhiguo; Li, Lingxiao; Ren, Liming; Guo, Ying; Hu, Xiaoxiang; Lu, Yan; Wang, Xumin; Liu, Guiming; Zhang, Chenglin; Yu, Jun; Pan-Hammarstrm, Qiang; Hammarstrm, Lennart; Wu, Xiaobing; Li, Ning; Zhao, Yaofeng

    2013-01-01

    Crocodilians are a group of reptiles that are closely related to birds and are thought to possess a strong immune system. Here we report that the IgH locus in the Siamese crocodile and the Chinese alligator contains multiple ? genes, in contrast to other tetrapods. Both the ?2 and ?3 genes are expressed through class-switch recombination involving the switch region and germline transcription. Both IgM1 and IgM2 are present in the serum as polymers, which implies that IgM class switching may have significant roles in humoural immunity. The crocodilian ? genes are the first IgA-encoding genes identified in reptiles, and these genes show an inverted transcriptional orientation similar to that of birds. The identification of both ? and ? genes in crocodilians suggests that the IgH loci of modern living mammals, reptiles and birds share a common ancestral organization. PMID:23299887

  14. Prospective serological and clinical studies on infants born in Kuwait with an elevated IgM in cord blood*

    PubMed Central

    Al-Nakib, W.; Deverajan, L. V.; Thorburn, H.; Ibrahim, M. E. A.; Moussa, M. A. A.; Hathout, H.; Yousof, A. M.; Soufi, S.

    1985-01-01

    Little is known about congenital viral and toxoplasmal infections in the developing countries. This study attempts to provide preliminary data on such infections among Arab mothers and infants in Kuwait. Babies born with an elevated IgM in cord blood were selected at birth and then studied prospectively during the first year of life for serological and clinical evidence of viral and toxoplasmal infections. There appeared to be a significant association between the elevation of total cord blood IgM and the selection of cases with cytomegalovirus infection. Demonstration of specific IgM in cord sera was attempted, whenever possible, to provide further evidence of congenital infection and to exclude early postnatal infections. In 18.5% of cases there was an association between serological evidence of infection and certain clinical abnormalities. Apart from cytomegalovirus and rubella virus, no evidence was found for congenital infection by other viruses or toxoplasma in this study. PMID:3002652

  15. Prospective serological and clinical studies on infants born in Kuwait with an elevated IgM in cord blood.

    PubMed

    Al-Nakib, W; Deverajan, L V; Thorburn, H; Ibrahim, M E; Moussa, M A; Hathout, H; Yousof, A M; Soufi, S

    1985-01-01

    Little is known about congenital viral and toxoplasmal infections in the developing countries. This study attempts to provide preliminary data on such infections among Arab mothers and infants in Kuwait. Babies born with an elevated IgM in cord blood were selected at birth and then studied prospectively during the first year of life for serological and clinical evidence of viral and toxoplasmal infections. There appeared to be a significant association between the elevation of total cord blood IgM and the selection of cases with cytomegalovirus infection. Demonstration of specific IgM in cord sera was attempted, whenever possible, to provide further evidence of congenital infection and to exclude early postnatal infections. In 18.5% of cases there was an association between serological evidence of infection and certain clinical abnormalities. Apart from cytomegalovirus and rubella virus, no evidence was found for congenital infection by other viruses or toxoplasma in this study. PMID:3002652

  16. Evaluation of the new architect cytomegalovirus immunoglobulin M (IgM), IgG, and IgG avidity assays.

    PubMed

    Lagrou, K; Bodeus, M; Van Ranst, M; Goubau, P

    2009-06-01

    A panel of new cytomegalovirus (CMV) assays for use on the Architect instrument has been developed, including a CMV avidity assay based on a new technology. The purpose of this study was to compare the performance characteristics of the fully automated CMV immunoglobulin M (IgM), IgG, and IgG avidity tests on the Architect instrument with those of other available assays. A total of 503 consecutive fresh patient serum specimens (routine serum specimens) and 96 serum specimens from 33 pregnant women with a recent CMV primary infection (seroconversion serum specimens) were tested for CMV IgM and IgG by the Architect (Abbott), Vidas (BioMrieux), and Enzygnost (Siemens) assays. The seroconversion sera and 100 preselected serum specimens IgM negative and IgG positive by the AxSYM assay were also tested by the IgG avidity tests on the Architect and Vidas instruments. The relative agreements for CMV IgM determination with routine sera between the Architect assay and the Vidas, Enzygnost, and AxSYM assays were 97%, 94%, and 93%, respectively, for the CMV IgM tests and 99%, 98%, and 98%, respectively, for the CMV IgG tests. The specificities of the CMV IgG avidity test were 98% for the Architect assay and 76% for the Vidas assay. No high CMV IgG avidity test results were found within the first 3 months after seroconversion by either of those assays. The correlation between the results of the newly developed CMV IgM and IgG tests on the Architect instrument with the Vidas and Enzygnost assays was excellent (> or = 94%). The CMV IgG avidity test reliably excluded patients with recent infections and showed an excellent specificity (98%). PMID:19339470

  17. Studies on the structural and biological functions of the C?3 and C?4 domains of IgM

    PubMed Central

    Bubb, M. O.; Conradie, J. D.

    1978-01-01

    The development of methods for the production of intact C?3 and C?4 domains of IgM have made possible the assessment of some of their structural and biological functions. Antiserum against Fc? fragment detected both domains and illustrated their complete antigenic non-identity. Circular dichroism spectroscopy and the retention of antigenicity indicated that both domains had retained most of their native structure. No interaction of the type C?3C?3, C?4C?4 or C?3C?4 could be detected under non-dissociating conditions by analytical ultracentrifugation or molecular exclusion chromatography experiments. These results lead us to believe that the transmission of effector messages between the Fab and Fc parts of IgM takes place through structural changes at the quaternary level. C[unk]1-fixation experiments with IgM and several of its fragments and domains show that (a) the C?4 domain contains the C[unk]1-fixing site; (b) the high C[unk]1-fixing capacity of IgM or Fc5? cannot be explained on the basis of a simple accumulative model of complement fixing domains; (c) the C[unk]1-fixing site is independent of the native structure of the C?4 domain; (d) the C[unk]1-fixing site does not contain carbohydrate. Examination of the IgM receptor on the surface of human T lymphocytes show that (a) C?4 domain is primarily responsible for the reaction and C?3 domain has very little affinity; (b) native structure is essential for the reaction because reduction and alkylation of the C?4 domain destroyed both its original conformation and affinity for this receptor; (c) IgM and Fc5? had a much greater affinity for the receptor than monomeric subunits: (d) carbohydrate on C?4 domain is not involved in the affinity reaction. ImagesFigure 1Figure 2 PMID:417020

  18. IRAK-4 and MyD88 deficiencies impair IgM responses against T-independent bacterial antigens

    PubMed Central

    Maglione, Paul J.; Simchoni, Noa; Black, Samuel; Radigan, Lin; Overbey, Jessica R.; Bagiella, Emilia; Bussel, James B.; Bossuyt, Xavier; Casanova, Jean-Laurent; Meyts, Isabelle; Cerutti, Andrea; Picard, Capucine

    2014-01-01

    IRAK-4 and MyD88 deficiencies impair interleukin 1 receptor and Toll-like receptor (TLR) signaling and lead to heightened susceptibility to invasive bacterial infections. Individuals with these primary immunodeficiencies have fewer immunoglobulin M (IgM)+IgD+CD27+ B cells, a population that resembles murine splenic marginal zone B cells that mount T-independent antibody responses against bacterial antigens. However, the significance of this B-cell subset in humans is poorly understood. Using both a 610 carbohydrate array and enzyme-linked immunosorbent assay, we found that patients with IRAK-4 and MyD88 deficiencies have reduced serum IgM, but not IgG antibody, recognizing T-independent bacterial antigens. Moreover, the quantity of specific IgM correlated with IgM+IgD+CD27+ B-cell frequencies. As with mouse marginal zone B cells, human IgM+CD27+ B cells activated by TLR7 or TLR9 agonists produced phosphorylcholine-specific IgM. Further linking splenic IgM+IgD+CD27+ B cells with production of T-independent IgM, serum from splenectomized subjects, who also have few IgM+IgD+CD27+ B cells, had reduced antibacterial IgM. IRAK-4 and MyD88 deficiencies impaired TLR-induced proliferation of this B-cell subset, suggesting a means by which loss of this activation pathway leads to reduced cell numbers. Thus, by bolstering the IgM+IgD+CD27+ B-cell subset, IRAK-4 and MyD88 promote optimal T-independent IgM antibody responses against bacteria in humans. PMID:25320238

  19. Comparative evaluation of tests for detection of parvovirus B19 IgG and IgM.

    PubMed

    de Ory, Fernando; Minguito, Teodora; Echevarra, Juan Emilio; Del Mar Mosquera, Mara; Fuertes, Antonio

    2014-03-01

    The aim of this study was to evaluate enzyme immunoassays (EIA) (Euroimmun, Lbeck, Germany) and chemiluminiscent immunoassays (CLIA) (Diasorin, Saluggia, Italy) in their application to detect B19V-IgM and -IgG. For this purpose, one hundred and ninety samples were studied. Of them, 101 came from recent infection cases (B19V-specific IgM (86) and/or PCR (87), 42 from past infections, 18 from non-infected, and 29 from other viral recent infections (Epstein-Barr virus, measles, and rubella). Samples were characterized by capture (for IgM), or indirect (for IgG) EIA (Biotrin, Dublin, Ireland); indeterminate samples were classified by indirect immunofluorescence (IIF) (Biotrin). All the samples were used for testing IgM assays, and all but the cases from other viral infections were used for IgG tests. For IgM, CLIA, and EIA identified 76 and 62 of 86 IgM positives, respectively (sensitivity 88.4% and 72.1%). Considering B19V IgM negative samples, negative result was obtained in 95 and 92 of 104, being the specificity values of CLIA and EIA 91.3% and 88.5%, respectively. For IgG, CLIA and EIA identified correctly 114 and 115 of the 122 positive samples (sensitivity 93.4% and 94.3%, respectively), and 39 and 36 of 39 negative samples (specificity 100% and 92.3%). As conclusion, CLIA methods can be used in clinical laboratories as adequate alternatives to the well-established Biotrin EIAs. PMID:23763266

  20. Frequency of central lesions in polyneuropathy associated with IgM monoclonal gammopathy: an MRI, neurophysiological and immunochemical study.

    PubMed Central

    Lger, J M; Younes-Chennoufi, A B; Zuber, M; Bouche, P; Jauberteau, M O; Dormont, D; Danon, F; Baumann, N; Brunet, P

    1992-01-01

    CNS lesions were studied in polyneuropathy associated with IgM monoclonal gammopathy. Eleven out of 12 patients with IgM MGUS and one patient with Waldenstrom's disease had clinical and electrophysiological features indicating a demyelinating polyneuropathy. MRI showed CNS white matter lesions in two cases. Antibodies reacting against glycolipids present in CNS white matter were present in five cases, two of which had abnormal MRI. Central conduction times cortex-C7, obtained by magnetic stimulation, were prolonged in 3/8 patients, of which two patients had anti-CNS glycolipid antibodies. Images PMID:1538215

  1. Teleost Fish Mount Complex Clonal IgM and IgT Responses in Spleen upon Systemic Viral Infection

    PubMed Central

    Castro, Rosario; Jouneau, Luc; Pham, Hang-Phuong; Bouchez, Olivier; Giudicelli, Vronique; Lefranc, Marie-Paule; Quillet, Edwige; Benmansour, Abdenour; Cazals, Frdric; Six, Adrien; Fillatreau, Simon; Sunyer, Oriol; Boudinot, Pierre

    2013-01-01

    Upon infection, B-lymphocytes expressing antibodies specific for the intruding pathogen develop clonal responses triggered by pathogen recognition via the B-cell receptor. The constant region of antibodies produced by such responding clones dictates their functional properties. In teleost fish, the clonal structure of B-cell responses and the respective contribution of the three isotypes IgM, IgD and IgT remain unknown. The expression of IgM and IgT are mutually exclusive, leading to the existence of two B-cell subsets expressing either both IgM and IgD or only IgT. Here, we undertook a comprehensive analysis of the variable heavy chain (VH) domain repertoires of the IgM, IgD and IgT in spleen of homozygous isogenic rainbow trout (Onchorhynchus mykiss) before, and after challenge with a rhabdovirus, the Viral Hemorrhagic Septicemia Virus (VHSV), using CDR3-length spectratyping and pyrosequencing of immunoglobulin (Ig) transcripts. In healthy fish, we observed distinct repertoires for IgM, IgD and IgT, respectively, with a few amplified ? and ? junctions, suggesting the presence of IgM- and IgT-secreting cells in the spleen. In infected animals, we detected complex and highly diverse IgM responses involving all VH subgroups, and dominated by a few large public and private clones. A lower number of robust clonal responses involving only a few VH were detected for the mucosal IgT, indicating that both IgM+ and IgT+ spleen B cells responded to systemic infection but at different degrees. In contrast, the IgD response to the infection was faint. Although fish IgD and IgT present different structural features and evolutionary origin compared to mammalian IgD and IgA, respectively, their implication in the B-cell response evokes these mouse and human counterparts. Thus, it appears that the general properties of antibody responses were already in place in common ancestors of fish and mammals, and were globally conserved during evolution with possible functional convergences. PMID:23326228

  2. Association between haptoglobin and IgM levels and the clinical progression of caseous lymphadenitis in sheep

    PubMed Central

    2013-01-01

    Background Sheep caseous lymphadenitis (CLA), caused by Corynebacterium pseudotuberculosis (Cp), is associated with direct economic losses and presents significant zoonotic potential. Despite the importance of the disease, a satisfactory vaccine model has not been developed. Thus, this study aimed to investigate the association between haptoglobin (Hp) and IgM levels and the clinical progression of CLA in primarily infected sheep and in sheep immunized with Cp- secreted antigens adjuvanted with Quillaja saponaria saponins. These animals were kept with CLA-positive sheep to simulate natural exposure that occurs in field conditions. During the experiment, the Hp and IgM levels were monitored for 21 days, and the development of internal CLA lesions was investigated through necropsies on day182 post-immunization. Results Primarily infected sheep in Group 2 (inoculated with 2x105 Cp virulent strain) had higher Hp values between the first and ninth days post inoculation (PI) than sheep in Group 1 (control; P < 0.05). Immunized animals in Group 3 had significantly higher Hp values between the third and seventh days PI, compared with the control group (P < 0.01). Binary logistic regression (BLR) analysis of primarily infected sheep indicated an association between Hp concentration and CLA clinical progression: animals with high Hp values had 99.9% less risk of having CLA abscesses than animals with low Hp levels (Odds ratio = 0.001, P < 0.05). Both experimental groups had significantly higher IgM titers than the control group around the ninth and eleventh days PI (P < 0.05). The BLR analysis for immunized sheep indicated an association between IgM levels and clinical progression: sheep with high IgM titers had 100.0% less risk of having CLA abscesses than animals with low IgM levels (Odds ratio = 0.000, P < 0.05). Conclusions Resistance to C. pseudotuberculosis infection is supported by the early acute phase response, in which up-regulation of Hp and IgM were predictive of a lower risk of CLA lesion development. Because the immunogen used in this study induced a high production of both Hp and IgM, Q. saponaria saponin should be considered a promising candidate in vaccine formulations against sheep CLA. PMID:24330714

  3. Molecular cloning and characterization of secretory and membrane-bound IgM of turbot.

    PubMed

    Gao, Yuan; Yi, Yangyang; Wu, Haizhen; Wang, Qiyao; Qu, Jiangbo; Zhang, Yuanxing

    2014-10-01

    In recent years, increasing diseases especially bacterial diseases have brought a host of losses with the expansive cultivation of turbot (Scophthalmus maximus). In order to do more research about the immune system of turbot for better understanding the mechanism of resisting diseases, the immunoglobulin genes related to secretory and membrane-bound IgM (s-IgM and m-IgM) of turbot were cloned using homology sequences cloning and SMART RACE PCR method. The heavy chain of s-IgM cDNA is 1900 bp in length including a leader region, a variable region, four constant regions (CH1, CH2, CH3 and CH4) and a C-terminal while the cDNA of m-IgM is 1795 bp with the same leader region, variable region, three constant regions (CH1, CH2 and CH3) and two transmembrane regions (TM1 and TM2). The sequence of IgM gene was also obtained and the structure consisted of V-CH1-CH2-CH3-CH4-TM1-TM2 is similar to other fishes. The highest level of s-IgM expression was observed in spleen, followed by kidney, gills, eyes, skin of the healthy turbot whereas the same profile of m-IgM expression is found with low level. And s-IgM takes up dominant proportion of total IgM expression. Also the relative expressions of s-IgM and m-IgM were analyzed in turbot vaccinated with the live attenuated vaccine Vibrio anguillarum. Not only the transcriptions of both s-IgM and m-IgM in liver, spleen and kidney of turbot injected with V. anguillarum MVAV6203 were up-regulated but also the expressions of s-IgM and m-IgM in spleen, kidney, gut, skin and gills of bath-vaccinated turbot were increased. Comparing the ratio changes of relative expression of m-IgM and s-IgM in vaccinated turbot, we found that the proportion of m-IgM were increasing in both administration routes, which probably indicated that the increasing expression of m-IgM strengthen the phagocytic ability of B cells. PMID:25066925

  4. IgM peak independently predicts treatment-free survival in chronic lymphocytic leukemia and correlates with accumulation of adverse oncogenetic events.

    PubMed

    Rizzo, D; Chauzeix, J; Trimoreau, F; Woillard, J B; Genevieve, F; Bouvier, A; Labrousse, J; Poli, C; Guerin, E; Dmytruk, N; Remenieras, L; Feuillard, J; Gachard, N

    2015-02-01

    We examined the significance of IgM peaks in chronic lymphocytic leukemia (CLL), including its association with newly reported MYD88, BIRC3, NOTCH1 and SF3B1 mutations. A total of 27, 25, 41 and 57 patients with monoclonal IgM or IgG peaks (IgM and IgG groups), hypogammaglobulinemia (Hypo-γ group) and normal immunoglobulin serum levels (normal-γ group) were, respectively, included. IgM peaks were mainly associated with Binet stage C and the del(17p). Biased usage of IGHV3-48 was shared by both IgM and IgG groups. IGHV3-74 and IGHV4-39 gene rearrangements were specific for IgM and IgG peaks, respectively. SF3B1, NOTCH1, MYD88 and BIRC3 mutation frequencies were 12%, 4%, 2% and 2%, respectively, being over-represented in IgM, IgG and Hypo-γ groups for SF3B1, and being equal between normal-γ and IgM groups for MYD88. Overall, 76%, 87%, 49% and 42% of cases from IgM, IgG, Hypo-γ and normal-γ groups had at least one intermediate or poor prognosis genetic marker, respectively. By multivariate analysis, IgM peaks were associated with shorter treatment-free survival independently from any other univariate poor prognosis biological parameters, including IgG peaks, Hypo-γ, IGHV status, SF3B1 mutations, cytogenetics and lymphocytosis. Therefore, as with IgG peaks, IgM peaks aggravated the natural course of CLL, with increased accumulation of adverse genetic events. PMID:24943833

  5. Multicenter evaluation of the Elecsys Toxo IgG and IgM tests for the diagnosis of infection with Toxoplasma gondii

    PubMed Central

    Meylan, Pascal; Paris, Luc; Liesenfeld, Oliver

    2015-01-01

    Detection of IgG and IgM antibodies is commonly performed for the diagnosis of infection with Toxoplasma gondii. We determined the accuracy of the Elecsys Toxo IgG and IgM test at four European laboratories compared to local reference methods. Coefficients of variation for reproducibility ranged from 1.0 to 6.5% for IgG and from 0.8 to 3.2% for IgM. Seroconversion panels revealed high overall concordance with the reference tests. The Elecsys test detected IgG antibodies earlier than the Cobas Core IgG test in 19 of 47 panels; persisting IgM antibodies were observed in the VIDAS but not the Elecsys test in five of 47 panels. In 31.4% of latent stage sera with persistent IgM antibodies (positive LIASON IgM), the Elecsys IgM test gave negative results indicating increased clinical specificity. Sensitivity and specificity of the Elecsys IgG assay ranged from 99.45 to 100% and 87.5099.80%, respectively, and 91.1195.74 and 98.4599.79% for the Elecsys IgM assay, respectively. In conclusion, excellent reproducibility and accuracy make the Elecsys Toxo G and M tests highly suitable for the detection of anti-T. gondii IgG and IgM antibodies. The lower detection rates for persistent IgM in the Elecsys IgM test increase clinical specificity and decrease the need for follow-up testing. PMID:26185683

  6. RAG-1 and IgM Genes, Markers for Early Development of the Immune System in Olive Flounder, Paralichthys olivaceus

    PubMed Central

    Lee, Jang-Wook; Yang, Hyun; Noh, Jae Koo; Kim, Hyun Chul; Park, Choul-Ji; Park, Jong-Won; Hwang, In Joon; Kim, Sung Yeon; Lee, Jeong-Ho

    2014-01-01

    Fish larvae are immediately exposed to microbes from hatching to maturation of their lymphoid organs, therefore effective innate mechanisms is very important for survival. However, the knowledge of the development of immune system in fish is limited and in demand now. In vertebrates, recombination-activating gene 1 (RAG-1) and immunoglobulin M (IgM) have been considered as very useful markers of the physiological maturity of the immune system. In this study, the expression of the both genes was assessed throughout the early developmental stages of olive flounder larvae (5-55 dph) and used as markers to follow the development of immune system. RAG-1 and IgM mRNA expression was detectable at 5 dph and remained so until 55 dph. These patterns of expression may suggest that the olive flounder start to develop its function around 5 dph. Tissue distribution was found that both genes mRNAs are only expressed in the immune-related organ such as spleen, kidney and gill. The early detection of IgM mRNA led to the investigation of its presence in oocytes. Both RAG-1 and IgM mRNA transcripts were detected in unfertilized oocytes, suggesting that they are maternally transferred. The biological significance of such a phenomenon remains to be investigated. PMID:25949177

  7. Isolation and Characterization of IgM and IgY Antibodies from Plasma of Magellanic Penguins (Spheniscus magellanicus).

    PubMed

    Bizelli, Camila C; Silva, A Sandriana R; da Costa, Jessica D; Vanstreels, Ralph E T; Atzingen, Marina V; Santoro, Marcelo L; Fernandes, Irene; Catão-Dias, José L; Faquim-Mauro, Eliana L

    2015-03-01

    Infectious diseases such as aspergillosis, avian malaria, and viral infections are significant threats to the conservation of penguins, leading to morbidity and mortality of these birds both in captivity and in the wild. The immune response to such infectious diseases is dependent on different mechanisms mediated by cells and soluble components such as antibodies. Antibodies or immunoglobulins are glycoproteins that have many structural and functional features that mediate distinct effector immune functions. Three distinct classes of antibodies have been identified in birds: immunoglobulin A (IgA), immunoglobulin M (IgM), and immunoglobulin Y (IgY). In this study we aim to establish an efficient laboratory method to obtain IgM and IgY antibodies from plasma samples of healthy adult Magellanic penguins (Spheniscus magellanicus). The protocol was developed combining plasma delipidation, sequential precipitation with caprylic acid and ammonium sulfate, and size-exclusion chromatography. The efficiency of the protocol and the identity of the purified IgM and IgY antibodies were confirmed through enzyme-linked immunosorbent assay, Western blotting, one-dimensional and two-dimensional polyacrylamide gel electrophoresis, and lectin binding assay. Structural and physicochemical properties of IgM and IgY from Magellanic penguins were consistent with those of other avian species. This purification protocol will allow for more detailed studies on the humoral immunity of penguins and for the development of high specificity serologic assays to test Magellanic penguins for infectious pathogens. PMID:26292539

  8. IgM and IgG antibody response to Paracoccidioides brasiliensis in naturally infected wild armadillos (Dasypus novemcinctus).

    PubMed

    Fernandes, G F; Deps, P; Tomimori-Yamashita, J; Camargo, Z P

    2004-08-01

    We studied the extent to which wild nine-banded armadillos, Dasypus novemcinctus, produce immune humoral responses specifically directed against characteristic Paracoccidioides brasiliensis antigens. Such antibody production might reflect direct contact with the ecological microniche of P. brasiliensis, or might merely reflect inhalation of widely distributed airborne propagules. An enzyme-linked immunosorbent assay (ELISA) was designed containing purified glycoprotein gp43 and gp70 antigens from P. brasiliensis as well as cross-reactive antisera originally targeted against human IgM (mu chain) and armadillo anti-IgG (gamma-chain). It was used to detect and classify IgM and IgG antibodies to P. brasiliensis in the armadillo. In a serological survey of 47 wild armadillos, IgM antibodies to gp43 were detected in seven animals (14.8%), and IgG antibodies were detected in 20 (42.5%). IgM antibodies to gp70 were detected in 10 (21.3%) animals and IgG antibodies were detected in 18 (38.3%). These results, showing a pattern consistent with infection, suggest that P. brasiliensis is enzootic in armadillos. How the animals became exposed could not be determined. PMID:15473362

  9. Detection of antibodies of the IgM class in sera of patients recently infected with influenza viruses.

    PubMed Central

    Buchner, Y I; Heath, R B; Collins, J V; Pattison, J R

    1976-01-01

    Sucrose density gradient ultracentrifugation can be used to detect specific 19S antibodies of the IgM class in the sera of patients recently infected with influenza A virus, provided steps are taken to remove non-specific inhibitors of haemagglutination. The usefulness of the procedure for the diagnosis of influenza requires further evaluation. PMID:945303

  10. Introduction of germline residues improves the stability of anti-HIV mAb 2G12-IgM.

    PubMed

    Chromikova, Veronika; Mader, Alexander; Hofbauer, Stefan; Gbl, Christoph; Madl, Tobias; Gach, Johannes S; Bauernfried, Stefan; Furtmller, Paul G; Forthal, Donald N; Mach, Lukas; Obinger, Christian; Kunert, Renate

    2015-10-01

    Immunoglobulins M (IgMs) are gaining increasing attention as biopharmaceuticals since their multivalent mode of binding can give rise to high avidity. Furthermore, IgMs are potent activators of the complement system. However, they are frequently difficult to express recombinantly and can suffer from low conformational stability. Here, the broadly neutralizing anti-HIV-1 antibody 2G12 was class-switched to IgM and then further engineered by introduction of 17 germline residues. The impact of these changes on the structure and conformational stability of the antibody was then assessed using a range of biophysical techniques. We also investigated the effects of the class switch and germline substitutions on the ligand-binding properties of 2G12 and its capacity for HIV-1 neutralization. Our results demonstrate that the introduced germline residues improve the conformational and thermal stability of 2G12-IgM without altering its overall shape and ligand-binding properties. Interestingly, the engineered protein was found to exhibit much lower neutralization potency than its wild-type counterpart, indicating that potent antigen recognition is not solely responsible for IgM-mediated HIV-1 inactivation. PMID:25748881

  11. Immature chicken B cells with immunocompetence restricted to IgM type do not elicit the formation of germinal centres.

    PubMed Central

    Nishi, M; Yan, K; Bito, Y

    1983-01-01

    Chickens depleted of both T and B cells were restored with T cells and with immature B cells capable of producing IgM only, and immunized with sheep red blood cells. These chickens developed strikingly few germinal centres, in marked contrast to controls which received normal adult B cells. PMID:6606614

  12. Characterization of IgA and IgM binding and internalization by surface-expressed human Fc?/? receptor.

    PubMed

    Yoo, Esther M; Trinh, K Ryan; Lim, Hana; Wims, Letitia A; Morrison, Sherie L

    2011-09-01

    The Fc?/? receptor (Fc?/?R) is an unusual Fc receptor in that it binds to two different antibody isotypes, IgA and IgM. This receptor is of interest because it is thought to be involved in the capture of IgA- and IgM-immune complexes and antigen presentation. To further characterize this receptor, we were able to stably express human Fc?/?R on the surface of the 293T cell line. Using this system, we determined the affinity of the interactions of the receptor with IgA and IgM, which led to novel insights including the important finding that IgM polymers can bind to human Fc?/?R in the absence of J chain. This is in contrast to the polymeric immunoglobulin receptor (pIgR), which requires the presence of J chain to bind to polymeric IgA and IgM. The dissociation constants (K(d)) of all of the different human IgA isotypes and allotypes for human Fc?/?R were determined, and we show that the N-linked glycans on IgA1 are not required for binding to the receptor. In addition, we demonstrate that IgA can be rapidly internalized by human Fc?/?R in the presence of cross-linking antibody. PMID:21632111

  13. A patient with fever, abdominal pain and bicytopenia: Trouble once again with these IgM antibodies!

    PubMed

    Alidjinou, E K; Lazrek, M; Libier, L; Bocket, L; Dewilde, A; Engelmann, I; Hober, D

    2016-02-01

    We here report the case of a 30-year old man with a history of ulcerative colitis, who presented clinical and biological features compatible with a viral hepatitis. Initial serological results revealed the presence of IgM antibodies against many viruses, and the most likely diagnosis was viral hepatitis A. However, further investigations were performed and concluded to cytomegalovirus primary infection. PMID:26679224

  14. Introduction of germline residues improves the stability of anti-HIV mAb 2G12-IgM

    PubMed Central

    Chromikova, Veronika; Mader, Alexander; Hofbauer, Stefan; Göbl, Christoph; Madl, Tobias; Gach, Johannes S.; Bauernfried, Stefan; Furtmüller, Paul G.; Forthal, Donald N.; Mach, Lukas; Obinger, Christian; Kunert, Renate

    2015-01-01

    Immunoglobulins M (IgMs) are gaining increasing attention as biopharmaceuticals since their multivalent mode of binding can give rise to high avidity. Furthermore, IgMs are potent activators of the complement system. However, they are frequently difficult to express recombinantly and can suffer from low conformational stability. Here, the broadly neutralizing anti-HIV-1 antibody 2G12 was class-switched to IgM and then further engineered by introduction of 17 germline residues. The impact of these changes on the structure and conformational stability of the antibody was then assessed using a range of biophysical techniques. We also investigated the effects of the class switch and germline substitutions on the ligand-binding properties of 2G12 and its capacity for HIV-1 neutralization. Our results demonstrate that the introduced germline residues improve the conformational and thermal stability of 2G12-IgM without altering its overall shape and ligand-binding properties. Interestingly, the engineered protein was found to exhibit much lower neutralization potency than its wild-type counterpart, indicating that potent antigen recognition is not solely responsible for IgM-mediated HIV-1 inactivation. PMID:25748881

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

    PubMed Central

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

    2011-01-01

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

  16. Clinical evaluation of dengue RNA, NS1, and IgM for diagnosis of dengue in Southern China.

    PubMed

    Chen, Xinliang; Chen, Rui; Gu, Wenshen; He, Jian; Cai, Weipeng; Li, Jiajia; Duan, Chaohui; Yan, Haiyan

    2016-01-01

    In 2014, a large outbreak of dengue occurred in Guangzhou, China. This outbreak prompted us to evaluate NS1 and RNA for the early diagnosis of acute dengue infection, in addition to the combination with IgM antibody. We aimed to find the differences of three assays about dengue diagnosis. This study was an evaluation of diagnosis test. Based on WHO criteria 2009, dengue RNA, NS1, and IgM/IgG were detected from 294 patients (180 dengue patients, 114 non-dengue patients) by three diagnostic kits made in China. The χ(2) test, sensitivity, and specificity were used in statistical analysis. The ratios of dengue patients with low platelet counts (<100 × 10(9) /L 32.2%) or white blood cell counts (<4.0 × 10(9) /L 58.9%) were significantly higher compared to non-dengue patients (P < 0.05). Dengue NS1 was shown sensitive (93.9%) for diagnostic use. RNA had a better performance with 98.1% of sensitivity from day 1 to day 4 after illness onset. IgM performed better at day 5 or more with 74.0% of sensitivity. The diagnostic rate using a combination of RNA and IgM was 97.8% and 96.7% using NS1 and IgM. A patient with low platelet and white blood cell counts needs additional tests for dengue during an epidemic. RNA and NS1 were most valuable for early diagnosis of dengue, whereas IgM was best suited as a supplementary method for patients at day 5 or more after illness onset. PMID:26118588

  17. Diagnosis of recent hepatitis A infection: a comparison of two methods for detecting specific IgM.

    PubMed Central

    Mortimer, P. P.; Parry, J. V.; Appleton, H.

    1981-01-01

    Radioimmunoassay (RIA) tests for anti-hepatitis A virus (HAV) IgM were carried out on 728 sera: 283 were tested by both a method using an anti-mu serum bound to a solid phase and a method involving preliminary separation of igM by sucrose density gradient (SDG) centrifugation, 354 by the anti-mu method alone and two by the SDG method alone. Similar proportions of sera were found to be positive by each method (42.5%, 41.7%), but equivocal results were commoner by the SDG method (4.7% compared with 1.5%). There were 21 (5.5%) discrepant results from the sera tested by both methods, 20 of which could have been due to the higher sensitivity of the anti-mu method. The SDG method generally gave unequivocal results on sera collected within six weeks of the onset of jaundice. Separation of the IgM fraction by re-orientation centrifugation was quick, but otherwise offered no special advantage over separation on a swing-out rotor. The use of 2 mercaptoethanol (2 ME) reduction to assess the purity of the IgM fraction increased confidence in the specificity of the test. It led, however, to the exclusion of 16 reactive sera (4.2%), all of which were found to be positive in the anti-mu test. The anti-mu method gave better discrimination between positive and negative sera than the SDG method and detected IgM both earlier and later in infection. The results of tests designed to check the specificity of the anti-mu procedure were satisfactory. As it is potentially cheaper and easier to perform, the anti-mu method seems, in all respects, to be superior to the SDG method. PMID:6257778

  18. Investigating the function of Fc-specific binding of IgM to Plasmodium falciparum erythrocyte membrane protein 1 mediating erythrocyte rosetting.

    PubMed

    Stevenson, Liz; Huda, Pie; Jeppesen, Anine; Laursen, Erik; Rowe, J Alexandra; Craig, Alister; Streicher, Werner; Barfod, Lea; Hviid, Lars

    2015-06-01

    Acquired protection from Plasmodium falciparum malaria takes years to develop, probably reflecting the ability of the parasites to evade immunity. A recent example of this is the binding of the Fc region of IgM to VAR2CSA-type PfEMP1. This interferes with specific IgG recognition and phagocytosis of opsonized infected erythrocytes (IEs) without compromising the placental IE adhesion mediated by this PfEMP1 type. IgM also binds via Fc to several other PfEMP1 proteins, where it has been proposed to facilitate rosetting (binding of uninfected erythrocytes to a central IE). To further dissect the functional role of Fc -mediated IgM binding to PfEMP1, we studied the PfEMP1 protein HB3VAR06, which mediates rosetting and binds IgM. Binding of IgM to this PfEMP1 involved the Fc domains Cμ3-Cμ4 in IgM and the penultimate DBL domain (DBLζ2) at the C-terminus of HB3VAR06. However, IgM binding did not inhibit specific IgG labelling of HB3VAR06 or shield IgG-opsonized IEs from phagocytosis. Instead, IgM was required for rosetting, and each pentameric IgM molecule could bind two HB3VAR06 molecules. Together, our data indicate that the primary function of Fc -mediated IgM binding in rosetting is not to shield IE from specific IgG recognition and phagocytosis as in VAR2CSA-type PfEMP1. Rather, the function appears to be strengthening of IE-erythrocyte interactions. In conclusion, our study provides new evidence on the molecular details and functional significance of rosetting, a long-recognized marker of parasites that cause severe P. falciparum malaria. PMID:25482886

  19. Ionizing Radiation From Galaxies And The IGM At Z 2-3

    NASA Astrophysics Data System (ADS)

    Bogosavljevic, Milan; Steidel, C. C.

    2009-01-01

    We report on the direct spectroscopic observations of escaping Lyman continuum radiation in individual galaxy spectra drawn from a sample of rest-UV selected (Lyman Break) galaxies at z 3. The fraction of UV photons which manage to escape from galaxies at high redshift is a key parameter required for our understanding of re-ionization and the physical conditions in the IGM at z>2. Until now, there have been no spectroscopic observations available that would point to a relationship between this escape fraction and intrinsic galaxy properties. We have obtained very deep Keck LRIS-B ( 8-10hrs total exposure time) spectroscopy in the rest-frame UV for a sample of 120 galaxies at z 3, and we were able to directly measure the escaping Lyman continuum radiation in spectra of 13 sources. This spectroscopic sample in conjunction with optical and near-IR imaging allows us to investigate how properties such as star formation rate, stellar mass and UV morphology of galaxies relate to measurements of flux in the Lyman continuum. MB and CCS have been supported by the NSF through grants AST-0606912.

  20. Toxocara canis glycans influence antigen recognition by mouse IgG1 and IgM antibodies.

    PubMed

    Długosz, Ewa; Wiśniewski, Marcin

    2016-01-01

    The impact of sugar moieties of Toxocara canis glycoprotein antigens on their recognition by infected mouse antibodies was investigated in this study. Native TES and recombinant Toxocara mucins generated in Pichia pastoris yeast as well as their deglycosylated forms were used in ELISA. TES and recombinant mucins were equally recognized by T. canis infected mouse IgG1 antibodies. IgM immunoglobulins predominantly recognized TES antigens. Among mucins recognition of Tc-MUC-4 was the most significant. Deglycosylation of antigens resulted in significant loss of IgM and IgG1 reactivity to TES, mucins, Tc-MUC-3 and Tc-MUC-4. The presence of sugar moieties had no influence on IgE binding to native or recombinant T. canis antigens. Our results suggest that glycans are involved in epitope formation what should be taken into consideration in production of recombinant helminth antigens for diagnostic purposes. PMID:26751891

  1. Association of IgM monoclonal gammopathy with progressive muscular atrophy and multifocal motor neuropathy: a case-control study.

    PubMed

    Vlam, Lotte; Piepers, Sanne; Sutedja, Nadia A; Jacobs, Bart C; Tio-Gillen, Anne P; Stam, Marloes; Franssen, Hessel; Veldink, Jan H; Cats, Elisabeth A; Notermans, Nicolette C; Bloem, Andries C; Wadman, Renske I; van der Pol, W-Ludo; van den Berg, Leonard H

    2015-03-01

    Monoclonal gammopathy in patients with amyotrophic lateral sclerosis (ALS) and related disorders has been reported in small studies but the validity of the reported associations remains uncertain. Presence of monoclonal gammopathy may indicate specific pathogenic pathways and may facilitate the development of novel treatment strategies. The objective of this large case-control study was to determine the prevalence of monoclonal gammopathy in motor neuron diseases (MND) and multifocal motor neuropathy (MMN). Monoclonal gammopathy was determined by immunoelectrophoresis and immunofixation in serum from 445 patients with ALS, 158 patients with progressive muscular atrophy (PMA), 60 patients with primary lateral sclerosis (PLS), 88 patients with MMN and in 430 matched healthy controls. Anti-ganglioside antibody titers were determined in sera from patients with MMN and PMA, and in ALS and PLS patients with monoclonal gammopathy. Logistic regression analysis was used to investigate associations of monoclonal gammopathy with motor neuron diseases and clinical characteristics. Neither ALS nor PLS was associated with monoclonal gammopathy. IgM monoclonal gammopathy was more frequent in patients with PMA (8 %) (OR = 4.2; p = 0.001) and MMN (7 %) (OR = 5.8; p = 0.002) than in controls (2 %). High titers of anti-GM1 IgM antibodies were present in 43 % of MMN patients and 7 % of PMA patients. Patients with PMA and IgM monoclonal gammopathy or anti-GM1 antibodies had a higher age at onset, more often weakness of upper legs and more severe outcome than patients with MMN. PMA and MMN, but not ALS and PLS, are significantly associated with IgM monoclonal gammopathy and anti-GM1 antibodies. These results may indicate that a subset of patients presenting with PMA share pathogenic mechanisms with MMN. PMID:25549972

  2. Natural and adaptive IgM antibodies in the recognition of tumor-associated antigens of breast cancer (Review)

    PubMed Central

    DÍAZ-ZARAGOZA, MARIANA; HERNÁNDEZ-ÁVILA, RICARDO; VIEDMA-RODRÍGUEZ, RUBÍ; ARENAS-ARANDA, DIEGO; OSTOA-SALOMA, PEDRO

    2015-01-01

    For early detection of cancer, education and screening are important, but the most critical factor is the development of early diagnostic tools. Methods that recognize the warning signs of cancer and take prompt action lead to an early diagnosis; simple tests can identify individuals in a healthy population who have the disease but have not developed symptoms. Early detection of cancer is significant and is one of the most promising approaches by which to reduce the growing cancer burden and guide curative treatment. The early diagnosis of patients with breast cancer is challenging, since it is the most common cancer in women worldwide. Despite the advent of mammography in screening for breast cancer, low-resource, low-cost alternative tools must be implemented to complement mammography findings. IgM is part of the first line of defense of an organism and is responsible for recognizing and eliminating infectious particles and removing transformed cells. Most studies on breast cancer have focused on the development of IgG-like molecules as biomarkers or as a treatment for the advanced stages of cancer, but autoantibodies (IgM) and tumor-associated antigens (proteins or carbohydrates with aberrant structures) have not been examined as early diagnostic tools for breast cancer. The present review summarizes the function of natural and adaptive IgM in eliminating cancer cells in the early stages of pathology and their value as early diagnostic tools. IgM, as a component of the immune system, is being used to identify tumor-associated antigens and tumor-associated carbohydrate antigens. PMID:26133558

  3. Natural and adaptive IgM antibodies in the recognition of tumor-associated antigens of breast cancer (Review).

    PubMed

    Daz-Zaragoza, Mariana; Hernndez-vila, Ricardo; Viedma-Rodrguez, Rub; Arenas-Aranda, Diego; Ostoa-Saloma, Pedro

    2015-09-01

    For early detection of cancer, education and screening are important, but the most critical factor is the development of early diagnostic tools. Methods that recognize the warning signs of cancer and take prompt action lead to an early diagnosis; simple tests can identify individuals in a healthy population who have the disease but have not developed symptoms. Early detection of cancer is significant and is one of the most promising approaches by which to reduce the growing cancer burden and guide curative treatment. The early diagnosis of patients with breast cancer is challenging, since it is the most common cancer in women worldwide. Despite the advent of mammography in screening for breast cancer, low-resource, low-cost alternative tools must be implemented to complement mammography findings. IgM is part of the first line of defense of an organism and is responsible for recognizing and eliminating infectious particles and removing transformed cells. Most studies on breast cancer have focused on the development of IgG-like molecules as biomarkers or as a treatment for the advanced stages of cancer, but autoantibodies (IgM) and tumor-associated antigens (proteins or carbohydrates with aberrant structures) have not been examined as early diagnostic tools for breast cancer. The present review summarizes the function of natural and adaptive IgM in eliminating cancer cells in the early stages of pathology and their value as early diagnostic tools. IgM, as a component of the immune system, is being used to identify tumor-associated antigens and tumor-associated carbohydrate antigens. PMID:26133558

  4. DC-SIGNexpressing macrophages trigger activation of mannosylated IgM B-cell receptor in follicular lymphoma

    PubMed Central

    Amin, Rada; Mourcin, Frdric; Uhel, Fabrice; Pangault, Cline; Ruminy, Philippe; Dupr, Loic; Guirriec, Marion; Marchand, Tony; Fest, Thierry; Lamy, Thierry

    2015-01-01

    Follicular lymphoma (FL) results from the accumulation of malignant germinal center (GC) B cells leading to the development of an indolent and largely incurable disease. FL cells remain highly dependent on B-cell receptor (BCR) signaling and on a specific cell microenvironment, including T cells, macrophages, and stromal cells. Importantly, FL BCR is characterized by a selective pressure to retain surface immunoglobulin M (IgM) BCR despite an active class-switch recombination process, and by the introduction, in BCR variable regions, of N-glycosylation acceptor sites harboring unusual high-mannose oligosaccharides. However, the relevance of these 2 FL BCR features for lymphomagenesis remains unclear. In this study, we demonstrated that IgM+ FL B cells activated a stronger BCR signaling network than IgG+ FL B cells and normal GC B cells. BCR expression level and phosphatase activity could both contribute to such heterogeneity. Moreover, we underlined that a subset of IgM+ FL samples, displaying highly mannosylated BCR, efficiently bound dendritic cellspecific intercellular adhesion molecule-3grabbing nonintegrin (DC-SIGN), which could in turn trigger delayed but long-lasting BCR aggregation and activation. Interestingly, DC-SIGN was found within the FL cell niche in situ. Finally, M2 macrophages induced a DC-SIGNdependent adhesion of highly mannosylated IgM+ FL B cells and triggered BCR-associated kinase activation. Interestingly, pharmacologic BCR inhibitors abolished such crosstalk between macrophages and FL B cells. Altogether, our data support an important role for DC-SIGNexpressing infiltrating cells in the biology of FL and suggest that they could represent interesting therapeutic targets. PMID:26272216

  5. Crystal structure of a glycosylated Fab from an IgM cryoglobulin with properties of a natural proteolytic antibody.

    PubMed

    Ramsland, Paul A; Terzyan, Simon S; Cloud, Gwendolyn; Bourne, Christina R; Farrugia, William; Tribbick, Gordon; Geysen, H Mario; Moomaw, Carolyn R; Slaughter, Clive A; Edmundson, Allen B

    2006-05-01

    The 2.6 A (1 A=0.1 nm) resolution structure has been determined for the glycosylated Fab (fragment antigen binding) of an IgM (Yvo) obtained from a subject with Waldenstrm's macroglobulinaemia. Dynamic light scattering was used to estimate the gel point and monitor the formation of an ordered hydroscopic gel of Yvo IgM upon cooling. If a cryoglobulin forms gels in peripheral tissues and organs, the associated swelling and damage to microvasculature can result in considerable morbidity and mortality. The three-dimensional structure of the branched N-linked oligosaccharide associated with the CH1 domain (first constant domain of heavy chain) is reported. The carbohydrate may act to shield part of the lateral surface of the CH1 domain and crowd the junction between the CH1 and CH2 domains, thereby limiting the segmental flexibility of the Fab arms in intact Yvo IgM, especially at low temperatures. Recently, Yvo IgM was shown to have the properties of a naturally occurring proteolytic antibody [Paul, Karle, Planque, Taguchi, Salas, Nishiyama, Handy, Hunter, Edmundson and Hanson (2004) J. Biol. Chem. 279, 39611-39619; Planque, Bangale, Song, Karle, Taguchi, Poindexter, Bick, Edmundson, Nishiyama and Paul (2004) J. Biol Chem. 279, 14024-14032]. The Yvo protein displayed the ability to cleave, by a nucleophilic mechanism, the amide bonds of a variety of serine protease substrates and the gp120 coat protein of HIV. An atypical serine, arginine and glutamate motif is located in the middle of the Yvo antigen-binding site and displays an overall geometry that mimics the classical serine, histidine and aspartate catalytic triad of serine proteases. Our present findings indicate that pre-existing or natural antibodies can utilize at least one novel strategy for the cleavage of peptide bonds. PMID:16422668

  6. DC-SIGN-expressing macrophages trigger activation of mannosylated IgM B-cell receptor in follicular lymphoma.

    PubMed

    Amin, Rada; Mourcin, Frdric; Uhel, Fabrice; Pangault, Cline; Ruminy, Philippe; Dupr, Loic; Guirriec, Marion; Marchand, Tony; Fest, Thierry; Lamy, Thierry; Tarte, Karin

    2015-10-15

    Follicular lymphoma (FL) results from the accumulation of malignant germinal center (GC) B cells leading to the development of an indolent and largely incurable disease. FL cells remain highly dependent on B-cell receptor (BCR) signaling and on a specific cell microenvironment, including T cells, macrophages, and stromal cells. Importantly, FL BCR is characterized by a selective pressure to retain surface immunoglobulin M (IgM) BCR despite an active class-switch recombination process, and by the introduction, in BCR variable regions, of N-glycosylation acceptor sites harboring unusual high-mannose oligosaccharides. However, the relevance of these 2 FL BCR features for lymphomagenesis remains unclear. In this study, we demonstrated that IgM(+) FL B cells activated a stronger BCR signaling network than IgG(+) FL B cells and normal GC B cells. BCR expression level and phosphatase activity could both contribute to such heterogeneity. Moreover, we underlined that a subset of IgM(+) FL samples, displaying highly mannosylated BCR, efficiently bound dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN), which could in turn trigger delayed but long-lasting BCR aggregation and activation. Interestingly, DC-SIGN was found within the FL cell niche in situ. Finally, M2 macrophages induced a DC-SIGN-dependent adhesion of highly mannosylated IgM(+) FL B cells and triggered BCR-associated kinase activation. Interestingly, pharmacologic BCR inhibitors abolished such crosstalk between macrophages and FL B cells. Altogether, our data support an important role for DC-SIGN-expressing infiltrating cells in the biology of FL and suggest that they could represent interesting therapeutic targets. PMID:26272216

  7. Increase in Anti-Gal IgM Level is Associated With Early Graft Failure in Intraportal Porcine Islet Xenotransplantation

    PubMed Central

    Lee, Haneulnari; Park, Eun Mi; Kim, Jong Min; Shin, Jun-Seop; Kim, Jung-Sik; Park, Chung-Gyu; Kim, Sang Joon

    2015-01-01

    Background Anti-Gal is a major antibody induced in non-human primates (NHPs) after xenotransplantation. To understand the mechanism of graft rejection, we investigated the association between anti-Gal responses and graft failure in NHP recipients of porcine islet transplantation (PITx). Methods Intraportal PITx was performed in 35 diabetic NHPs, and graft function was monitored. Early graft failure (EGF) was defined as loss of graft function within a month after PITx. Seven, 19, nine NHPs received immunosuppression (IS) without CD40 pathway blockade (Group I), with anti-CD154 (Group II), and with anti-CD40 (Group III), respectively. The anti-Gal levels on day 0 and day 7 of PITx were measured by ELISA. Results The frequency of EGF was significantly lower in Group II (26.3%) than in Group I (100%, P=0.0012) and Group III (77.8%, P=0.0166). While levels of anti-Gal IgG in Group I and anti-Gal IgM in Group III increased on day 7 compared with day 0 (P=0.0156 and 0.0273), there was no increase in either on day 7 in Group II. The ratio of anti-Gal IgM or IgG level on day 7 to that on day 0 (Ratio7/0) was significantly higher in recipients with EGF than without EGF (P=0.0009 and 0.0027). ROC curve analysis of anti-Gal IgM Ratio7/0 revealed an area under the curve of 0.789 (P=0.0003). Conclusions IS with anti-CD154 suppressed anti-Gal responses and prevented EGF in PITx. Anti-Gal IgM Ratio7/0, being associated with EGF, is a predictive marker for EGF. PMID:26354349

  8. A detector system for SPIDR, A mission to perform spectroscopy and photometry of the IGM's diffuse radiation

    NASA Astrophysics Data System (ADS)

    Lapington, Jonathan S.; Chakrabarti, Supriya; Cook, Timothy A.; Goeke, Robert F.; Gsell, J. C.; Gsell, V. T.

    2003-02-01

    The primary goal of the Spectroscopy and Photometry of the IGM's Diffuse Radiation (SPIDR) Mission is to detect and map the huge filamentary structures, the "cosmic web", predicted to be present in the IGM. The SPIDR instrument comprises six imaging spectrographs providing 8 x 8 and 2.5 x 2.5 high-resolution spatial maps of IGM features in the OVI and CIV wavelength bands. For simplicity and economy all six spectrographs utilize virtually identical detector systems. Each detector records a two-dimensional image whose axes represent spectral and one-dimensional spatial information, the second spatial axis being obtained by tomographic reconstruction. We describe the design of the prototype detector built for the SPIDR mission. The detector uses a conventional microchannel plate (MCP) arrangement with a charge division readout anode used in the image charge configuration. The image charge technique provides enhanced resolution, linearity and stability in a more compact mechanical design. The predictable distribution of the induced image charge footprint has allowed us to accurately simulate the readout performance in software. The conservative requirements of the SPIDR spectrograph allow the use of a conventional wedge and strip anode which benefits from the design improvements generated using our software simulation. Redesign of the boundary electrodes has enabled us to improve overall linearity and increase useful imaging area. We describe the integrated electronics system for the SPIDR prototype, designed for low mass and power consumption. A single printed circuit board is used to house analog signal processing, digital processing, and power systems.

  9. Comparative study of immunochromatographic assay (IgM) and widal test for early diagnosis of typhoid fever.

    PubMed

    Sultana, S; Hossain, M A; Alam, M A; Paul, S K; Kabir, M R; Hoque, S M; Yesmin, T; Habiba, U; Sarkar, S R; Maruf, M A; Halim, P I; Hoque, M R

    2012-10-01

    Typhoid fever is a severe systemic infection endemic in many developing countries, including Bangladesh. Present study evaluated immunochromatographic test (ICT) and Widal test in the early diagnosis of typhoid fever cases. The study was carried out in the department of Microbiology, Mymensingh Medical College, Mymensingh between July, 2010 and June, 2011, including 200 individuals of different age and sex. Of them, 150 were clinically suspected cases of typhoid fever and 50 age-sex matched controls. Among 150 blood samples from the suspected cases 106(70.7%) were positive for IgM of Salmonella typhi by ICT and 67(44.7%) were positive by Widal test. Whereas, among the 50 controls 4(8%) were positive by ICT and 6(12%) were positive by Widal test. The sensitivity, specificity, positive and negative predictive value of the ICT was found as 83.3%, 92.00%, 91.9% and 83.6% respectively. On the other hand corresponding values for Widal test were of 44.4%, 88%, 80% and 59.5% respectively. Thus, The ICT (IgM) is better alternative to Widal test for early and accurate diagnosis of typhoid fever. The ICT (IgM) is rapid, easy to perform, applicable for field use and highly sensitive and specific for detection of antibodies in patients with typhoid fever. PMID:23134904

  10. Novel B cell population producing functional IgG in the absence of membrane IgM expression.

    PubMed

    Orinska, Zane; Osiak, Anna; Löhler, Jürgen; Bulanova, Elena; Budagian, Vadim; Horak, Ivan; Bulfone-Paus, Silvia

    2002-12-01

    Surface expression of IgM is a characteristic feature of the development of most B cells. Only pre-B cells bearing functional IgM heavy chains mu chains) are selected for clonal expansion and differentiation. Cells lacking mu chains are normally eliminated. muMT mice carrying a deletion of the first exon coding for the transmembrane domain of the immunoglobulin mu chain gene were described as mice deficient for mature B cells, plasma cells and immunoglobulins in serum. In this study, we describe in muMT/BALB/c mice the presence of a novel B cell population, producing IgG, IgA and IgE in the absence of IgM membrane expression. Moreover, this small population of B cells is able to recognize antigens and to differentiate into plasma cells. These "non-conventional" mu(- / -) B cells produce functional immunoglobulins after immunization, undergo germinal center reactions, and maintain B cell memory. Our findings support the concept, that a small percentage of mu -non-expressing pre-B cells can escape elimination, switch to downstream immunoglobulin heavy chains and respond to antigens. It remains an open question how the reactivity of these B cells is regulated and in which extent such B cells play a role in physiological and pathological processes such as autoantibody production and autoimmunity. PMID:12442329

  11. A Research Standard for Human Serum Immunoglobulins IgG, IgA and IgM

    PubMed Central

    Rowe, D. S.; Anderson, S. G.; Grab, B.

    1970-01-01

    A pooled human serum, partly diluted, has been distributed into ampoules and freeze-dried in several batches. The freeze-dried material has been examined in an international collaborative assay and certain properties have also been estimated in individual laboratories. On the basis of these tests this material was considered to be suitable for use as a standard for the estimation of IgG, IgA and IgM for clinical purposes using the single-radial-diffusion or similar techniques. Greater uniformity of results than is obtained at present should be achieved if this material were in general use. Estimates of immunoglobulins from different laboratories using this material as a standard showed small but significant variability. This variability was probably related to the heterogeneity of immunoglobulins and of antisera, and it limits the precision of immunoglobulin estimations by techniques at present in use. Batches of this material have been distributed to various centres. 67/68 has been established as the British research standard for human serum immunoglobulins IgG, IgA and IgM for which the unit of potency is defined as the activity present in 0.8147 mg of dry powder. The average activity per ampoule of 67/86 is 100 units of IgG, IgA and IgM. The average activities of other related preparations have been estimated. ImagesFIG. 2 PMID:4194813

  12. IgM-class rheumatoid factor interference in the solid-phase radioimmunoassay of rubella-specific IgM antibodies.

    PubMed Central

    Meurman, O H; Ziola, B R

    1978-01-01

    The interference of IgM-class rheumatoid factor (RF) in the solid-phase radioimmunoassay (RIA) of rubella virus IgM antibodies was studied. Acute rubella infections did not significantly activate RF. False-positive rubella antibody results were obtained, however, when patients with raised RF levels were tested. If a low rubella IgG antibody titre was present, a high level of RF was required to cause a false-positive IgM result; conversely, in sera with high IgG titres, only a low level of RF was required for interference. Although the false-positive IgM titres obtained were generally low, thet did show a positive correlation to both RF levels and rubella IgG titres. False-positive results were successfully avoided by removing the RF by absorption with heat-aggregated human gamma globulin. The absorption procedure did not affect true rubella IgM antibody titres. PMID:77280

  13. Cross-Reactivity of Rapid Salmonella Typhi IgM Immunoassay in Dengue Fever Without Co-Existing Infection

    PubMed Central

    Ali, Farhan; Satti, Siddique Akbar

    2015-01-01

    Introduction: Dengue fever is endemic in developing nations worldwidewith as many as 500,000 annual cases of dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS).A prompt and accurate diagnosis early in the disease course is essential for prompt identification and treatment of severe complications of the dengue virus infection (DVI).We identified cross-reactivity of a rapid IgM test for typhoid fever in patients with febrile illnesses that were determined to be due to dengue virus. Methods: All patients with documented DVIduring a recent epidemic in Pakistan also underwent diagnostic testing forSalmonella entericaserovar Typhi.The diagnosis ofDVI was made based on clinical findings and the positive results for dengue non-structural protein 1 antigen (NS1Ag) and/or dengue IgM antibody (anti-D IgM) during the acute phase of febrile illness.Patients with positive test results for Salmonella typhi (S. Typhi) IgM also had their blood cultures done. Results: In the group of 322 patients with clinical and serological evidence of DVI, 107 also tested positive forS. TyphiIgM.Blood cultures were negative forS. Typhibacteria in all patients.Principal disease features included fever, headache, myalgia, retro-orbital pain, and a rash accompanied by thrombocytopenia and leukopenia.Comparisons of clinical and routine laboratory findings between theS. Typhi-positive and negative groups showed no significant differences. Patients testing positive for both NS1Agand anti-D IgM were significantly more likely to test positive forS. TyphiIgM, even in the absence oftyphoid fever.No routine antibiotics were used and all patients survived. Conclusion: One-third of a large group of patients with primary DVI also demonstrated false positive results for typhoid fever. Cross-reactivity of a rapid immunoassay for typhoid fever has not been previously reported in DVI or any other flavivirus infections. Until these findings can be further evaluated, clinicians should be cautious in interpretingS. Typhirapid immunoassays and have a high index of suspicion of DVI in dengue fever endemic areas.

  14. Mucosal memory B cells retain the ability to produce IgM antibodies 2 years after oral immunization.

    PubMed Central

    Vajdy, M; Lycke, N

    1995-01-01

    In recent studies we have demonstrated that immunological B- and T-cell memory may be stimulated effectively by oral immunization, simply by admixing protein antigens with cholera toxin (CT) adjuvant. Here we extend information by employing a hapten-carrier system allowing us to separate B- and T-cell memory and to evaluate the requirement of memory T cells for effective reactivation of mucosal memory B cells. We found that 2 weeks following oral priming immunizations with dinitrophenyl-keyhole limpet haemocyanin (DNP-KLH) plus CT adjuvant, significant serum anti-DNP antibodies of IgG, IgA and IgM immunoglobulin classes were demonstrated. However, after 2 years only IgM anti-DNP antibodies could still be detected in serum. When memory lymphocytes were isolated from these mice, from both systemic and gut-associated lymphoid tissues, and challenged with antigen in vitro, vigorous IgM, but no IgG or IgA, anti-DNP production was observed. By contrast, when the DNP-KHL-primed memory mice were challenged in vivo by an oral booster immunization with DNP-KLH plus CT adjuvant, strong systemic IgG and local mucosal IgA anti-DNP responses were recorded, while IgM anti-DNP production was poor. Moreover, the mucosal memory B cells from DNP-KHL-immunized mice were more responsive in vivo to an oral booster immunization with the carrier-specific antigen, DNP-KLH, compared to that provided by an unrelated carrier, DNP-human serum albumin (HSA), which gave only poor mucosal and systemic anti-DNP B-cell responses. Taken together our data suggest that mucosal memory B cells are recirculating cells that have retained their ability to produce IgM antibodies and, therefore, have not undergone switch differentiation involving gene rearrangements with constant mu-chain deletions. Furthermore, mucosal B-cell memory and CD4+ T-cell memory are closely interconnected phenomena, requiring both components for effective expression and probably also for maintenance of immunological memory in the mucosal immune system. PMID:8550068

  15. ABO (histo) blood group phenotype development and human reproduction as they relate to ancestral IgM formation: A hypothesis.

    PubMed

    Arend, Peter

    2016-01-01

    The formation of a histo (blood) group) ABO phenotype and the exclusion of an autoreactive IgM or isoagglutinin activity arise apparently in identical glycosylation of complementary domains on cell surfaces and plasma proteins. The fundamental O-glycan emptiness of the circulating IgM, which during the neonatal amino acid sequencing of the variable regions is exerting germline-specific O-GalNAc glycan-reactive serine/threonine residues that in the plasma of the adult human blood group O individuals apparently remain associated with the open glycosidic sites on the ABOH convertible red cell surface, must raise suggestions on a transient expression of developmental glycans, which have been "lost" over the course of maturation. In fact, while the mammalian non-somatic, embryogenic stem cell (ESC)- germ cell (GC) transformation is characterized by a transient and genetically as-yet-undefined trans-species-functional O-GalNAc glycan expression, in the C57BL/10 mouse such expression was potentially identified in growth-dependent, blood group A-like GalNAc glycan-bearing, ovarian glycolipids complementary with the syngeneic anti-A reactive IgM, which does not appear in early ovariectomized animals. This non-somatically encoded, polyreactive, ancestral IgM molecule has not undergone clonal selection and does primarily not differentiate between self and non-self and might, due to amino acid hydroxyl groups, highly suggest substrate competition with subsequent O-glycosylations in ongoing ESC-GC transformations and affecting GC maturation. However, the membrane-bound somatic N/O-glycotransferases, which initiate, after formation of the zygote, the complex construction of the human ABO phenotypes in the trans cisternae of the Golgi apparatus, are associated and/or completed with soluble enzyme versions exerting identical specificities in plasma and likely competing vice versa by glycosylation of neonatal IgM amino acids, where they suggest to accomplish the clearance of anti-A autoreactivity at germline serine and threonine residues. Sustaining the lineage-maintaining position of the classic A allele and the discovery of the OA hybrid alleles at the normal ABO locus and in heterozygous ESC lines have, together with clinical observations, raised discussions about a silent A-allelic support within blood group O reproduction. However, the question of whether a fictional "continued blood group O inbreeding" ultimately occurs without the A-allelic or somatic function remains unanswered because the genetic relationship between non-somatic O-GalNAc-glycosylations that operate before sperm-egg recognition and somatic O-GalNAc-glycosylations that arise after the formation of the zygote remains to be elucidated. PMID:26433867

  16. Anti-Streptococcus IgM Antibodies Induce Repetitive Stereotyped Movements: Cell Activation and Co-Localization with Fc?/? Receptors in the Striatum and Motor Cortex

    PubMed Central

    Zhang, Danhui; Patel, Ankur; Zhu, Youhua; Siegel, Allan; Zalcman, Steven S.

    2012-01-01

    Group A beta-hemolytic streptococcus (GABHS) infections are implicated in neuropsychiatric disorders associated with an increased expression of repetitive stereotyped movements. Anti-streptococcus IgG presumably cross-reacts with elements on basal ganglia cells, modifies their function, and triggers symptoms. IgM may play a unique role in precipitating behavioral disturbances since variations in cortico-striatal activity occur in temporal congruity with peak IgM titers during an orchestrated immune response. We discovered in Balb/c mice that single subcutaneous injections of mouse monoclonal IgM antibodies to Streptococcus Group A bacteria induce marked dose-dependent increases in repetitive stereotyped movements, including head bobbing, sniffing, and intense grooming. Effects were antibody- and antigen-specific: anti-streptococcus IgG stimulated ambulatory activity and vertical activity but not these stereotypies, while anti-KLH IgM reduced activity. We suggest that anti-streptococcus IgM and IgG play unique roles in provoking GABHS-related behavioral disturbances. Paralleling its stereotypy-inducing effects, anti-streptococcus IgM stimulated Fos-like immunoreactivity in regions linked to cortico-striatal projections involved in motor control, including subregions of the caudate, nucleus accumbens, and motor cortex. This is the first evidence that anti-streptococcus IgM antibodies induce in vivo functional changes in these structures. Moreover, there was a striking similarity in the distributions of anti-streptococcus IgM deposits and Fos-like immunoreactivity in these regions. Of further importance, Fc?/? receptors, which bind IgM, were present- and co-localized with anti-streptococcus IgM in these structures. We suggest that anti-streptococcus IgM-induced alterations of cell activity reflect local actions of IgM that involve Fc?/? receptors. These findings support the use of anti-streptococcus monoclonal antibody administration in Balb/c mice to model GABHS-related behavioral disturbances and identify underlying mechanisms. PMID:22285613

  17. Fetal lambs are depleted of IgM+ cells following a single injection of an anti-IgM antibody early in gestation.

    PubMed Central

    Press, C M; Reynolds, J D; McClure, S J; Simpson-Morgan, M W; Landsverk, T

    1996-01-01

    B-cell depleted fetal sheep were created following a single injection of an anti-IgM monoclonal antibody early in gestation. Six sheep fetuses were given a single intraperitoneal injection of a monoclonal antibody directed against IgM at 63 days of gestation (gestation in sheep = 150 days). The fetuses were killed at 138-142 days of gestation and lymphoid tissues were collected for subsequent light microscopy and immunohistochemical examination. The ileal and jejunal Peyer's patch (PP) follicles in four of the six injected fetuses were markedly reduced in size. Cells in the rudimentary follicles of the ileal PP of these animals showed no reactivity for IgM and most were negative for CD45. The dome regions contained many T cells, which were predominantly CD8+ cells and included gamma delta T cells. The interfollicular areas of the PP of the markedly affected fetuses contained large populations of T cells. The spleen and lymph nodes were also markedly depleted of IgM+ cells and these tissues contained only a small, scattered population of weakly IgM+ cells. Follicular accumulations of IgM+ cells were absent. Large populations of T cells were present in the white pulp of the spleen and cortex of the lymph nodes. The liver did not contain IgM+ cells and the medulla of the thymus was depleted of IgM+ cells. The results of this study suggest that a surface IgM+ B-cell population is present in the sheep fetus at 63 days of gestation, which is essential for the colonization of the ileal PP and subsequent B-cell development. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:8707346

  18. A new bioluminescent assay for studies of protein G and protein A binding to IgG and IgM.

    PubMed

    Zatta, P F

    1996-04-01

    It has been reported that protein G (PrG) specifically binds to IgG, but not to IgM. In the present paper, I report that using a bioluminescent immunoassay, that utilizes the recombinant calcium-dependent protein, Aequorin, as a photoprobe, IgM as well as IgG binds to PrG. The method presented here may also be used in general to study the glycosylation of proteins. PMID:8773543

  19. Diagnostic value of detecting specific IgA and IgM with recombinant Trypanosoma cruzi antigens in congenital Chagas' disease.

    PubMed

    Lorca, M; Veloso, C; Munoz, P; Bahamonde, M I; Garcia, A

    1995-06-01

    The present study compares the early diagnosis of congenital Chagas' disease with a DOT assay using recombinant antigens with immunofluorescence antibody testing (IFAT) and an enzyme-linked immunosorbent assay (ELISA). The studies were performed using cord blood and sera of 12 infected newborns (group I) and 12 uninfected ones born to Trypanosoma cruzi-infected mothers (group II). Conventional IFAT and ELISA showed positive results for IgG at high titers, in infants and mothers of both groups; IgA antibodies were detected by ELISA in four of the infected infants and IgM was detected in two of them. All sera of the uninfected infants were negative for IgA and IgM in the ELISA. Application of a DOT assay using eight recombinant T. cruzi antigens allowed detection of specific IgA in the cord blood of six of the infected cases and IgM in eight of them. Repetition of these serologic tests in samples obtained during a monthly follow-up gave positive results for IgA in two of the initially negative infants of group I and for IgM in four of them. This means that diagnosis of congenital T. cruzi infection was confirmed, through demonstration of specific IgM, in all infected infants, and of IgA in eight of them. The importance of late detection of IgM in siblings born of infected mothers is discussed. The detection of IgM and IgA in sera obtained after birth is believed to be due to a congenital transmission of the parasite that occurred late in pregnancy. No IgA or IgM antibodies could be detected by the DOT assay in the sera of the negative controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7611556

  20. IgM but not IgG monoclonal anti-Nocardia brasiliensis antibodies confer protection against experimental actinomycetoma in BALB/c mice.

    PubMed

    Gonzalez-Suarez, Maria L; Salinas-Carmona, Mario C; Pérez-Rivera, Isabel

    2009-10-01

    Nocardia brasiliensis is a facultative intracellular microorganism that produces a human chronic infection known as actinomycetoma. Human and mouse anti-N. brasiliensis antibody response identify P24, P26 and P61 immunodominant antigens. In this work, we generated immunoglobulin M (IgM) and IgG monoclonal antibodies (mAbs) specific to immunodominant P61 antigen. The monoclonal IgM (NbM1) and IgG2a (NbG1) antibodies were assessed for their in vitro bactericidal activity, in vivo protective effect and ability to block catalase activity. These mAbs specifically recognized P61, but they did not inhibit its enzyme activity. The in vitro bactericidal effect of NbG1 was higher than the killing ability of the IgM mAb. In vivo experiments with a murine model of experimental infection with N. brasiliensis injected into rear footpads was used to test the effect of NbM1 and NbG1. The negative untreated group developed a chronic actinomycetoma within 4 weeks. IgM mAbs conferred protection to BALB/c mice infected with N. brasiliensis. IgG mAb lacked this protective effect. IgM mAb showed a dose-response correlation between antibody concentration and lesion size. These results demonstrate that humoral immune response mediated by antigen-specific IgM antibody protects against an intracellular bacterial infection. PMID:19624737

  1. The carboxyl-terminal domains of IgA and IgM direct isotype-specific polymerization and interaction with the polymeric immunoglobulin receptor.

    PubMed

    Braathen, Ranveig; Sorensen, Vigdis; Brandtzaeg, Per; Sandlie, Inger; Johansen, Finn-Eirik

    2002-11-01

    Mucosal surfaces are protected by polymeric immunoglobulins that are transported across the epithelium by the polymeric immunoglobulin receptor (pIgR). Only polymeric IgA and IgM containing a small polypeptide called the "joining" (J) chain can bind to the pIgR. J chain-positive IgA consists of dimers, and some larger polymers, whereas only IgM pentamers incorporate the J chain. We made domain swap chimeras between human IgA1 and IgM and found that the COOH-terminal domains of the heavy chains (Calpha3 and Cmu4, respectively) dictated the size of the polymers formed and also which polymers incorporated the J chain. We also showed that chimeric IgM molecules engineered to contain Calpha3 were able to bind the rabbit pIgR. Since the rabbit pIgR normally does not bind IgM, these results suggest that the COOH-terminal domain of the polymeric immunoglobulins is primarily responsible for interaction with the pIgR. Finally, we made a novel chimeric IgA immunoglobulin, containing the terminal domain from IgM. This recombinant molecule formed J chain-containing pentamers that could, like IgA, efficiently form covalent complexes with the human pIgR ectodomain, known as secretory component. PMID:12213814

  2. Pregnancy Outcomes of Mothers with Detectable CMV-Specific IgM Antibodies: A Three-Year Review in a Large Irish Tertiary Referral Maternity Hospital

    PubMed Central

    Drew, Richard J.; Stapleton, Patrick; Abu, Hala; Healy, Eibhlín; Ferguson, Wendy; De Gascun, Cillian; O'Gorman, Joanne; Eogan, Maeve

    2015-01-01

    A retrospective audit was performed for all obstetric patients who had positive CMV IgM results between January 2012 and December 2014 in the Rotunda Hospital, Ireland. In total, 622 CMV IgM positive tests were performed on samples from 572 patients. Thirty-seven patients had a positive CMV IgM result (5.9%) on the Architect system as part of the initial screening. Three patients were excluded as they were not obstetric patients. Of the 34 pregnant women with CMV IgM positive results on initial screening, 16 (47%) had CMV IgM positivity confirmed on the second platform (VIDAS) and 18 (53%) did not. In the 16 patients with confirmed positive CMV IgM results, four (25%) had acute infection, two (12.5%) had infection of uncertain timing, and ten (62.5%) had infection more than three months prior to sampling as determined by the CMV IgG avidity index. Two of the four neonates of women with low avidity IgG had CMV DNA detected in urine. Both these cases had severe neurological damage and the indication for testing their mothers was because the biparietal diameter (BPD) was less than the 5th centile at the routine 20-week gestation anomaly scan. PMID:26696757

  3. V region gene analysis of human IgM hybridoma monoclonal anti-Sm antibodies.

    PubMed

    Mahmoudi, M; Edwards, J Y; Bell, D A; Cairns, E

    1997-01-01

    Anti-Sm antibodies although highly specific for systemic lupus erythematosus can only be found in 10-25% of lupus patients and lupus-prone MRL/lpr mice. Molecular studies of these autoantibodies from mice have suggested that the anti-Sm response is Ag driven, its expression is controlled by stochastic events and may originate from the same B cell precursors as anti-DNA antibodies. However, relatively little information regarding the molecular characteristics of anti-Sm antibodies in man has been reported. We studied the V region genes of three IgM hybridoma monoclonal antibodies (BUD 45.12.8, BUD 114.4.11 and BUD 94.91.8) which were selected for Sm reactivity and derived from B cells of a healthy child. Two of these antibodies BUD 45.12.8 and BUD 114.4.11 also-reacted with ssDNA, while the third (BUD 94.91.8) did not. Each of these anti-Sm/ RNP antibodies was encoded by different and predominantly unmutated Ig heavy chain germline genes (BUD 45.12.8 by VH3-23, DXP4 and JH4b; BUD 94.91.8 by VH3-33, D21-9 and JH6b; BUD 114.4.11 by VH1-2, DK1 or DM1 or unknown D and JH4b) and light chain genes (BUD 45.12.8 by Humkv325 and JK2; BUD 94.91.8 by hsiggll150 (lambda IIIb) and J lambda 2/3; BUD 114.4.11 by Humk18 and JK3). Many of these genes are also used by antibodies with other specificities including DNA. The two anti-Sm antibodies which also bound ssDNA shared an overall V region net positive charge, while the third antibody without ssDNA reactivity carried a negative V region net charge. These findings demonstrate that (1) normal individuals have the genetic potential to generate autoantibodies to Sm/RNP; (2) acquisition of Sm/RNP binding is not dependent on somatic mutations and (3) some human B cell clones exhibit specificity for Sm and ssDNA. PMID:9302661

  4. Cross-reactions in IgM ELISA tests to Legionella pneumophila sg1 and Bordetella pertussis among children suspected of legionellosis; potential impact of vaccination against pertussis?

    PubMed Central

    2015-01-01

    The objective of this study was preliminary evaluation of IgM cross-reaction in sera collected from children hospitalized because of suspected legionellosis. Sera with positive IgM results to L. pneumophila sgs1-7, B. pertussis or with simultaneous detection of IgM antibodies to L. pneumophila sgs1-7 and B. pertussis, or IgM to L. pneumophila sgs1-7 and M. pneumoniae in routine tests, were selected. In total, an adapted pre-absorption test was used for the serological confirmation of legionellosis in the sera of 19 children suspected of legionellosis, and also in 3 adult persons with confirmed Legionnaires’ disease. Sera were pre-absorbed with antigens of L. pneumophila sg1, B. pertussis or both, and tested by ELISA tests. The reduction of IgM antibody level by pre-absorption with antigen/antigens was determined. Reduction of anti-Lpsgs1-7 IgM by pre-absorption with L.pneumophila sg1 antigen ranged from 1.5 to 80, and reduction of anti-Bp IgM by pre-absorption with B. pertussis ranged from 2.0 to 23.8. Reduction by both antigens varied depending on the age of the patients: among children <4 yrs.old, the reduction of anti-B. pertussis IgM by both antigens was higher than for B. pertussis antigen alone. Based on the high difference (≥ 2 times) between reduction by L.pneumophila sg1 and by B. pertussis antigen, legionellosis was confirmed in 8/19 children. The majority of them also indicated IgM positive/borderline results for B. pertussis or M.pneumoniae in routine ELISA tests. As a preliminary, we posed a hypothesis of a potential impact of an anti-pertussis vaccination on the results obtained in anti-L. pneumophila ELISA IgM tests among young children. PMID:26557032

  5. Generation and characterization of antibodies against Asian elephant (Elephas maximus) IgG, IgM, and IgA.

    PubMed

    Humphreys, Alan F; Tan, Jie; Peng, RongSheng; Benton, Susan M; Qin, Xiang; Worley, Kim C; Mikulski, Rose L; Chow, Dar-Chone; Palzkill, Timothy G; Ling, Paul D

    2015-01-01

    Asian elephant (Elephas maximus) immunity is poorly characterized and understood. This gap in knowledge is particularly concerning as Asian elephants are an endangered species threatened by a newly discovered herpesvirus known as elephant endotheliotropic herpesvirus (EEHV), which is the leading cause of death for captive Asian elephants born after 1980 in North America. While reliable diagnostic assays have been developed to detect EEHV DNA, serological assays to evaluate elephant anti-EEHV antibody responses are lacking and will be needed for surveillance and epidemiological studies and also for evaluating potential treatments or vaccines against lethal EEHV infection. Previous studies have shown that Asian elephants produce IgG in serum, but they failed to detect IgM and IgA, further hampering development of informative serological assays for this species. To begin to address this issue, we determined the constant region genomic sequence of Asian elephant IgM and obtained some limited protein sequence information for putative serum IgA. The information was used to generate or identify specific commercial antisera reactive against IgM and IgA isotypes. In addition, we generated a monoclonal antibody against Asian elephant IgG. These three reagents were used to demonstrate that all three immunoglobulin isotypes are found in Asian elephant serum and milk and to detect antibody responses following tetanus toxoid booster vaccination or antibodies against a putative EEHV structural protein. The results indicate that these new reagents will be useful for developing sensitive and specific assays to detect and characterize elephant antibody responses for any pathogen or vaccine, including EEHV. PMID:25658336

  6. An atypical IgM class platelet cold agglutinin induces GPVI-dependent aggregation of human platelets.

    PubMed

    Snchez Guiu, I M; Martnez-Martinez, I; Martnez, C; Navarro-Fernandez, J; Garca-Candel, F; Ferrer-Marn, F; Vicente, V; Watson, S P; Andrews, R K; Gardiner, E E; Lozano, M L; Rivera, J

    2015-08-01

    Platelet cold agglutinins (PCA) cause pseudothrombocytopenia, spurious thrombocytopenia due to ex vivo platelet clumping, complicating clinical diagnosis, but mechanisms and consequences of PCA are not well defined. Here, we characterised an atypical immunoglobulin (Ig)M PCA in a 37-year-old woman with lifelong bleeding and chronic moderate thrombocytopenia, that induces activation and aggregation of autologous or allogeneic platelets via interaction with platelet glycoprotein (GP)VI. Patient temperature-dependent pseudothrombocytopenia was EDTA-independent, but was prevented by integrin ?IIb?3 blockade. Unstimulated patient platelets revealed elevated levels of bound IgM, increased expression of activation markers (P-selectin and CD63), low GPVI levels and abnormally high thromboxane (TX)A2 production. Patient serum induced temperature- and ?IIb?3-dependent decrease of platelet count in allogeneic donor citrated platelet-rich plasma (PRP), but not in PRP from Glanzmann's thrombasthenia or afibrinogenaemia patients. In allogeneic platelets, patient plasma induced shape change, P-selectin and CD63 expression, (14)C-serotonin release, and TXA2 production. Activation was not inhibited by aspirin, cangrelor or blocking anti-Fc receptor (Fc?RIIA) antibody, but was abrogated by inhibitors of Src and Syk, and by a soluble GPVI-Fc fusion protein. GPVI-deficient platelets were not activated by patient plasma. These data provide the first evidence for an IgM PCA causing platelet activation/aggregation via GPVI. The PCA activity persisted over a five-year follow-up period, supporting a causative role in patient chronic thrombocytopenia and bleeding. PMID:25994029

  7. Generation and Characterization of Antibodies against Asian Elephant (Elephas maximus) IgG, IgM, and IgA

    PubMed Central

    Humphreys, Alan F.; Tan, Jie; Peng, RongSheng; Benton, Susan M.; Qin, Xiang; Worley, Kim C.; Mikulski, Rose L.; Chow, Dar-Chone; Palzkill, Timothy G.; Ling, Paul D.

    2015-01-01

    Asian elephant (Elephas maximus) immunity is poorly characterized and understood. This gap in knowledge is particularly concerning as Asian elephants are an endangered species threatened by a newly discovered herpesvirus known as elephant endotheliotropic herpesvirus (EEHV), which is the leading cause of death for captive Asian elephants born after 1980 in North America. While reliable diagnostic assays have been developed to detect EEHV DNA, serological assays to evaluate elephant anti-EEHV antibody responses are lacking and will be needed for surveillance and epidemiological studies and also for evaluating potential treatments or vaccines against lethal EEHV infection. Previous studies have shown that Asian elephants produce IgG in serum, but they failed to detect IgM and IgA, further hampering development of informative serological assays for this species. To begin to address this issue, we determined the constant region genomic sequence of Asian elephant IgM and obtained some limited protein sequence information for putative serum IgA. The information was used to generate or identify specific commercial antisera reactive against IgM and IgA isotypes. In addition, we generated a monoclonal antibody against Asian elephant IgG. These three reagents were used to demonstrate that all three immunoglobulin isotypes are found in Asian elephant serum and milk and to detect antibody responses following tetanus toxoid booster vaccination or antibodies against a putative EEHV structural protein. The results indicate that these new reagents will be useful for developing sensitive and specific assays to detect and characterize elephant antibody responses for any pathogen or vaccine, including EEHV. PMID:25658336

  8. Multiplex Microsphere Immunoassays for the Detection of IgM and IgG to Arboviral Diseases

    PubMed Central

    Basile, Alison J.; Horiuchi, Kalanthe; Panella, Amanda J.; Laven, Janeen; Kosoy, Olga; Lanciotti, Robert S.; Venkateswaran, Neeraja; Biggerstaff, Brad J.

    2013-01-01

    Serodiagnosis of arthropod-borne viruses (arboviruses) at the Division of Vector-Borne Diseases, CDC, employs a combination of individual enzyme-linked immunosorbent assays and microsphere immunoassays (MIAs) to test for IgM and IgG, followed by confirmatory plaque-reduction neutralization tests. Based upon the geographic origin of a sample, it may be tested concurrently for multiple arboviruses, which can be a cumbersome task. The advent of multiplexing represents an opportunity to streamline these types of assays; however, because serologic cross-reactivity of the arboviral antigens often confounds results, it is of interest to employ data analysis methods that address this issue. Here, we constructed 13-virus multiplexed IgM and IgG MIAs that included internal and external controls, based upon the Luminex platform. Results from samples tested using these methods were analyzed using 8 different statistical schemes to identify the best way to classify the data. Geographic batteries were also devised to serve as a more practical diagnostic format, and further samples were tested using the abbreviated multiplexes. Comparative error rates for the classification schemes identified a specific boosting method based on logistic regression Logitboost as the classification method of choice. When the data from all samples tested were combined into one set, error rates from the multiplex IgM and IgG MIAs were <5% for all geographic batteries. This work represents both the most comprehensive, validated multiplexing method for arboviruses to date, and also the most systematic attempt to determine the most useful classification method for use with these types of serologic tests. PMID:24086608

  9. IGM CONSTRAINTS FROM THE SDSS-III/BOSS DR9 Lyα FOREST TRANSMISSION PROBABILITY DISTRIBUTION FUNCTION

    SciTech Connect

    Lee, Khee-Gan; Hennawi, Joseph F.; Spergel, David N.; Weinberg, David H.; Hogg, David W.; Viel, Matteo; Bolton, James S.; Bailey, Stephen; Carithers, William; Schlegel, David J.; Pieri, Matthew M.; Lundgren, Britt; Palanque-Delabrouille, Nathalie; Yèche, Christophe; Schneider, Donald P.

    2015-02-01

    The Lyα forest transmission probability distribution function (PDF) is an established probe of the intergalactic medium (IGM) astrophysics, especially the temperature-density relationship of the IGM. We measure the transmission PDF from 3393 Baryon Oscillations Spectroscopic Survey (BOSS) quasars from Sloan Digital Sky Survey Data Release 9, and compare with mock spectra that include careful modeling of the noise, continuum, and astrophysical uncertainties. The BOSS transmission PDFs, measured at (z) = [2.3, 2.6, 3.0], are compared with PDFs created from mock spectra drawn from a suite of hydrodynamical simulations that sample the IGM temperature-density relationship, γ, and temperature at mean density, T {sub 0}, where T(Δ) = T {sub 0}Δ{sup γ} {sup –} {sup 1}. We find that a significant population of partial Lyman-limit systems (LLSs) with a column-density distribution slope of β{sub pLLS} ∼ – 2 are required to explain the data at the low-transmission end of transmission PDF, while uncertainties in the mean Lyα forest transmission affect the high-transmission end. After modeling the LLSs and marginalizing over mean transmission uncertainties, we find that γ = 1.6 best describes the data over our entire redshift range, although constraints on T {sub 0} are affected by systematic uncertainties. Within our model framework, isothermal or inverted temperature-density relationships (γ ≤ 1) are disfavored at a significance of over 4σ, although this could be somewhat weakened by cosmological and astrophysical uncertainties that we did not model.

  10. [Evaluation of a rapid IgM antibody detection kit for diagnosis of Mycoplasma pneumoniae infection during childhood].

    PubMed

    Narita, Mitsuo; Togashi, Takehiro

    2003-05-01

    We evaluated the utility of a rapid detection kit for Mycoplasma pneumoniae (Mp)-specific IgM antibody, ImmunoCard (IC) Mycoplasma Test (Meridian Bioscience, USA), with regard to mycoplasmal infection during childhood. For this purpose, 30 serum samples were obtained from 23 pediatric patients with serologically proved mycoplasmal pneumonia at and younger than 16 years of age. The diagnosis of mycoplasmal infection was made by means of a particle agglutination (PA) method, which was on the basis of 1) a four fold or greater rise with paired sera or 2) at and more than 1:640 with a single, acute phase serum. In addition to the IC test, Mp-specific IgM and IgG antibodies were measured by ELISA tests (Zeus, USA) for comparison. A final observation time for colorization in the IC test was prolonged to 10 min in this study. The reason for this was because only 8 samples which were obtained 5 days or more after the onset of fever (37.5 degrees C) were judged to be positive when the observation time was confined to 5 min as the manufacturer recommended. A judgment was always made by more than one persons. Since we intended to find out the diagnostic capability of the IC test using an acute phase single serum, we focused on 18 cases for which samples were obtained within 5 days of the onset of fever. As a result, 13 (72%) cases were judged to be positive for Mp by the IgM ELISA test, 6 (33%) cases, including 5 cases in which the result was interpreted to be positive by a 10-min observation, were judged to be positive by the IC test, and 4 (22%) cases were judged to be positive by the PA test when titers of at and more than 1:320 by an acute phase single serum were interpreted as significant. Through this study we felt that the sensitivity of the IC test was not so high as have been previously reported in the literatures (the IC test was occasionally positive even in the range of < 1:40 by a PA test). On the other hand, we believe that the 10-min observation for final colorization did not significantly affect the specificity of the IC test as long as it was compared with the results by the ELISA IgM test. So far, the rapidity in obtaining results, and the simplicity of handling by which the test can be performed in an outpatient clinic, are thought to be the major advantages of the IC test. PMID:12806926

  11. Serum carbohydrate-binding IgM are present in Vietnamese striped catfish (Pangasianodon hypophthalmus) but not in North African catfish (Clarias gariepinus).

    PubMed

    Giang, Duong Thi Huong; Van Driessche, Edilbert; Beeckmans, Sonia

    2012-02-01

    Pangasianodon hypophthalmus serum was fractionated by affinity chromatography on 12 different Sepharose-carbohydrate columns and proteins eluted by the corresponding sugar. Binding to the affinity matrices is dependent on Ca(2+) ions. Upon gel filtration using Superose-12, essentially one fraction was obtained, eluting as a protein with a molecular mass of about 900 kDa. SDS-PAGE in reducing conditions revealed the presence of large (72 kDa) subunits (H-chains) and one up to three small (24, 26 and/or 28-29 kDa) subunits (L-chains). The isolated proteins were shown to be IgM since they bind monoclonal anti-P. hypophthalmus IgM antibodies. Rabbit polyclonal anti-galactose-binding IgM only cross-react with some sugar-binding IgM. The H-chains of the anti-carbohydrate IgM are glycosylated. Circular dichroism studies revealed that the IgMs have an "all-?" type of structure, and that Ca(2+) ions, though essential for carbohydrate-binding activity, are not required for the structural integrity of the molecules. In non-reducing SDS-PAGE, only monomers and halfmers were obtained, showing that there are no disulfide bonds linking the monomers, and that a disulfide bond connecting both H-chains within one monomer is only present in 45% of the molecules. Both the monomers and the halfmers display molecular mass heterogeneity which is indicative for redox forms at the level of the intradomain disulfide bonds. The native carbohydrate-binding IgMs agglutinate erythrocytes from different animals, as well as fish pathogenic bacteria. Similar proteins could not be isolated from another catfish, Clarias gariepinus. PMID:21911003

  12. Natural IgM Anti-Leukocyte Auto-Antibodies (IgM-ALA) Attenuate Excess Inflammation Mediated by Innate and Adaptive Immune Mechanisms Involving TH-17

    PubMed Central

    Lobo, Peter I.; Bajwa, Amandeep; Schlegel, Kailo H.; Vengal, John; Lee, Sang J.; Huang, Liping; Ye, Hong; Deshmukh, Umesh; Wang, Tong; Pei, Hong; Okusa, Mark D.

    2011-01-01

    Little is known about the function of natural IgM auto-antibodies and especially IgM with anti-leukocyte reactivity (IgM-ALA). Natural IgM-ALA auto-antibodies are present at birth and characteristically increase during inflammatory and infective conditions. Our prior clinical observations and those of others showing less rejections in renal and cardiac allografts transplanted into recipients with high levels of IgM-ALA, led us to investigate if IgM-ALA regulate the inflammatory response. Here we show that IgM, in physiologic doses, inhibit pro-inflammatory cells from proliferating and producing IFN-γ and IL-17 in response to alloantigens (MLR), anti-CD3 and the glycolipid alpha-gal ceramide. We show in an IgMko murine model, with intact B cells and Tregs, that there is more severe inflammation and loss of function in absence of IgM after renal ischemia reperfusion injury (IRI) and cardiac allograft rejection. Replenishing IgM in IgMko or increasing the levels of IgM-ALA in WT-B6 mice significantly attenuated the inflammation in both these inflammatory models which involve IFN-γ and IL-17. The protective effect on renal IRI wasnot observed using IgM pre-adsorbed with leukocytes to remove IgM-ALA. We provide data to show that the anti-inflammatory effect of IgM is in part mediated by inhibiting TLR4 induced NF-kB translocation into the nucleus and inhibiting differentiation of activated T cells into TH-1 and TH-17 cells. These observations highlight the importance of IgM-ALA in regulating excess inflammation mediated by both innate and adaptive immune mechanisms and where the inflammatory response involves TH-17 cells that are not effectively regulated by Tregs. PMID:22262657

  13. Rapid Proliferation and Differentiation of a Subset of Circulating IgM Memory B Cells to a CpG/Cytokine Stimulus In Vitro

    PubMed Central

    Vásquez, Camilo; Franco, Manuel A.; Angel, Juana

    2015-01-01

    Circulating human IgM expressing memory B cells have been incompletely characterized. Here, we compared the phenotype and in vitro functional response (capacity to proliferate and differentiate to antibody secreting cells) in response to CpG and a cytokine cocktail (IL-2, IL-6, and IL-10) of sorted naïve B cells, IgM memory B cells and isotype-switched circulating memory B cells. Compared to naïve B cells, IgM memory B cells had lower integrated mean fluorescence intensity (iMFI) of BAFF-R, CD38, CD73, and IL-21R, but higher iMFI of CD95, CD11c, TLR9, PD-1, and CD122. Compared to switched memory B cells, IgM memory B cells had higher iMFI of BAFF-R, PD-1, IL-21R, TLR9, and CD122, but lower iMFI of CD38, CD95, and CD73. Four days after receiving the CpG/cytokine cocktail, higher frequencies of IgM than switched memory B cells—and these in turn greater than naïve cells—proliferated and differentiated to antibody secreting cells. At this time point, a small percentage (median of 7.6%) of stimulated IgM memory B cells changed isotype to IgG. Thus, among the heterogeneous population of human circulating IgM memory B cells a subset is capable of a rapid functional response to a CpG/cytokine stimulus in vitro. PMID:26439739

  14. Genetic Resistance to Malaria Is Associated With Greater Enhancement of Immunoglobulin (Ig)M Than IgG Responses to a Broad Array of Plasmodium falciparum Antigens

    PubMed Central

    Arama, Charles; Skinner, Jeff; Doumtabe, Didier; Portugal, Silvia; Tran, Tuan M.; Jain, Aarti; Traore, Boubacar; Doumbo, Ogobara K.; Davies, David Huw; Troye-Blomberg, Marita; Dolo, Amagana; Felgner, Philip L.; Crompton, Peter D.

    2015-01-01

    Background.?People of the Fulani ethnic group are more resistant to malaria compared with genetically distinct ethnic groups, such as the Dogon people, in West Africa, and studies suggest that this resistance is mediated by enhanced antibody responses to Plasmodium falciparum antigens. However, prior studies measured antibody responses to <0.1% of P falciparum proteins, so whether the Fulani mount an enhanced and broadly reactive immunoglobulin (Ig)M and IgG response to P falciparum remains unknown. In general, little is known about the extent to which host genetics influence the overall antigen specificity of IgM and IgG responses to natural infections. Methods.?In a cross-sectional study in Mali, we collected plasma from asymptomatic, age-matched Fulani (n = 24) and Dogon (n = 22) adults with or without concurrent P falciparum infection. We probed plasma against a protein microarray containing 1087 P falciparum antigens and compared IgM and IgG profiles by ethnicity. Results.?We found that the breadth and magnitude of P falciparum-specific IgM and IgG responses were significantly higher in the malaria-resistant Fulani versus the malaria-susceptible Dogon, and, unexpectedly, P falciparum-specific IgM responses more strongly distinguished the 2 ethnic groups. Conclusions.?These findings point to an underappreciated role for IgM in protection from malaria, and they suggest that host genetics may influence the antigen specificity of IgM and IgG responses to infection. PMID:26361633

  15. Diagnostic accuracy of an IgM enzyme-linked immunosorbent assay and comparison with 2 polymerase chain reactions for early diagnosis of human leptospirosis.

    PubMed

    Vanasco, N B; Jacob, P; Landolt, N; Chiani, Y; Schmeling, M F; Cudos, C; Tarabla, H; Lottersberger, J

    2016-04-01

    Enzyme-linked immunosorbent assay (ELISA) tests and polymerase chain reaction (PCR) may play a key role for early detection and treatment of human leptospirosis in developing countries. The aims of this study were to develop and validate an IgM ELISA under field conditions and to compare the diagnostic accuracy among IgG, IgM ELISAs, conventional PCR (cPCR), and real-time PCR (rtPCR) for early detection of human leptospirosis. Overall accuracy of IgM ELISA was sensitivity of 87.9%, specificity of 97.0%, and area under the curve of 0.940. When the 4 methods were compared, IgM ELISA showed the greatest diagnostic accuracy (J=0.6) followed by rtPCR (J=0.4), cPCR (J=0.2) and IgG ELISA (J=0.1). Our results support the use of IgM ELISA and rtPCR for early diagnosis of the disease. Moreover, due to their high specificity, they could be also useful to replace or supplement microscopic agglutination test as a confirmatory test, allowing more confirmations. PMID:26867967

  16. IFN-γ-producing CD4+ T cells promote generation of protective germinal center-derived IgM+ B cell memory against Salmonella Typhi.

    PubMed

    Perez-Shibayama, Christian; Gil-Cruz, Cristina; Pastelin-Palacios, Rodolfo; Cervantes-Barragan, Luisa; Hisaki, Emiliano; Chai, Qian; Onder, Lucas; Scandella, Elke; Regen, Tommy; Waisman, Ari; Isibasi, Armando; Lopez-Macias, Constantino; Ludewig, Burkhard

    2014-06-01

    Abs play a significant role in protection against the intracellular bacterium Salmonella Typhi. In this article, we investigated how long-term protective IgM responses can be elicited by a S. Typhi outer-membrane protein C- and F-based subunit vaccine (porins). We found that repeated Ag exposure promoted a CD4(+) T cell-dependent germinal center reaction that generated mutated IgM-producing B cells and was accompanied by a strong expansion of IFN-γ-secreting T follicular helper cells. Genetic ablation of individual cytokine receptors revealed that both IFN-γ and IL-17 are required for optimal germinal center reactions and production of porin-specific memory IgM(+) B cells. However, more profound reduction of porin-specific IgM B cell responses in the absence of IFN-γR signaling indicated that this cytokine plays a dominant role. Importantly, mutated IgM mAbs against porins exhibited bactericidal capacity and efficiently augmented S. Typhi clearance. In conclusion, repeated vaccination with S. Typhi porins programs type I T follicular helper cell responses that contribute to the diversification of B cell memory and promote the generation of protective IgM Abs. PMID:24778443

  17. [IgM antibody detection in acute viral diseases, 1995-2004: analysis of data collected at a commercial diagnostic laboratory in Japan].

    PubMed

    Ban, Fumihiko; Itabashi, Yoshinori; Masui, Yukio; Inouye, Sakae

    2007-07-01

    We analyzed data from tests for virus-specific IgM in 376,000 serum specimens sent to a commercial diagnostic laboratory from clinics nationwide between 1995 and 2004. IgM antibodies to measles, rubella, mumps, parvo B19, and varicella-zoster viruses were tested using IgM-capture ELISA kits. Among specimens, 254,000 (68%) had documentation of age, of which 56% were sera from persons<20 and 44%> or = 20 years of age. Monthly or yearly trends in IgM antibody-positive tests in<20 year-old persons were similar to those in pediatric patients per sentinel clinic reported by the National Epidemiological Surveillance of Infectious Diseases (NESID), which collects weekly numbers of patients with designated infectious diseases from 3000 pediatrics clinics nationwide. Patterns of changes in monthly IgM positive tests in both < 20 and > or = 20 y specimens were similar, indicating that infections occur simultaneously in both children and adults. Adult IgM-positive specimens came from internal medicine clinics and from dermatology clinics for measles; from dermatology and obstetrics clinics for rubella and parvo B19; from otolaryngology clinics for mumps; and from dermatology and otolaryngology clinics for varicella-zoster virus. Analysis of large numbers of IgM test results at regular intervals may contribute to understanding of the epidemiology of these viral diseases in Japan. PMID:17695798

  18. Transferrin-immune complex disease: a potentially overlooked gammopathy mediated by IgM and IgG.

    PubMed

    Forni, Gian Luca; Pinto, Valeria; Musso, Marco; Mori, Marco; Girelli, Domenico; Caldarelli, Ilaria; Borriello, Adriana; Ragione, Fulvio Della

    2013-12-01

    The combination of marked hypersideremia, hypertransferrinemia, and monoclonal gammopathy of underdetermined significance (MGUS) should alert clinicians to the possible presence of an anti-transferrin immunoglobulin, an uncommon acquired disorder also defined as transferrin-immune complex disease (TICD). The authors have previously described a case of TICD with 100% transferrin saturation and liver iron overload. However, the findings in the few cases so far reported are heterogeneous, and the presence of high transferrin saturation and liver iron overload is not universal. In this article, the authors have described the identification of two additional patients with anti-transferrin monoclonal gammopathy, hypersideremia, and hypertransferrinemia, but with incomplete transferrin saturation and no hepatic iron overload. The autoantibodies were purified by using transferrin as affinity bait and characterized. One subject showed a high-titer monoclonal anti-transferrin IgM with a ?-type light chain. This finding is the first observation of IgM autoantibodies against transferrin. The other patient developed the disease after pregnancy. In this study, monoclonal antibody was an IgG mounting a ?-type light chain with altered molecular weight. These results highlight that transferrin might induce the development of a monoclonal immune response of different classes and specificity. The identification, in a single hematologic center, of three different subjects with anti-transferrin monoclonal gammopathy suggests that the disease probably represents a still underdiagnosed condition. From a clinical standpoint, these patients must be followed up both as MGUS and as hemochromatosis. PMID:23913829

  19. The BOSS DR9 Lyman-alpha Forest Sample and Constraints on the IGM Temperature-Density Relation

    NASA Astrophysics Data System (ADS)

    Lee, Khee-Gan

    2013-01-01

    We present the Lyman-alpha Forest Sample from BOSS DR9 comprising 55,305 quasars at z>2.15, with Lyman-alpha forest coverage. This sample also includes a set of products designed to aid in Lyman-alpha forest analysis, such as quasar continua accurate to <5% RMS, simplified pixel masks (to account for DLA cores, strong sky lines, and intervening metal absorbers), DLA damping wing corrections, and pipeline noise corrections. We also discuss an effort to measure the flux transmission probability distribution function (PDF) of the Lyman-alpha forest from BOSS. This requires detailed modeling of the resolution, continuum and noise properties of the BOSS spectra. We describe a new probabilistic method to model the noise properties of the BOSS data which allows us to separate the photon-counting and CCD noise components in each spectrum. Comparing with mock spectra generated from hydrodynamical simulations of the intergalactic medium (IGM), we place constraints on the evolution of the IGM temperature-density relation from 2.15 < z < 3.15.

  20. Prevalence of Legionella-specific IgG and IgM antibody in a dental clinic population.

    PubMed

    Fotos, P G; Westfall, H N; Snyder, I S; Miller, R W; Mutchler, B M

    1985-12-01

    This study was undertaken to determine the frequency of Legionella infection in a dental clinic setting. Serum samples from 270 dental clinic personnel were evaluated using an enzyme-linked immunosorbent assay to detect Legionella-specific IgM and IgG antibodies. The pooled-species whole-cell-antigen preparation used in these assays was derived from six Legionella pneumophila strains and one strain each from Legionella bozemanii and Legionella micdadei. Significant levels of IgG and IgM antibodies were found in 20% and 16%, respectively, of the samples. This compares with 8% and 10%, respectively, for a randomly selected non-clinical group from the region (P less than 0.005). Samples from clinic personnel with significant IgG titers (greater than 1:128) were also evaluated for activity to each of the eight single-species antigens, with the following results: L. pneumophila, 45% (combined six strains); L. micdadei, 37%; and L. bozemanii, 18%. Comparing individuals' "years spent in the clinic environment" with the incidence of significant antibody levels strongly suggests that the risk of Legionella infection increases proportionately with increased clinic exposure time (P less than 0.05). Analysis of these data implies that Legionella may be present in the dental clinic environment, thus creating an increased risk for clinical personnel or patients. PMID:3865949

  1. Differential diagnosis of IgM MGUS and WM according to B-lymphoid infiltration by morphology and flow cytometry.

    PubMed

    Ocio, Enrique M; del Carpio, Daniel; Caballero, lvaro; Alonso, Jennifer; Paiva, Bruno; Pesoa, Roberto; Villaescusa, Teresa; Lpez-Anglada, Luca; Vidriales, Beln; Garca-Sanz, Ramn

    2011-02-01

    The distinction between IgM monoclonal gammopathy of undetermined significance (MGUS), asymptomatic Waldenstrom's macroglobulinemia (WM; aWM), and symptomatic WM (sWM) relies on two features: the presence of infiltration by lymphoplasmacytic lymphoma in the bone marrow (BM) biopsy and the existence of signs or symptoms attributable to the disease. Nevertheless, some patients lack a BM biopsy or it is not conclusive for diagnosis. In this study we have investigated 94 patients with IgM monoclonal gammopathies, in which a BM trephine biopsy and morphological and flow cytometry (FCM) evaluation of BM aspirate were available at diagnosis. We found a clear correlation between BM infiltration of B-lymphocytes assessed by morphology and by FCM with a Pearson correlation of 0.62 (P<.001). Moreover, in the absence of a BM trephine biopsy, the cut-off points that would help in the differential diagnosis between MGUS, aWM, and sWM would be 20% for morphology and 5% for FCM, both assessed in the BM aspirate. PMID:21454201

  2. A natural human IgM that binds to gangliosides is therapeutic in murine models of amyotrophic lateral sclerosis

    PubMed Central

    Xu, Xiaohua; Denic, Aleksandar; Jordan, Luke R.; Wittenberg, Nathan J.; Warrington, Arthur E.; Wootla, Bharath; Papke, Louisa M.; Zoecklein, Laurie J.; Yoo, Daehan; Shaver, Jonah; Oh, Sang-Hyun; Pease, Larry R.; Rodriguez, Moses

    2015-01-01

    ABSTRACT Amyotrophic lateral sclerosis (ALS) is a devastating, fatal neurological disease that primarily affects spinal cord anterior horn cells and their axons for which there is no treatment. Here we report the use of a recombinant natural human IgM that binds to the surface of neurons and supports neurite extension, rHIgM12, as a therapeutic strategy in murine models of human ALS. A single 200?g intraperitoneal dose of rHIgM12 increases survival in two independent genetic-based mutant SOD1 mouse strains (SOD1G86R and SOD1G93A) by 8 and 10?days, delays the onset of neurological deficits by 16?days, delays the onset of weight loss by 5?days, and preserves spinal cord axons and anterior horn neurons. Immuno-overlay of thin layer chromatography and surface plasmon resonance show that rHIgM12 binds with high affinity to the complex gangliosides GD1a and GT1b. Addition of rHIgM12 to neurons in culture increases ?-tubulin tyrosination levels, suggesting an alteration of microtubule dynamics. We previously reported that a single peripheral dose of rHIgM12 preserved neurological function in a murine model of demyelination with axon loss. Because rHIgM12 improves three different models of neurological disease, we propose that the IgM might act late in the cascade of neuronal stress and/or death by a broad mechanism. PMID:26035393

  3. Low molecular weight IgM in sera of children following bone marrow transplantation for severe aplastic anaemia and acute leukaemia.

    PubMed Central

    Jol-vd Zijde, C M; Vossen, J M; Weijden-Ragas, R V; Radl, J

    1983-01-01

    Serum samples of 16 children, treated with allogeneic bone marrow grafts for either aplastic anaemia or leukaemia, were investigated longitudinally for the presence of pentameric (19S) and low molecular weight (LMW) (7S) IgM. From 2 months following grafting, serum IgM increased in all patients, gradually in seven cases and with a transient overshoot in the other nine. In eight patients, LMW-IgM was detected transiently in the serum within the period when total IgM was increasing, either with (five patients) or without (three patients) overshoot. These data indicate that, at a certain stage of the immunological reconstitution after transplantation as in normal ontogeny, rather immature cells of the B cell lineage are able to produce and secrete LMW-IgM. PMID:6347475

  4. Reduced IgG anti-small nuclear ribonucleoprotein autoantibody production in systemic lupus erythematosus patients with positive IgM anti-cytomegalovirus antibodies

    PubMed Central

    Palafox Sánchez, Claudia Azucena; Satoh, Minoru; Chan, Edward KL; Carcamo, Wendy C; Muñoz Valle, José Francisco; Orozco Barocio, Gerardo; Oregon Romero, Edith; Navarro Hernández, Rosa Elena; Salazar Páramo, Mario; Cabral Castañeda, Antonio; Vázquez del Mercado, Mónica

    2009-01-01

    Introduction Systemic lupus erythematosus is characterized by production of autoantibodies to RNA or DNA–protein complexes such as small nuclear ribonucleoproteins (snRNPs). A role of Epstein–Barr virus in the pathogenesis has been suggested. Similar to Epstein–Barr virus, cytomegalovirus (CMV) infects the majority of individuals at a young age and establishes latency with a potential for reactivation. Homology of CMV glycoprotein B (UL55) with the U1snRNP-70 kDa protein (U1–70 k) has been described; however, the role of CMV infection in production of anti-snRNPs is controversial. We investigated the association of CMV serology and autoantibodies in systemic lupus erythematosus. Methods Sixty-one Mexican patients with systemic lupus erythematosus were tested for CMV and Epstein–Barr virus serology (viral capsid antigen, IgG, IgM) and autoantibodies by immunoprecipitation and ELISA (IgG and IgM class, U1RNP/Sm, U1–70 k, P peptide, rheumatoid factor, dsDNA, β2-glycoprotein I). Results IgG anti-CMV and IgM anti-CMV were positive in 95% (58/61) and 33% (20/61), respectively, and two cases were negative for both. Clinical manifestation and autoantibodies in the IgM anti-CMV(+) group (n = 20) versus the IgM anti-CMV(-)IgG (+) (n = 39) group were compared. Most (19/20) of the IgM anti-CMV(+) cases were IgG anti-CMV(+), consistent with reactivation or reinfection. IgM anti-CMV was unrelated to rheumatoid factor or IgM class autoantibodies and none was positive for IgM anti-Epstein–Barr virus–viral capsid antigen, indicating that this is not simply due to false positive results caused by rheumatoid factor or nonspecific binding by certain IgM. The IgM anti-CMV(+) group has significantly lower levels of IgG anti-U1RNP/Sm and IgG anti-U1–70 k (P = 0.0004 and P = 0.0046, respectively). This finding was also confirmed by immunoprecipitation. Among the IgM anti-CMV(-) subset, anti-Su was associated with anti-U1RNP and anti-Ro (P < 0.05). High levels of IgG anti-CMV were associated with production of lupus-related autoantibodies to RNA or DNA–protein complex (P = 0.0077). Conclusions Our findings suggest a potential role of CMV in regulation of autoantibodies to snRNPs and may provide a unique insight to understand the pathogenesis. PMID:19232124

  5. Laboratory diagnosis of Mycoplasma pneumoniae infection. 3. Detection of IgM antibodies to M. pneumoniae by a modified indirect haemagglutination test.

    PubMed Central

    Kok, T. W.; Marmion, B. P.; Varkanis, G.; Worswick, D. A.; Martin, J.

    1989-01-01

    The indirect haemagglutination (IHA) test was compared with the complement-fixation (CF) test for the measurement of antibodies to Mycoplasma pneumoniae. A modification of the IHA was used to measure M. pneumoniae IgM antibodies. Sera were obtained from various groups of patients who were either culture or antigen positive for M. pneumoniae in nasopharyngeal aspirates or who had fourfold or greater increase in CF antibody or a titre greater than or equal to 320. The results of these comparisons showed that the modified IHA test was specific and more sensitive (89% as opposed to 64%) than the CF test. The modified IHA test for the detection of IgM antibody was highly effective in the recognition of recent or current infection with the mycoplasma. It was also of equal sensitivity to an indirect enzyme immunoassay for the detection of IgM antibodies to M. pneumoniae. Images Fig. 1 PMID:2514114

  6. Evaluation of Commercially Available Diagnostic Tests for the Detection of Dengue Virus NS1 Antigen and Anti-Dengue Virus IgM Antibody

    PubMed Central

    Hunsperger, Elizabeth A.; Yoksan, Sutee; Buchy, Philippe; Nguyen, Vinh Chau; Sekaran, Shamala Devi; Enria, Delia A.; Vazquez, Susana; Cartozian, Elizabeth; Pelegrino, Jose L.; Artsob, Harvey; Guzman, Maria G.; Olliaro, Piero; Zwang, Julien; Guillerm, Martine; Kliks, Susie; Halstead, Scott; Peeling, Rosanna W.; Margolis, Harold S.

    2014-01-01

    Commercially available diagnostic test kits for detection of dengue virus (DENV) non-structural protein 1 (NS1) and anti-DENV IgM were evaluated for their sensitivity and specificity and other performance characteristics by a diagnostic laboratory network developed by World Health Organization (WHO), the UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR) and the Pediatric Dengue Vaccine Initiative (PDVI). Each network laboratory contributed characterized serum specimens for the panels used in the evaluation. Microplate enzyme-linked immunosorbent assay (ELISA) and rapid diagnostic test (RDT formats) were represented by the kits. Each ELISA was evaluated by 2 laboratories and RDTs were evaluated by at least 3 laboratories. The reference tests for IgM anti-DENV were laboratory developed assays produced by the Armed Forces Research Institute for Medical Science (AFRIMS) and the Centers for Disease Control and Prevention (CDC), and the NS1 reference test was reverse transcriptase polymerase chain reaction (RT-PCR). Results were analyzed to determine sensitivity, specificity, inter-laboratory and inter-reader agreement, lot-to-lot variation and ease-of-use. NS1 ELISA sensitivity was 60–75% and specificity 71–80%; NS1 RDT sensitivity was 38–71% and specificity 76–80%; the IgM anti-DENV RDTs sensitivity was 30–96%, with a specificity of 86–92%, and IgM anti-DENV ELISA sensitivity was 96–98% and specificity 78–91%. NS1 tests were generally more sensitive in specimens from the acute phase of dengue and in primary DENV infection, whereas IgM anti-DENV tests were less sensitive in secondary DENV infections. The reproducibility of the NS1 RDTs ranged from 92-99% and the IgM anti-DENV RDTs from 88–94%. PMID:25330157

  7. The role of B-cells and IgM antibodies in parasitemia, anemia, and VSG switching in Trypanosoma brucei-infected mice.

    PubMed

    Magez, Stefan; Schwegmann, Anita; Atkinson, Robert; Claes, Filip; Drennan, Michael; De Baetselier, Patrick; Brombacher, Frank

    2008-01-01

    African trypanosomes are extracellular parasitic protozoa, predominantly transmitted by the bite of the haematophagic tsetse fly. The main mechanism considered to mediate parasitemia control in a mammalian host is the continuous interaction between antibodies and the parasite surface, covered by variant-specific surface glycoproteins. Early experimental studies have shown that B-cell responses can be strongly protective but are limited by their VSG-specificity. We have used B-cell (microMT) and IgM-deficient (IgM(-/-)) mice to investigate the role of B-cells and IgM antibodies in parasitemia control and the in vivo induction of trypanosomiasis-associated anemia. These infection studies revealed that that the initial setting of peak levels of parasitemia in Trypanosoma brucei-infected microMT and IgM(-/-) mice occurred independent of the presence of B-cells. However, B-cells helped to periodically reduce circulating parasites levels and were required for long term survival, while IgM antibodies played only a limited role in this process. Infection-associated anemia, hypothesized to be mediated by B-cell responses, was induced during infection in microMT mice as well as in IgM(-/-) mice, and as such occurred independently from the infection-induced host antibody response. Antigenic variation, the main immune evasion mechanism of African trypanosomes, occurred independently from host antibody responses against the parasite's ever-changing antigenic glycoprotein coat. Collectively, these results demonstrated that in murine experimental T. brucei trypanosomiasis, B-cells were crucial for periodic peak parasitemia clearance, whereas parasite-induced IgM antibodies played only a limited role in the outcome of the infection. PMID:18688274

  8. Multiple Plasmodium falciparum Erythrocyte Membrane Protein 1 Variants per Genome Can Bind IgM via Its Fc Fragment Fcμ

    PubMed Central

    Jeppesen, Anine; Ditlev, Sisse Bolm; Soroka, Vladyslav; Stevenson, Liz; Turner, Louise; Dzikowski, Ron; Hviid, Lars

    2015-01-01

    The Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) adhesive proteins expressed on the surfaces of infected erythrocytes (IEs) are of key importance in the pathogenesis of P. falciparum malaria. Several structurally and functionally defined PfEMP1 types have been associated with severe clinical manifestations, such as cerebral malaria in children and placental malaria in pregnant women. PfEMP1 that can bind the Fc part of IgM (Fcμ) characterizes one such type, although the functional significance of this IgM binding to PfEMP1 remains unclear. In this study, we report the identification and functional analysis of five IgM-binding PfEMP1 proteins encoded by P. falciparum NF54. In addition to the VAR2CSA-type PFL0030c protein, already known to bind Fcμ and to mediate chondroitin sulfate A (CSA)-specific adhesion of IEs in the placenta, we found four PfEMP1 proteins not previously known to bind IgM this way. Although they all contained Duffy binding-like ε (DBLε) domains similar to those in VAR2CSA-type PfEMP1, they did not mediate IE adhesion to CSA, and IgM binding did not shield IEs from phagocytosis of IgG-opsonized IEs. In this way, these new IgM-binding PfEMP1 proteins resemble the rosette-mediating and IgM-binding PfEMP1 HB3VAR06, but none of them mediated formation of rosettes. We could map the capacity for Fc-specific IgM binding to DBLε domains near the C terminus for three of the four PfEMP1 proteins tested. Our study provides new evidence regarding Fc-dependent binding of IgM to PfEMP1, which appears to be a common and multifunctional phenotype. PMID:26216422

  9. Detection of IgM antibodies against canine distemper virus in dog and mink sera employing enzyme-linked immunosorbent assay (ELISA).

    PubMed

    Blixenkrone-Mller, M; Pedersen, I R; Appel, M J; Griot, C

    1991-01-01

    An enzyme-linked immunosorbent assay (ELISA) for the detection of IgM antibodies against canine distemper virus (CDV) in canine and mink serum is described. The diagnostic potential of this technique was evaluated by analyzing sera from natural or experimental infections in dog and mink and negative control sera. These results were compared with results obtained in the developed CDV IgG ELISA and in the virus neutralization test. The IgM test, which requires only a single serum specimen, is a useful method for diagnosing current or recent CDV infections in dog and mink. PMID:2039785

  10. Clinicopathologic Characterization of Diffuse-Large-B-Cell Lymphoma with an Associated Serum Monoclonal IgM Component

    PubMed Central

    Scarpino, Stefania; Salerno, Gerardo; Tatarelli, Caterina; Talerico, Caterina; Lombardi, Mariangela; Monarca, Bruno; Amadori, Sergio; Ruco, Luigi

    2014-01-01

    Recently, diffuse-large-B-cell lymphoma (DLBCL) associated with serum IgM monoclonal component (MC) has been shown to be a very poor prognostic subset although, detailed pathological and molecular data are still lacking. In the present study, the clinicopathological features and survival of IgM-secreting DLBCL were analyzed and compared to non-secreting cases in a series of 151 conventional DLBCL treated with R-CHOP. IgM MC was detected in 19 (12.5%) out of 151 patients at disease onset. In 17 of these cases secretion was likely due to the neoplastic clone, as suggested by the expression of heavy chain IgM protein in the cytoplasm of tumor cells. In IgM-secreting cases immunoblastic features (p<.0001), non-GCB-type (p = .002) stage III-IV(p = .003), ≥2 extra nodal sites (p<.0001), bone-marrow (p = .002), central-nervous-system (CNS) involvement at disease onset or relapse (p<.0001), IPI-score 3–5 (p = .009) and failure to achieve complete remission (p = .005), were significantly more frequent. FISH analyses for BCL2, BCL6 and MYC gene rearrangements detected only two cases harboring BCL2 gene translocation and in one case a concomitant BCL6 gene translocation was also observed. None of the IgM-secreting DLBCL was found to have L265P mutation of MYD88 gene. Thirty-six month event-free (11.8% vs 66.4% p<.0001), progression-free (23.5% vs 75.7%, p<.0001) and overall (47.1% vs 74.8%, p<.0001) survivals were significantly worse in the IgM-secreting group. In multivariate analysis IgM-secreting (p = .005, expB = 0.339, CI = 0.160-0.716) and IPI-score 3–5 (p = .010, expB = 0.274, CI = 0.102–0.737) were the only significant factors for progression-free-survival. Notably, four relapsed patients, who were treated with salvage immmunochemotherapy combined with bortezomib or lenalidomide, achieved lasting remission. Our data suggests that IgM-secreting cases are a distinct subset of DLBCL, originating from activated-B-cells with terminally differentiated features, prevalent extra nodal dissemination and at high risk of CNS involvement. PMID:24705344

  11. Production of human monoclonal IgG and IgM antibodies with anti-D (rhesus) specificity using heterohybridomas.

    PubMed Central

    Thompson, K M; Melamed, M D; Eagle, K; Gorick, B D; Gibson, T; Holburn, A M; Hughes-Jones, N C

    1986-01-01

    Heterohybridomas secreting human IgM and IgG anti-D antibodies of the rhesus blood group system have been established by fusion of EBV-transformed anti-D secreting cells with the mouse myeloma cells X63-Ag8.653. Both classes of antibody reacted with all Rh-positive cells, some Du cells but not with Rh-negative or DB cells. Concentrations of both antibodies reached between 25 micrograms/ml and 50 micrograms/ml in the culture supernatants. The cell lines have been maintained in culture for 14 months and have been shown to be suitable for large-scale production of antibody. PMID:3011653

  12. Immune Dysfunction in Rett Syndrome Patients Revealed by High Levels of Serum Anti-N(Glc) IgM Antibody Fraction

    PubMed Central

    Papini, Anna Maria; Real-Fernandez, Feliciana; Rossi, Giada; Tiberi, Caterina; Sabatino, Giuseppina; Pandey, Shashank; Lavielle, Solange; Ciccoli, Lucia; Hayek, Joussef

    2014-01-01

    Rett syndrome (RTT), a neurodevelopmental disorder affecting exclusively (99%) female infants, is associated with loss-of-function mutations in the gene encoding methyl-CpG binding protein 2 (MECP2) and, more rarely, cyclin-dependent kinase-like 5 (CDKL5) and forkhead box protein G1 (FOXG1). In this study, we aimed to evaluate the function of the immune system by measuring serum immunoglobulins (IgG and IgM) in RTT patients (n = 53) and, by comparison, in age-matched children affected by non-RTT pervasive developmental disorders (non-RTT PDD) (n = 82) and healthy age-matched controls (n = 29). To determine immunoglobulins we used both a conventional agglutination assay and a novel ELISA based on antibody recognition by a surrogate antigen probe, CSF114(Glc), a synthetic N-glucosylated peptide. Both assays provided evidence for an increase in IgM titer, but not in IgG, in RTT patients relative to both healthy controls and non-RTT PDD patients. The significant difference in IgM titers between RTT patients and healthy subjects in the CSF114(Glc) assay (P = 0.001) suggests that this procedure specifically detects a fraction of IgM antibodies likely to be relevant for the RTT disease. These findings offer a new insight into the mechanism underlying the Rett disease as they unveil the possible involvement of the immune system in this pathology. PMID:25389532

  13. Seroprevalence of immunoglobulin M (IgM) and IgG antibodies to polysaccharides of Streptococcus pneumoniae in different age groups of Ecuadorian and German children.

    PubMed

    Brssow, H; Baensch, M; Sidoti, J

    1992-11-01

    The age-specific prevalence of serum immunoglobulin M (IgM) antibody to capsular polysaccharides of Streptococcus pneumoniae, as detected by enzyme-linked immunosorbent assay, was studied in 1,301 Ecuadorian children enrolled in a national nutrition and health survey. This prevalence was 6% in infants < 6 months old and increased to 28% in children 6 to 11 months old, 49% in those 12 to 17 months old, and 58% in those 18 to 23 months old. About 80% of the 5-year-old children had this antibody. When tested separately against six different capsular polysaccharides, serum IgM antibody reacted with decreasing frequency with serotype 3, 8, 19, 6, 23, and 1 capsular polysaccharides. We did not observe a broadening of the antibody response with increasing age in the sense that more and more serotypes were recognized. A similar age-related prevalence was found for IgM antibody to the species-specific C-polysaccharide of S. pneumoniae and for IgG antibody to capsular polysaccharides of S. pneumoniae. A smaller German serum collection showed a comparable age-related prevalence of pneumococcus-specific serum IgG and IgM antibodies. The highest incidence of respiratory diseases was observed in 1- and 2-year-old Ecuadorian children. It thus seems that acquisition of serum antibody to S. pneumoniae reflects more the developmental maturation of an immune response than an actual exposure to different pneumococcal serotypes. PMID:1452644

  14. Seroprevalence of immunoglobulin M (IgM) and IgG antibodies to polysaccharides of Streptococcus pneumoniae in different age groups of Ecuadorian and German children.

    PubMed Central

    Brssow, H; Baensch, M; Sidoti, J

    1992-01-01

    The age-specific prevalence of serum immunoglobulin M (IgM) antibody to capsular polysaccharides of Streptococcus pneumoniae, as detected by enzyme-linked immunosorbent assay, was studied in 1,301 Ecuadorian children enrolled in a national nutrition and health survey. This prevalence was 6% in infants < 6 months old and increased to 28% in children 6 to 11 months old, 49% in those 12 to 17 months old, and 58% in those 18 to 23 months old. About 80% of the 5-year-old children had this antibody. When tested separately against six different capsular polysaccharides, serum IgM antibody reacted with decreasing frequency with serotype 3, 8, 19, 6, 23, and 1 capsular polysaccharides. We did not observe a broadening of the antibody response with increasing age in the sense that more and more serotypes were recognized. A similar age-related prevalence was found for IgM antibody to the species-specific C-polysaccharide of S. pneumoniae and for IgG antibody to capsular polysaccharides of S. pneumoniae. A smaller German serum collection showed a comparable age-related prevalence of pneumococcus-specific serum IgG and IgM antibodies. The highest incidence of respiratory diseases was observed in 1- and 2-year-old Ecuadorian children. It thus seems that acquisition of serum antibody to S. pneumoniae reflects more the developmental maturation of an immune response than an actual exposure to different pneumococcal serotypes. PMID:1452644

  15. Immunohistochemical detection of IgM and IgG in lung tissue of dogs with leptospiral pulmonary haemorrhage syndrome (LPHS)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Leptospiral pulmonary haemorrhage syndrome (LPHS) is a severe form of leptospirosis. Pathogenic mechanisms are poorly understood. Lung tissues from 26 dogs with LPHS, 5 dogs with pulmonary haemorrhage due to other causes and 6 healthy lungs were labelled for IgG, IgM and leptospiral antigens. Three ...

  16. Long-term efficacy of rituximab in IgM anti-myelin-associated glycoprotein neuropathy: RIMAG follow-up study.

    PubMed

    Iancu Ferfoglia, Ruxandra; Guimarães-Costa, Raquel; Viala, Karine; Musset, Lucile; Neil, Jean; Marin, Benoit; Léger, Jean-Marc

    2016-03-01

    The Rituximab vs. Placebo in Polyneuropathy Associated With Anti-MAG IgM Monoclonal Gammopathy (RIMAG) study showed no improvement using the inflammatory neuropathy cause and treatment sensory score (ISS) as primary outcome in patients with IgM anti-myelin-associated glycoprotein neuropathy (IgM anti-MAG neuropathy) treated with rituximab, when compared with placebo. However, some secondary outcomes seemed to improve in the per protocol analysis. Patients from one participating center in the RIMAG study underwent a new evaluation after a median follow-up of 6 (interquartile range (IQR) 4.9; 6.5) years, using the same outcome measures used in the original study. Data were recorded in seven rituximab patients (group 1) and in eight placebo patients (group 2). In group 2, six of eight patients received immunotherapy during follow-up, while only two of seven did in group 1. No significant change was observed in either the ISS or the secondary outcomes in both groups, with the exception of worsening in the 10-m walk time in group 2 (p = 0.016). The RIMAG follow-up study failed to find any significant change in most outcome measures in patients from the RIMAG study, some of them having received new immunotherapies. This study stresses the lack of useful clinical scales sensitive enough to capture small, even meaningful, improvement in IgM anti-MAG neuropathy. PMID:26748872

  17. Diagnostic Accuracy of Recombinant Immunoglobulin-like Protein A-Based IgM ELISA for the Early Diagnosis of Leptospirosis in the Philippines

    PubMed Central

    Kitashoji, Emi; Koizumi, Nobuo; Lacuesta, Talitha Lea V.; Usuda, Daisuke; Ribo, Maricel R.; Tria, Edith S.; Go, Winston S.; Kojiro, Maiko; Parry, Christopher M.; Dimaano, Efren M.; Villarama, Jose B.; Ohnishi, Makoto; Suzuki, Motoi; Ariyoshi, Koya

    2015-01-01

    Background Leptospirosis is an important but largely under-recognized public health problem in the tropics. Establishment of highly sensitive and specific laboratory diagnosis is essential to reveal the magnitude of problem and to improve treatment. This study aimed to evaluate the diagnostic accuracy of a recombinant LigA protein based IgM ELISA during outbreaks in the clinical-setting of a highly endemic country. Methodology/Principal Findings A prospective study was conducted from October 2011 to September 2013 at a national referral hospital for infectious diseases in Manila, Philippines. Patients who were hospitalized with clinically suspected leptospirosis were enrolled. Plasma and urine were collected on admission and/or at discharge and tested using the LigA-IgM ELISA and a whole cell-based IgM ELISA. Sensitivity and specificity of these tests were evaluated with cases diagnosed by microscopic agglutination test (MAT), culture and LAMP as the composite reference standard and blood bank donors as healthy controls: the mean+3 standard deviation optical density value of healthy controls was used as the cut-off limit (0.062 for the LigA-IgM ELISA and 0.691 for the whole cell-based IgM ELISA). Of 304 patients enrolled in the study, 270 (89.1%) were male and the median age was 30.5 years; 167 (54.9%) were laboratory confirmed. The sensitivity and ROC curve AUC for the LigA-IgM ELISA was significantly greater than the whole cell-based IgM ELISA (69.5% vs. 54.3%, p<0.01; 0.90 vs. 0.82, p<0.01) on admission, but not at discharge. The specificity of LigA-IgM ELISA and whole cell-based IgM ELISA were not significantly different (98% vs. 97%). Among 158 MAT negative patients, 53 and 28 were positive by LigA- and whole cell-based IgM ELISA, respectively; if the laboratory confirmation was re-defined by LigA-IgM ELISA and LAMP, the clinical findings were more characteristic of leptospirosis than the diagnosis based on MAT/culture/LAMP. Conclusions/Significance The newly developed LigA-IgM ELISA is more sensitive than the whole cell-based IgM based ELISA. Although the final diagnosis must be validated by more specific tests, LigA-IgM ELISA could be a useful diagnostic test in a real clinical-setting, where diagnosis is needed in the early phase of infection. PMID:26110604

  18. In Vivo-Expressed Proteins of Virulent Leptospira interrogans Serovar Autumnalis N2 Elicit Strong IgM Responses of Value in Conclusive Diagnosis.

    PubMed

    Raja, Veerapandian; Shanmughapriya, Santhanam; Kanagavel, Murugesan; Artiushin, Sergey C; Velineni, Sridhar; Timoney, John F; Natarajaseenivasan, Kalimuthusamy

    2015-01-01

    Leptospirosis is a serious zoonosis that is underdiagnosed because of limited access to laboratory facilities in Southeast Asia, Central and South America, and Oceania. Timely diagnosis of locally distributed serovars of high virulence is crucial for successful care and outbreak management. Using pooled patient sera, an expression gene library of a virulent Leptospira interrogans serovar Autumnalis strain N2 isolated in South India was screened. The identified genes were characterized, and the purified recombinant proteins were used as antigens in IgM enzyme-linked immunosorbent assay (ELISA) either singly or in combination. Sera (n = 118) from cases of acute leptospirosis along with sera (n = 58) from healthy subjects were tested for reactivity with the identified proteins in an ELISA designed to detect specific IgM responses. We have identified nine immunoreactive proteins, ArgC, RecA, GlpF, FliD, TrmD, RplS, RnhB, Lp28.6, and Lrr44.9, which were found to be highly conserved among pathogenic leptospires. Apparently, the proteins ArgC, RecA, GlpF, FliD, TrmD, and Lrr44.9 are expressed during natural infection of the host and undetectable in in vitro cultures. Among all the recombinant proteins used as antigens in IgM ELISA, ArgC had the highest sensitivity and specificity, 89.8% and 95.5%, respectively, for the conclusive diagnosis of leptospirosis. The use of ArgC and RecA in combination for IgM ELISA increased the sensitivity and specificity to 95.7% and 94.9%, respectively. ArgC and RecA thus elicited specific IgM responses and were therefore effective in laboratory confirmation of Leptospira infection. PMID:26607308

  19. Reconstituted Human Polyclonal Plasma-derived Secretory-like IgM and IgA Maintain the Barrier Function of Epithelial Cells Infected with an Enteropathogen*

    PubMed Central

    Longet, Stéphanie; Vonarburg, Cédric; Lötscher, Marius; Miescher, Sylvia; Zuercher, Adrian; Corthésy, Blaise

    2014-01-01

    Intravenous administration of polyclonal and monoclonal antibodies has proven to be a clinically valid approach in the treatment, or at least relief, of many acute and chronic pathologies, such as infection, immunodeficiency, and a broad range of autoimmune conditions. Plasma-derived IgG or recombinant IgG are most frequently used for intravenous or subcutaneous administration, whereas a few IgM-based products are available as well. We have established recently that secretory-like IgA and IgM can be produced upon association of plasma-derived polymeric IgA and IgM with a recombinant secretory component. As a next step toward potential future mucosal administration, we sought to unravel the mechanisms by which these secretory Igs protect epithelial cells located at the interface between the environment and the inside of the body. By using polarized epithelial Caco-2 cell monolayers and Shigella flexneri as a model enteropathogen, we found that polyspecific plasma-derived SIgA and SIgM fulfill many protective functions, including dose-dependent recognition of the antigen via formation of aggregated immune complexes, reduction of bacterial infectivity, maintenance of epithelial cell integrity, and inhibition of proinflammatory cytokine/chemokine production by epithelial cells. In this in vitro model devoid of other cellular or molecular interfering partners, IgM and secretory IgM showed stronger bacterial neutralization than secretory IgA. Together, these data suggest that mucosally delivered antibody preparations may be most effective when combining both secretory-like IgA and IgM, which, together, play a crucial role in preserving several levels of epithelial cell integrity. PMID:24951593

  20. Pre-cut Filter Paper for Detecting Anti-Japanese Encephalitis Virus IgM from Dried Cerebrospinal Fluid Spots

    PubMed Central

    Bharucha, Tehmina; Chanthongthip, Anisone; Phuangpanom, Soumphou; Phonemixay, Ooyanong; Sengvilaipaseuth, Onanong; Vongsouvath, Manivanh; Lee, Sue; Newton, Paul N.; Dubot-Pérès, Audrey

    2016-01-01

    Background The use of filter paper as a simple, inexpensive tool for storage and transportation of blood, ‘Dried Blood Spots’ or Guthrie cards, for diagnostic assays is well-established. In contrast, there are a paucity of diagnostic evaluations of dried cerebrospinal fluid (CSF) spots. These have potential applications in low-resource settings, such as Laos, where laboratory facilities for central nervous system (CNS) diagnostics are only available in Vientiane. In Laos, a major cause of CNS infection is Japanese encephalitis virus (JEV). We aimed to develop a dried CSF spot protocol and to evaluate its diagnostic performance using the World Health Organisation recommended anti-JEV IgM antibody capture enzyme-linked immunosorbent assay (JEV MAC-ELISA). Methodology and Principal Findings Sample volumes, spotting techniques and filter paper type were evaluated using a CSF-substitute of anti-JEV IgM positive serum diluted in Phosphate Buffer Solution (PBS) to end-limits of detection by JEV MAC-ELISA. A conventional protocol, involving eluting one paper punch in 200μl PBS, did not detect the end-dilution, nor did multiple punches utilising diverse spotting techniques. However, pre-cut filter paper enabled saturation with five times the volume of CSF-substitute, sufficiently improving sensitivity to detect the end-dilution. The diagnostic accuracy of this optimised protocol was compared with routine, neat CSF in a pilot, retrospective study of JEV MAC-ELISA on consecutive CSF samples, collected 2009–15, from three Lao hospitals. In comparison to neat CSF, 132 CSF samples stored as dried CSF spots for one month at 25–30°C showed 81.6% (65.7–92.3 95%CI) positive agreement, 96.8% (91.0–99.3 95%CI) negative agreement, with a kappa coefficient of 0.81 (0.70–0.92 95%CI). Conclusions/Significance The novel design of pre-cut filter paper saturated with CSF could provide a useful tool for JEV diagnostics in settings with limited laboratory access. It has the potential to improve national JEV surveillance and inform vaccination policies. The saturation of filter paper has potential use in the wider context of pathogen detection, including dried spots for detecting other analytes in CSF, and other body fluids. PMID:26986061

  1. The importance of quaternary structure in the expression of the C1-binding site of IgM.

    PubMed Central

    Bubb, M O; Conradie, J D

    1976-01-01

    The ability of C1 to bind to the Fc5mu-fragment of a monoclonal IgM was determined by means of a haemolytic C1-inhibition assay. Fc5mu fragments were produced by trypsin digestion at five different temperatures ranging from 54-62 degrees (2 degrees increments) and were purified by immunoadsorption through a column of monospecific anti-Fabmu and by molecular exclusion chromatography. Analytical ultracentrifugation showed the final preparations to be free of aggregates. A plot of mug Fc5mu required to inhibit 50% of available C1 versus temperatures of production of the fragment yielded a curve with a minimum at 58-60 degrees. Upon mild reduction and alkylation of these Fc5mu fragments their C1-fixing capacity became approximately the same irrespective of temperature of production. Fc5mu was also prepared at 25 degrees in the presence of 5 M urea, purified by immunoadsorption as before and aliquots then exposed to temperatures ranging from 40-70 degrees (5 degrees increments) for 15 min. After aggregates had been removed by chromatography a similar minimum in C1-fixation was again observed at 60 degrees. Reduction and alkylation once more abolished these differences. Fc5mu and its reduced and alkylated subunits, produced at 60 degrees and then exposed to various concentrations of urea (0-7 M) for 24 hd did not yield a minimum in C1 fixation. Reduced and alkylated Fcmu incubated at various temperatures (40-70 degrees) also did not fix C1 differentially. Examination in the near and far u.v. region of the circular dichroism spectra of different Fc5mu preparations showed a gradual loss of structure associated with restricted aromatic chromophores and secondary (beta) structure with increased temperature. Urea denaturation had a more pronounced and irreversible effect on Fc5 mu conformation. These changes could not be correlated with the CU-fixation patterns observed. It would therefore appear that elevated temperatures induce a static change in the pentameric FC-part of IgM which in turn directly influences or modulates the availability of the C1-binding site. The importance of disulphide bonds in maintaining these temperature-induced changes in Fc5mu was also indicated. Images Figure 2 Figure 3 Figure 4 Figure 5 PMID:825451

  2. Seeing the Lyman-Alpha Forest for the Trees: Constraints on the Thermal State of the IGM from SDSS-III/BOSS

    NASA Astrophysics Data System (ADS)

    Lee, Khee-Gan

    The Lyman-alpha (Lya) forest in the line-of-sight to distant quasars is an important probe of the intergalactic medium (IGM). The thermal properties of the IGM can provide insight the reionization history of the universe, as well as indirectly constraining energy sources in the universe such as galaxies and quasars. This thesis is concerned primarily with studying the IGM using moderate quality Lya forest data sets from large-scale spectroscopic surveys, such as the Sloan Digital Sky Survey (SDSS) and the Baryon Oscillations Spectroscopic Survey (BOSS). In Chapter 1, we study the potential of SDSS Lya forest data to study the IGM. Using simulated mock spectra, we show that the flux probability distribution function (PDF) of SDSS data can place interesting constraints on the spatially-averaged temperature-density relation (TDR) of the IGM. We also introduce the threshold probability functions, a one-dimensional two-point statistic adapted from material sciences that can be applied to SDSS data to detect 50 Mpc IGM thermal inhomogeneities arising from He II reionization. Chapter 2 discusses the effect of continuum biases in the TDR measured from high-resolution Lyalpha forest spectra in the context of recent evidence for an inverted (gamma < 1) TDR. We argue that forward modeling of continuum errors in mock spectra are necessary to make robust estimates of the TDR. Motivated by the importance of accurate continuum estimation in Lya forest analysis, Chapter 3 introduces the mean-flux regulated/principal component analysis (MF-PCA) continuum estimation technique. We show using mock spectra that this technique can achieve continuum accuracies of < 10% and < 4% in noisy spectra of S/N 2 and S/N 5, respectively. We have also publicly released 13,000 continua from SDSS Data Release 7. In Chapter 4, we measure the flux PDF from BOSS, drawing from an overall sample of 30,000 Lya forest sightlines. This uses a novel procedure for optimally combining the multiple BOSS exposures and estimating the spectral noise contribution. Comparing a high signal-to-noise subsample in BOSS with mock spectra generated from detailed hydrodynamical simulations, we find that the flux PDF from BOSS at 2 < z < 3 is consistent with an isothermal TDR, consistent with theoretical expectations from He II reionization.

  3. Low Levels of IgM Antibodies against an Advanced Glycation Endproduct-Modified Apolipoprotein B100 Peptide Predict Cardiovascular Events in Nondiabetic Subjects.

    PubMed

    Engelbertsen, Daniel; Vallejo, Jenifer; Quch, Tm Dan; Fredrikson, Gunilla Nordin; Alm, Ragnar; Hedblad, Bo; Bjrkbacka, Harry; Rothstein, Thomas L; Nilsson, Jan; Bengtsson, Eva

    2015-10-01

    Increased glucose levels are associated with the generation of advanced glycation endproduct (AGE) modifications. Interaction between AGE-modified plaque components and immune cells is believed to have an important role in the development of vascular complications in diabetes. Methylglyoxal (MGO) is one type of reactive aldehyde that gives rise to AGE modification. The present study analyzed whether autoantibodies against MGO-modified epitopes of the low-density lipoprotein apolipoprotein B (apoB) 100 predict cardiovascular events. A library consisting of 302 peptides comprising the complete apoB100 molecule was screened to identify peptides targeted by MGO-specific autoantibodies. Peptide (p) 220 (apoB amino acids 3286-3305) was identified as a major target. Baseline IgM and IgG against MGO-peptide 220 (p220) were measured in 700 individuals from the Malm Diet and Cancer Cohort. A total of 139 cardiovascular events were registered during the 15-y follow-up period. Controlling for major cardiovascular risk factors demonstrated that subjects in the lowest tertile of MGO-p220 IgM had an increased risk for cardiovascular events (hazard ratio [95% confidence interval]: 2.07 [1.22-3.50]; p(trend) = 0.004). Interestingly, the association between MGO-p220 IgM and cardiovascular events remained and even tended to become stronger when subjects with prevalent diabetes were excluded from the analysis (2.51 [1.37-4.61]; p(trend) = 0.002). MGO-p220 IgM was inversely associated with blood glucose, but not with oxidized low-density lipoprotein. Finally, we demonstrate that anti-MGO-p220 IgM is produced by B1 cells. These data show that subjects with low levels of IgM recognizing MGO-modified p220 in apoB have an increased risk to develop cardiovascular events and that this association is present in nondiabetic subjects. PMID:26290603

  4. Characterization of RAG1 and IgM (mu chain) marking development of the immune system in red-spotted grouper (Epinephelus akaara).

    PubMed

    Mao, Ming-Guang; Lei, Ji-Lin; Alex, Perlvarez-Marn; Hong, Wan-Shu; Wang, Ke-Jian

    2012-10-01

    In vertebrates, lymphoid-specific recombinase protein encoded by recombination-activating genes (RAG1/2) plays a key role in V(D)J recombination of the T-cell receptor and B-cell receptor. In this study, both RAG1 and the immunoglobulin M (IgM) mu chain were cloned to characterize their potential role in the immune defense at developmental stages of red-spotted grouper, Epinephelus akaara. The open reading frame (ORF) of E.akaara RAG1 included 2778 nucleotide residues encoding a putative protein of 925 amino acids, while the ORF of the IgM mu chain had 1734 nucleotide residues encoding 578 amino acids including variable (VH) and constant (CH1-CH2-CH3-CH4) regions. E.akaara RAG1 was composed of a zinc-binding dimerization domain (ZDD) with a RING finger and zinc finger A (ZFA) in the non-core region and a nonamer-binding region (NBR), with a zinc finger B (ZFB), the central and C-terminal domains in the core region. Tridimensional models of the ZDD and NBR of E.akaara RAG1 were constructed for the first time in fishes, while a 3D model of the E.akaara IgM mu chain was also clarified. The RAG1 mRNA was only detected in the thymus and kidney of 4-month and 1.5-year old groupers using qPCR, and the RAG1 protein was confirmed using western blotting and immunohistochemistry. The IgM mu mRNA was examined in most tissues except the gonad. RAG1 and IgM mu gene expression were observed at 15dph (days post-hatching) and 23dph respectively, and increased to a higher level at 37dph. In addition, this was the first time that the morphology of the E.akaara thymus was characterized. The oval-shaped thymus of 4-month old fish was clearly seen and there were amounts of T lymphocytes present. The results suggested that the immune action of E.akaara was likely to start to develop around 15dph to 29dph. The transcript level of the RAG1 gene and the number of lymphocytes in the thymus between 4-month and 1.5-year old groupers indicated that age-related thymic atrophy also occurs in fishes. The similar functional structures of RAG1 and IgM protein between fish and mammals indicated that teleost species share a similar mechanism of V(D)J recombination with higher vertebrates. PMID:22796426

  5. Validation of an In-House Assay for Cytomegalovirus Immunoglobulin G (CMV IgG) Avidity and Relationship of Avidity to CMV IgM Levels

    PubMed Central

    Prince, Harry E.; Leber, Amy L.

    2002-01-01

    Measurement of cytomegalovirus (CMV)-specific immunoglobulin G (IgG) avidity has proven to be a powerful tool for distinguishing primary from nonprimary CMV infection. An in-house enzyme-linked immunosorbent assay (ELISA) for measuring CMV IgG avidity was validated using 84 sera from pregnant women who had recently seroconverted following primary CMV infection and 74 sera from individuals with past CMV infection (IgG-positive and IgM-negative profile). Of the 84 sera from pregnant women, 73 sera were collected within 120 days of the last IgG-negative sample, and 72 of these 73 sera (99%) exhibited an avidity index (AI) of <50%. In contrast, 71 of 74 (96%) sera from individuals with past CMV infection exhibited CMV AI values of >60%. Thus, low avidity in the in-house ELISA was defined as an AI of ?50%, whereas high avidity was defined as an AI of ?60%. In additional studies, the relationship between CMV IgG avidity and CMV IgM levels was examined using 64 CMV IgG-positive sera (time since seroconversion unknown) exhibiting equivocal or positive results in a CMV IgM capture ELISA (Diamedix). Of these 64 sera, 29 exhibited IgM index values of ?3.0, and 27 of these 29 (93%) exhibited low IgG avidity. A similar trend was observed when a subset of these 64 sera (n = 48) was tested in another CMV IgM capture ELISA (Trinity); of 18 sera with IgM index values of ?3.0, 17 (94%) exhibited low IgG avidity. These findings demonstrate the validity of an in-house ELISA for CMV IgG avidity and further show that strong reactivity of CMV IgG-positive sera in either of two CMV IgM capture assays is a reliable indicator of low CMV IgG avidity, and thus, recent CMV infection. PMID:12093680

  6. Characterization of additional rabbit IgM allotypes and the effect of suppression of a VH locus allotypes on the expression of n C. mu. locus allotype

    SciTech Connect

    Gilman-Sachs, A.; Roux, K.H.; Horing, W.J.; Dray, S.

    1982-01-01

    Anti-allotype antisera were produced that identified eight rabbit IgM allotypic specificities, n80, n81, n82, n83, n84, n85, n86, and n87. The n locus C..mu.. genes controlling these IgM allotypic specificities are closely linked to the a (VH subgroup) locus. The genes controlling these allotypic specificities were found to be in the heavy chain chromosomal region and were assigned to 11 haplotypes present in our rabbit colony. The n locus and a locus genes appeared in the haplotypes in six combinations: a/sup 1/n/sup 81/, a/sup 2/n/sup 81,n87/, a/sup 1/n/sup 80,83/, a/sup 2/n/sup 80,82,87/, a/sup 3/n/sup 81,84,85/ and a/sup 3/n/sup 80,84,86,87/. By radioprecipitation analysis, 70 to 80% of serum IgM reacts with the antiserum directed to each n locus allotypic specificity found encoded in one haplotype; thus, each allotypic specificity of the haplotype is present on the same IgM molecule. When sera from a locus allotype-suppressed homozygous rabbits were tested for expression of each n locus allotypic specificity, n80, n81, and n87 were still expressed, whereas n82, n83, n84, n85, and n86 were not. These data provide direct evidence that some IgM specificities are expressed independently of the a locus (i.e., ''true''), and other s are dependent on the expression of an a locus specificity (i.e., conformational). The expression of the ''true'' allotypic specificities probably reflects genetic control of the germline C..mu.. gene, and the expression of ''conformationally dependent'' allotypic specificities probably reflects the interaction of VH and C..mu.. gene segments. This distinction is important and must be recognized when evaluating the genetics and structure of the IgM molecule.

  7. Syndrome of selective IgM deficiency with severe T cell deficiency associated with disseminated cutaneous mycobacterium avium intracellulaire infection

    PubMed Central

    Gharib, Asal; Louis, Ankmalika Gupta; Agrawal, Sudhanshu; Gupta, Sudhir

    2015-01-01

    Cutaneous non-disseminated, non-tuberculous mycobacterial infections have been reported in both immunocompetent and immunocompromised subjects. Systemic Mycobacterium avium intracellulaire (MAI) have been reported in non-HIV patients with Idiopathic CD4 lymphocytopenia. We report a comprehensive immunological analysis in syndrome of selective IgM deficiency and T lymphocytopenia (both CD4+ and CD8+) with disseminated cutaneous MAI infection. Nave (TN) and Central memory (TCM) subsets of both CD4+ and CD8+ T cells were decreased, whereas terminally differentiated effector memory (TEMRA) subset of CD4+ and CD8+ T cells were markedly increased. IFN-? producing T cells were markedly decreased. Although CD14highCD16- proinflammatory monocytes were modestly increased, IFN-?R+ monocytes were markedly decreased. The expression of TLR3, TLR5, TLR7, and TLR9 on monocytes was decreased. Germinal center B cells (CD19+IgD-CD38+CD27lo) and B1 cells (CD20+CD27+CD43+CD70-) were markedly decreased. A role of immune alterations, including B cells and antibodies in disseminated cutaneous MAI infection is discussed. PMID:26550546

  8. Functionally Responsive Self-Reactive B Cells of Low-Affinity Express Reduced Levels of Surface IgM1

    PubMed Central

    Kirchenbaum, Greg A.; St. Clair, James B.; Detanico, Thiago; Aviszus, Katja; Wysocki, Lawrence J.

    2014-01-01

    SUMMARY Somatic gene rearrangement generates a diverse repertoire of B cells, including B cell receptors (BCR) possessing a range of affinities for self-Ag. Newly generated B cells express high and relatively uniform amounts of surface IgM (sIgM), while follicular (FO) B cells express sIgM at widely varying levels. It is plausible, therefore, that down-modulation of sIgM serves as a mechanism to maintain weakly self-reactive B cells in a responsive state by decreasing their avidity for self-Ag. We tested this hypothesis by performing comparative functional tests with FO IgMhi and IgMlo B cells from the unrestricted repertoire of wildtype (WT) mice. We found that FO IgMlo B cells mobilized Ca2+ equivalently to IgMhi B cells when the same number of sIgM molecules was engaged. In agreement, FO IgMlo B cells were functionally competent to produce an antibody response following adoptive transfer. The FO IgMlo cell population had elevated levels of Nur77 transcript, and was enriched with nuclear-reactive specificities. Hybridoma sampling revealed that these BCR were of low affinity. Collectively, these results suggest that sIgM down-modulation by low-affinity, self-reactive B cells preserves their immunocompetence and circumvents classical peripheral tolerance mechanisms that would otherwise reduce diversity within the B cell compartment. PMID:24375379

  9. In vitro synthesis of IgM rheumatoid factor in response to Staphylococcus aureus, by lymphocytes from healthy adults

    SciTech Connect

    Goldstein, R.; Karsh, J.

    1986-12-01

    Peripheral blood mononuclear cells from 20 healthy adults were tested in vitro for the production of IgM rheumatoid factor (RF) in response to Staphylococcus aureus Cowan I (SAC) or pokeweed mitogen. Fifteen of the 20 normal subjects produced greater than or equal to 4 ng/ml IgM-RF (mean +/- SD 46 +/- 55 ng/ml) in response to SAC, compared with only 2 of 20 who produced greater than or equal to 4 ng/ml IgM-RF (mean +/- SD 2 +/- 4 ng/ml) in response to pokeweed mitogen (P = 0.0001). Separation and reconstitution of autologous T and B cell-enriched fractions, with and without prior T cell irradiation, provided evidence for a radiosensitive T helper/inducer cell involved in the IgM-RF response to SAC in 70% of the normal subjects studied. SAC appears to be a potent stimulus of IgM-RF production, with a cellular mechanism distinct from that of other in vitro systems.

  10. Syndrome of selective IgM deficiency with severe T cell deficiency associated with disseminated cutaneous mycobacterium avium intracellulaire infection.

    PubMed

    Gharib, Asal; Louis, Ankmalika Gupta; Agrawal, Sudhanshu; Gupta, Sudhir

    2015-01-01

    Cutaneous non-disseminated, non-tuberculous mycobacterial infections have been reported in both immunocompetent and immunocompromised subjects. Systemic Mycobacterium avium intracellulaire (MAI) have been reported in non-HIV patients with Idiopathic CD4 lymphocytopenia. We report a comprehensive immunological analysis in syndrome of selective IgM deficiency and T lymphocytopenia (both CD4+ and CD8+) with disseminated cutaneous MAI infection. Nave (TN) and Central memory (TCM) subsets of both CD4+ and CD8+ T cells were decreased, whereas terminally differentiated effector memory (TEMRA) subset of CD4+ and CD8+ T cells were markedly increased. IFN-? producing T cells were markedly decreased. Although CD14(high)CD16- proinflammatory monocytes were modestly increased, IFN-?R+ monocytes were markedly decreased. The expression of TLR3, TLR5, TLR7, and TLR9 on monocytes was decreased. Germinal center B cells (CD19+IgD-CD38+CD27(lo)) and B1 cells (CD20+CD27+CD43+CD70-) were markedly decreased. A role of immune alterations, including B cells and antibodies in disseminated cutaneous MAI infection is discussed. PMID:26550546

  11. A novel immunosensor for detecting toxoplasma gondii-specific IgM based on goldmag nanoparticles and graphene sheets.

    PubMed

    Jiang, Shuting; Hua, Erhui; Liang, Mo; Liu, Bei; Xie, Guoming

    2013-01-01

    A novel electrochemical immunosensor for detecting toxoplasma gondii-specific IgM (Tg-IgM) was constructed based on goldmag (Au-Fe(3)O(4)) nanoparticles and graphene sheets (GS). Thionine (Thi), as a mediator, was first electropolymerized on a nafion-GS (Nf-GS) modified electrode. Subsequently, gold nanoparticles (AuNPs) were attached onto the poly-thionine film through ?-stacking interactions, and then were used to immobilize toxoplasma gondii antigen (Tg-Ag) for immunosensor fabrication. A sandwich-type immunoassay for Tg-IgM was performed using Au-Fe(3)O(4) labeled anti-IgM-horseradish peroxidase (HRP) as trace label. Electrochemical detection was carried out in the presence of H(2)O(2) as HRP substrate. Using Au-Fe(3)O(4) provided a simple, non-chemical damaging method for regeneration, and enhanced the HRP reduction ability toward H(2)O(2). The AuNPs/Thi/Nf-GS nanocomposite also had good conductivity and biocompatibility, which effectively improved the immunosensor sensitivity. Under optimal conditions, the immunosensor can detect Tg-IgM in two linear ranges from 0.0375 to 1.2 AU mL(-1) and from 2.0 to 18 AU mL(-1) with a detection limit of 0.016 AU mL(-1) (S/N=3). The immunosensor exhibited good reproducibility, stability, and selectivity as well. PMID:23010058

  12. Selective gene therapy for prostate cancer cells using liposomes conjugated with IgM type monoclonal antibody against prostate-specific membrane antigen.

    PubMed

    Ikegami, Shusei; Tadakuma, Takushi; Yamakami, Kazuo; Ono, Takeshi; Suzuki, Satoshi; Yoshimura, Ichiro; Asano, Tomohiko; Hayakawa, Masamichi

    2005-03-01

    Prostate cancer cells express prostate-specific membrane antigen (PSMA). We developed an IgM type monoclonal antibody against PSMA. The antibody was coupled to poly-L-lysine and thereafter this conjugate was mixed with cationic liposomes containing plasmid DNA. The antibody-liposome complex was tested whether it could deliver the gene of interest selectively to the PSMA positive cells. As assessed by beta-galactosidase reporter gene, the transfection efficiency was 13.2% with anti-PSMA-liposome complex as compared to 4% with control IgM liposome complex. In contrast, no such differences were observed in PSMA negative PC-3, DU145 and T24 cells. Furthermore, in the suicide gene therapy in vitro with thymidine kinase gene plus ganciclovir system, anti-PSMA liposome complex demonstrated a selective growth inhibitory effect on PSMA positive LNCaP cells but not on PSMA negative cell lines. PMID:16130896

  13. Comparison of ELISA and immunoassays for measurement of IgG and IgM antibody to West Nile virus in human sera against virus neutralisation.

    PubMed

    Niedrig, M; Sonnenberg, K; Steinhagen, K; Paweska, J T

    2007-01-01

    Two commercial assays for the detection of IgG antibody to West Nile virus (WNV), an indirect enzyme-linked immunosorbent assay (I-ELISA) and indirect fluorescent antibody test (IFAT), were evaluated against the virus neutralisation test. Excellent agreement with the virus neutralisation was obtained with both tests, i.e., 99.5% by I-ELISA and 100% by IFAT. The well-known serological cross-reactivity within the family of the Flaviviridae was analysed using sera with known antibodies against dengue virus, tick borne encephalitis virus and yellow fever virus. IgM and/or IgG positive sera were examined for reactivity by WNV-ELISA and WNV-IFAT. While cross-reactivity between 0 and 18.2% was recorded with IgM positive sera, there was extensive cross-reactivity of 15.7-100% with IgG positive sera. PMID:17084464

  14. Development and preliminary evaluation of an IgM dot-immunobinding assay (IgM-DIA) for rapid serodiagnosis of scrub typhus infection.

    PubMed

    Koay, A S; Tay, S T; Cheong, Y M; Yasin, R M

    1995-06-01

    An IgM dot-immunobinding assay (IgM-DIA) was developed for the diagnosis of scrub typhus infection. The whole cell antigens of Karp, Kato and Gilliam strains of Rickettsia tsutsugamushi were immobilized onto nitrocellulose paper and reacted with patients sera. The presence of IgM R. tsutsugamushi specific antibody in the patient sera could be detected by the observation of a visible brown dot on the nitrocellulose paper. The IgM-DIA has a sensitivity of 90.4% and specificity of 81.4% as compared to the indirect immunoperoxidase test. The IgM-DIA is rapid, simple, cost-effective, does not require microscope or incubator. It is recommended as a rapid screening test for the diagnosis of scrub typhus infection in the field or rural area within the hyperendemic region. PMID:8629074

  15. The effect of the plant lectins phytohaemagglutinin and concanavalin A on human T cell populations bearing receptors for IgG and IgM.

    PubMed Central

    Gomez-Reino, J; Habicht, G S

    1980-01-01

    The effect of long-term culture with the plant lectins phytohaemagglutinin (PHA) and concanavalin A (con A) on the percentages of human T cells bearing Fc receptors for IgG (TG) and IgM (TM) was investigated. Con A produced an early increase in the percentage of TG cells as compared to control cells cultured without mitogen. TM cells decreased. PHA suppressed the percentages of both TG and TM. These changes were not due to loss of cell viability nor to loss of cell surface receptors in general since up to 98% of the cells continued to form sheep erythrocyte rosettes in the virtual absence of IgM Fc receptors. PMID:6969156

  16. A point-of-care test for measles diagnosis: detection of measles-specific IgM antibodies and viral nucleic acid

    PubMed Central

    Slibinskas, Rimantas; Chua, Kaw Bing; Nigatu, Wondatir; Brown, Kevin E; Sasnauskas, Kestutis; Samuel, Dhanraj; Brown, David

    2011-01-01

    Abstract Objective To evaluate the performance of a newly developed point-of-care test (POCT) for the detection of measles-specific IgM antibodies in serum and oral fluid specimens and to assess if measles virus nucleic acid could be recovered from used POCT strips. Methods The POCT was used to test 170 serum specimens collected through measles surveillance or vaccination programmes in Ethiopia, Malaysia and the Russian Federation: 69 were positive for measles immunoglobulin M (IgM) antibodies, 74 were positive for rubella IgM antibodies and 7 were positive for both. Also tested were 282 oral fluid specimens from the measles, mumps and rubella (MMR) surveillance programme of the United Kingdom of Great Britain and Northern Ireland. The Microimmune measles IgM capture enzyme immunoassay was the gold standard for comparison. A panel of 24 oral fluids was used to investigate if measles virus haemagglutinin (H) and nucleocapsid (N) genes could be amplified by polymerase chain reaction directly from used POCT strips. Findings With serum POCT showed a sensitivity and specificity of 90.8% (69/76) and 93.6% (88/94), respectively; with oral fluids, sensitivity and specificity were 90.0% (63/70) and 96.2% (200/208), respectively. Both H and N genes were reliably detected in POCT strips and the N genes could be sequenced for genotyping. Measles virus genes could be recovered from POCT strips after storage for 5 weeks at 20–25 °C. Conclusion The POCT has the sensitivity and specificity required of a field-based test for measles diagnosis. However, its role in global measles control programmes requires further evaluation. PMID:21897488

  17. Seroprevalence of rubella-specific IgM and IgG antibodies among pregnant women seen in a tertiary hospital in Nigeria

    PubMed Central

    Olajide, Okikiola M; Aminu, Maryam; Randawa, Abdullahi J; Adejo, Daniel S

    2015-01-01

    Background Rubella is a contagious viral infection that in pregnant women leads to the infection of a developing fetus, causing fetal death or congenital rubella syndrome. Objective Pregnant women are not routinely screened for rubella in Nigeria. Epidemiological data on rubella is therefore necessary to create awareness and sensitize health care administrators and providers. Materials and methods A cross-sectional study was carried out at Ahmadu Bello University Teaching Hospital between June and August 2012 to determine the prevalence of immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies to rubella virus in pregnant women using enzyme-linked immunosorbent assay kits. Seroprevalence was compared among 160 pregnant women attending the antenatal clinic of Ahmadu Bello University Teaching Hospital and 20 nonpregnant women of childbearing age studying at Ahmadu Bello University. Prior to sample collection, questionnaires were administered to the women to obtain data on sociodemographics, awareness and knowledge of rubella, possible risk factors, and clinical symptoms associated with the viral infection. Results Of the 160 pregnant women, 149 (93.1%) and 62 (38.8%) were positive for anti-rubella IgM and IgG antibodies, respectively. Similarly, of the 20 nonpregnant women, 18 (90%) and eight (40%) were positive for rubella IgG and IgM antibodies, respectively. None of the possible risk factors studied were significantly associated with infection. Age and other sociodemographic factors were of little significance, and awareness of rubella was low. Conclusion The prevalence of rubella was high in both pregnant (93.1%) and nonpregnant women (90%), suggesting sustained transmission, which further suggests endemicity. The presence of rubella IgM and IgG antibodies in pregnant women predisposes babies to congenital rubella syndrome and emphasizes the need for the initiation of a national rubella vaccination program in Nigeria. PMID:25610003

  18. Outcome of Patients With IgD and IgM Multiple Myeloma Undergoing Autologous Hematopoietic Stem Cell Transplantation: A Retrospective CIBMTR Study

    PubMed Central

    Reece, Donna E.; Vesole, David H.; Shrestha, Smriti; Zhang, Mei-Jie; Prez, Waleska S.; Dispenzieri, Angela; Milone, Gustavo A.; Abidi, Muneer; Atkins, Harold; Bashey, Asad; Bredeson, Christopher N.; Boza, Willem Bujan; Freytes, Csar O.; Gale, Robert Peter; Gajewski, James L.; Gibson, John; Hale, Gregory A.; Kumar, Shaji; Kyle, Robert A.; Lazarus, Hillard M.; McCarthy, Philip L.; Pavlovsky, Santiago; Roy, Vivek; Weisdorf, Daniel J.; Wiernik, Peter H.; Hari, Parameswaran N.

    2012-01-01

    Introduction Immunoglobulin D (IgD) and IgM multiple myeloma represent uncommon immunoglobulin isotypes, accounting for 2% and 0.5% of cases, respectively. Limited information is available regarding the prognosis of these isotypes, but they have been considered to have a more aggressive course than the more common immunoglobulin G (IgG) and IgA isotypes. In particular, the outcome after autologous hematopoietic stem cell transplantation (auto-HCT) has not been well defined. Patients and Methods Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we identified 36 patients with IgD and 11 patients with IgM myeloma among 3578 myeloma patients who received intensive therapy and auto-HCT over a 10-year period. Results The progression-free and overall survival probabilities at 3 years were 38% (95% CI, 21%-56%) and 69% (95% CI, 51%-84%) for IgD myeloma, and 47% (95% CI, 17%-78%) and 68% (95% CI, 36%-93%), respectively, for IgM disease. Although formal statistical analysis was limited by the small sample size, these results were comparable to those for IgG and IgA patients autografted during the same time period. Transplantation-related mortality and disease relapse/progression of myeloma were also similar for all isotypes. Conclusion This analysis demonstrates comparable outcomes in all immunoglobulin isotypes. Therefore, auto-HCT should be offered to eligible patients with IgD and IgM myeloma. PMID:21156462

  19. I. Studies on pyridine dinucleotide transhydrogenase in rat liver mitochondria. II. Identification of the tissue and cellular sites of catabolism of IgM in the rat

    SciTech Connect

    Weis, J.K.

    1988-01-01

    The orientation of the transmembrane enzyme, pyridine dinucleotide transhydrogenase, in the inner mitochondrial membrane of rat liver has been determined by evaluating effects of proteases on the integrity of the enzyme in mitoplasts and submitochondrial particles. Following treatment of these membranes with the non-specific protease, proteinase K, antigenic proteolytic products were detected by immunoblot analysis using polyclonal antibody prepared against purified bovine heart enzyme. Information from these proteolysis studies was used to construct a model of the orientation of transhydrogenase in the inner mitochondrial membrane. In this work, I have used the residualizing label, dilactitol-{sup 125}I-tyramine ({asterisk}I-DLT) to identify the tissue and cellular sites of catabolism of the immunoglobulin, IgM. Purified IgM was labeled conventionally with {sup 125}I or with the residualizing label, {asterisk}I-DLT. The circulating half-life of the protein, 2.7 {plus minus} 0.3 days, was the same when measured using either label, indicating that the residualizing label does not affect the kinetics of the protein's catabolism in vivo. At 2.4 or 5.1 days post injection, the liver contained the major fraction of catabolized protein compared to all the other organs in the body. Additionally, following collagenase digestion of the liver, the hepatocytes were shown to be 77% responsible for the catabolism of IgM by the liver. Autoradiography of the liver revealed that the remaining 23% of IgM catabolized by the liver was due to the Kupffer cells.

  20. Production of Anti-LPS IgM by B1a B Cells Depends on IL-1? and Is Protective against Lung Infection with Francisella tularensis LVS

    PubMed Central

    Lantier, Louis; Reynolds, Joseph M.; Ceballos-Olvera, Ivonne; Re, Fabio

    2015-01-01

    The role of IL-1? and IL-18 during lung infection with the gram-negative bacterium Francisella tularensis LVS has not been characterized in detail. Here, using a mouse model of pneumonic tularemia, we show that both cytokines are protective, but through different mechanisms. Il-18-/- mice quickly succumb to the infection and showed higher bacterial burden in organs and lower level of IFN? in BALF and serum compared to wild type C57BL/6J mice. Administration of IFN? rescued the survival of Il-18-/- mice, suggesting that their decreased resistance to tularemia is due to inability to produce IFN?. In contrast, mice lacking IL-1 receptor or IL-1?, but not IL-1?, appeared to control the infection in its early stages, but eventually succumbed. IFN? administration had no effect on Il-1r1-/- mice survival. Rather, Il-1r1-/- mice were found to have significantly reduced titer of Ft LPS-specific IgM. The anti-Ft LPS IgM was generated in a IL-1?-, TLR2-, and ASC-dependent fashion, promoted bacteria agglutination and phagocytosis, and was protective in passive immunization experiments. B1a B cells produced the anti-Ft LPS IgM and these cells were significantly decreased in the spleen and peritoneal cavity of infected Il-1b-/- mice, compared to C57BL/6J mice. Collectively, our results show that IL-1? and IL-18 activate non-redundant protective responses against tularemia and identify an essential role for IL-1? in the rapid generation of pathogen-specific IgM by B1a B cells. PMID:25768794

  1. Characterization and removal of aggregates formed by nonspecific interaction of IgM monoclonal antibodies with chromatin catabolites during cell culture production.

    PubMed

    Gan, Hui Theng; Lee, Jeremy; Latiff, Sarah Maria Abdul; Chuah, Cindy; Toh, Phyllicia; Lee, Wan Yee; Gagnon, Pete

    2013-05-24

    We observed that IgM monoclonal antibodies and aggregates in mammalian cell culture supernatants were associated nonspecifically with nucleosomes, DNA, and histone proteins derived from nuclei of host cells that died during antibody production. A series of multimodal sample treatments were evaluated for their ability to selectively remove these contaminants without significant antibody loss. The first consisted of adding 2,5-dioxo-4-imidazolidinyl urea (allantoin) and the DNA intercalating agent 7-ethoxyacridine-3,9-diamine (ethacridine), then flowing the supernatant through a column of mixed porous particles bearing metal affinity, anion exchange, and cation exchange functionalities. A one-step variant of the method was to mix chromatography particles with the allantoin-ethacridine-treated supernatant. An alternative one-step treatment consisted of passing untreated cell supernatant through a chelating monolith in tandem with an anion exchange monolith. All methods eliminated high molecular weight aggregates, and reduced smaller aggregates to 2-4%. They also achieved 98% DNA reduction, 99% reduction of nucleosomes and histones, 30-70% reduction of general host proteins, and 98% IgM recovery. Size exclusion chromatography analysis indicated that IgG monoclonal antibodies benefit similarly from treatment. Subsequent IgM purification reduced DNA levels beneath the level of detectability by fluorescent dye intercalation, histones to less than 10 parts per million by ELISA, and aggregates to less than 0.05% by size exclusion chromatography. The results point to chromatin catabolites as promoters of antibody aggregate formation. PMID:23598159

  2. The combination of specific IgM antibodies and IgG antibodies of low avidity does not always indicate primary infection with cytomegalovirus.

    PubMed

    Lumley, S; Patel, M; Griffiths, P D

    2014-05-01

    The detection of CMV specific IgM antibodies coupled with IgG antibodies of low avidity is taken as diagnostic of primary CMV infection. In a study of 64 pregnant women referred for avidity testing, six women were identified with bloods with positive IgM and low/equivocal avidity IgG on the Abbott Architect assay persisting over 18 weeks. Avidity increased to an "equivocal" level in two women over the course of follow up but remained "low" in four women. On repeat testing with the Diasorin Liaison assay, bloods from two women with low avidity with Architect gave high avidity results with Liaison. Blood from one woman giving low/equivocal results with Architect was reported as moderate avidity on repeat with Liaison. There is concern from these small numbers of cases that some women with positive IgM and low avidity IgG using the Abbott Architect assay may not have primary infections. This implies that they could be entered inappropriately into trials of experimental treatments aiming to prevent transmission of CMV to the fetus if the laboratory is asked to test patients for this purpose. It is suggested that larger series of patients should be examined to determine how frequently this phenomenon occurs. PMID:24395084

  3. Gold magnetic nanoparticle conjugate-based lateral flow assay for the detection of IgM class antibodies related to TORCH infections.

    PubMed

    Li, Xingxing; Zhang, Qinlu; Hou, Peng; Chen, Mingwei; Hui, Wenli; Vermorken, Alphons; Luo, Zhiyi; Li, Hong; Li, Qin; Cui, Yali

    2015-11-01

    In this study, a lateral flow immunochromatographic assay (LFIA) system for the detection of immunoglobulin M (IgM) antibodies, related to TORCH [(T)oxoplasmosis, (O)ther agents, (R)ubella (also known as German Measles), (C)ytomegalovirus, and (H)erpes simplex virus infections], based on gold magnetic nanoparticles, was established. Following modification with poly(methacrylic acid), the gold magnetic nanoparticles conjugated with an anti‑human IgM antibody (μ‑chain specific) to construct a probe. A lateral flow assay device was constructed based on these conjugates. IgM antibodies to four types of pathogens, notably toxoplasmosis, rubella virus, cytomegalovirus and herpes simplex virus type 2, were detected using this device. Compared with commercial colloidal gold‑based LFIA strips, our method exhibited higher sensitivity. No interference with triglycerides, hemoglobin and bilirubin occurred, and no cross‑reactivity was noted among the four pathogens. The gold magnetic nanoparticle‑LFIA strips were used to assess 41 seropositive and 121 seronegative serum samples. The sensitivity was 100% (162/162) and the specificity was 100% (162/162). This method cannot only be used for the detection of TORCH IgM-specific antibodies, but it can potentially be developed for use in the diagnosis of other acute or recently identified autoimmune diseases. PMID:26329478

  4. Detection of IgM Antibrucella Antibody in the Absence of IgGs: A Challenge for the Clinical Interpretation of Brucella Serology

    PubMed Central

    Sols Garca del Pozo, Julin; Lorente Ortuo, Santiago; Navarro, Elena; Solera, Javier

    2014-01-01

    The use of enzyme-linked immunosorbent assay (ELISA) for the detection of IgG and IgM antibodies antibrucella has become widespread in the diagnosis of human brucellosis. IgM anti-Brucella antibodies are indicative of acute infection. Between 20092013, 5307 patients were evaluated for serologic diagnosis at the Microbiology Laboratory of the Albacete General Hospital. A ELISA IgM-positive, IgG-negative anti-Brucella antibody serology pattern was detected in 17 of those patients. Epidemiology data, symptoms, laboratory data, treatment and outcome from these patients were reviewed. Sixteen patients presented with musculoskeletal pain, fatigue and/or fever and 1 was asymptomatic. Five patients received treatment with doxycycline combined with rifampin, gentamycin or streptomycin during 612 weeks, with no improvement. None of the 17 patients were finally diagnosed with brucellosis. Our results indicate that anti-Brucella IgM positive serology, per se, is not enough to diagnose acute brucellosis and other methods should be used for confirmation. Brucella serology data should be interpreted taking into account the patient's clinical history and epidemiological context. PMID:25474572

  5. Evaluation of semi-quantitative PCR and IgG & IgM ELISA in diagnosis of toxoplasmosis in females with miscarriage.

    PubMed

    Abdel-Hameed, Dina M; Hassanein, Omayma

    2004-08-01

    One hundred female (age 20-42 yrs) patients were classified into group I: 40 patients presented with abortion in the first trimester; group II: 33 patients with abortion in the second trimester and group III: 27 patients with intrauterine fetal death (IUFD). The positive percentages of semi-quantitative PCR and both IgG & IgM ELISA were 38% and 35% respectively. Ten (26.3%) cases out of 38 were positive for toxoplasmosis by both PCR and ELISA-IgG, while 5 (13.2%) cases out of 38 were positive by both PCR and ELISA-IgM, whereas 16 (42.1%) cases out of 38 PCR positive cases were positive by both ELISA IgG & IgM. Sensitivity and specificity of both ELISA IgG and IgM were 81.57% & 93.54% respectively. False negative by ELISA were found in 7 cases out of 38 positive toxoplasmosis cases detected by semi-quantitative PCR. Three cases out of the 7 cases with false negative by ELISA were detected with a trophozoite copy load of 10(1) trophozoite /mL in the blood sample by semi-quantitative PCR. So, the semi-quantitative PCR detected low levels of parasite DNA recommending its usefulness especially in the early stages of the disease when low amount of antibodies can't be detected by serological method or even by the conventional PCR. PMID:15287178

  6. Heterozygous Mutation in IκBNS Leads to Reduced Levels of Natural IgM Antibodies and Impaired Responses to T-Independent Type 2 Antigens

    PubMed Central

    Pedersen, Gabriel K.; Ádori, Monika; Stark, Julian M.; Khoenkhoen, Sharesta; Arnold, Carrie; Beutler, Bruce; Karlsson Hedestam, Gunilla B.

    2016-01-01

    Mice deficient in central components of classical NF-κB signaling have low levels of circulating natural IgM antibodies and fail to respond to immunization with T-independent type 2 (TI-2) antigens. A plausible explanation for these defects is the severely reduced numbers of B-1 and marginal zone B (MZB) cells in such mice. By using an ethyl-N-nitrosourea mutagenesis screen, we identified a role for the atypical IκB protein IκBNS in humoral immunity. IκBNS-deficient mice lack B-1 cells and have severely reduced numbers of MZB cells, and thus resemble several other strains with defects in classical NF-κB signaling. We analyzed mice heterozygous for the identified IκBNS mutation and demonstrate that these mice have an intermediary phenotype in terms of levels of circulating IgM antibodies and responses to TI-2 antigens. However, in contrast to mice that are homozygous for the IκBNS mutation, the heterozygous mice had normal frequencies of B-1 and MZB cells. These results suggest that there is a requirement for IκBNS expression from two functional alleles for maintaining normal levels of circulating natural IgM antibodies and responses to TI-2 antigens. PMID:26973645

  7. Functional capacities of human IgM memory B cells in early inflammatory responses and secondary germinal center reactions

    PubMed Central

    Seifert, Marc; Przekopowitz, Martina; Taudien, Sarah; Lollies, Anna; Ronge, Viola; Drees, Britta; Lindemann, Monika; Hillen, Uwe; Engler, Harald; Singer, Bernhard B.; Kppers, Ralf

    2015-01-01

    The generation and functions of human peripheral blood (PB) IgM+IgD+CD27+ B lymphocytes with somatically mutated IgV genes are controversially discussed. We determined their differential gene expression to naive B cells and to IgM-only and IgG+ memory B cells. This analysis revealed a high similarity of IgM+(IgD+)CD27+ and IgG+ memory B cells but also pointed at distinct functional capacities of both subsets. In vitro analyses revealed a tendency of activated IgM+IgD+CD27+ B cells to migrate to B-cell follicles and undergo germinal center (GC) B-cell differentiation, whereas activated IgG+ memory B cells preferentially showed a plasma cell (PC) fate. This observation was supported by reverse regulation of B-cell lymphoma 6 and PR domain containing 1 and differential BTB and CNC homology 1, basic leucine zipper transcription factor 2 expression. Moreover, IgM+IgD+CD27+ B lymphocytes preferentially responded to neutrophil-derived cytokines. Costimulation with catecholamines, carcinoembryonic antigen cell adhesion molecule 8 (CEACAM8), and IFN-? caused differentiation of IgM+IgD+CD27+ B cells into PCs, induced class switching to IgG2, and was reproducible in cocultures with neutrophils. In conclusion, this study substantiates memory B-cell characteristics of human IgM+IgD+CD27+ B cells in that they share typical memory B-cell transcription patterns with IgG+ post-GC B cells and show a faster and more vigorous restimulation potential, a hallmark of immune memory. Moreover, this work reveals a functional plasticity of human IgM memory B cells by showing their propensity to undergo secondary GC reactions upon reactivation, but also by their special role in early inflammation via interaction with immunomodulatory neutrophils. PMID:25624468

  8. Aberrant levels of natural IgM antibodies in osteoarthritis and rheumatoid arthritis patients in comparison to healthy controls.

    PubMed

    Nguyen, Tue G; McKelvey, Kelly J; March, Lyn M; Hunter, David J; Xue, Meilang; Jackson, Christopher J; Morris, Jonathan M

    2016-02-01

    Natural IgM antibodies (nIgM) are polyreactive autoantibodies that have diverse roles in regulating autoimmunity, systemic inflammation and removal of oxidized low-density lipoproteins (oxLDL). We hypothesized that aberrant states of nIgM may exist in persons with osteoarthritis (OA) and rheumatoid arthritis (RA). Herein, we characterized and compared the levels of nIgM specific for phosphorylcholine (anti-PC), double-stranded DNA (anti-dsDNA), and galactosyl (anti-Gal) in persons with OA, RA and healthy controls (HC). Levels of anti-PC nIgM in OA patients were significantly lower than both HC and RA patients in an age-adjusted analysis (P<0.05). In contrast, anti-Gal nIgM levels were significantly higher in RA patients than OA patients (P<0.05) and markedly increased in comparison to HC. Anti-PC nIgM significantly correlated with anti-dsDNA and anti-Gal nIgM levels in HC and RA (P<0.05) but not in OA patients. Elevated CRP levels were associated with RA conditions and old ages in general. There was no significant correlation between anti-PC nIgM and CRP or oxLDL levels. Our study highlights for the first time the evidence of aberrant state of nIgM in human OA compared to healthy individuals that implicates a deficiency in immune responses to oxLDL which may contribute to the metabolic syndromes in the development of OA. PMID:26744098

  9. Serological Profile of HSV-2 in STD Patients: Evaluation of Diagnostic Utility of HSV-2 IgM and IgG Detection

    PubMed Central

    Rashetha; Sucilathangam, G.; Cinthujah, B.; Revathy, C.

    2014-01-01

    Background and Objectives:The present study was undertaken to determine Herpes Simplex Virus-2 seroprevalence in sexually active adults aged 20-49 and to investigate the correlation with sociodemographic characteristics and to find its association with other sexually transmitted diseases especially HIV and also to assess the proportion of primary and reactivated HSV-2 cases. Materials and Methods:This prospective study was carried out for a period of six months in a tertiary care hospital. Serum samples were taken from 91 patients attending the out Patient clinic of the Department of Venereology. The serological testing for HSV-2 was performed on all the specimens by using Euroimmun anti-HSV2 (gG2) IgM ELISA and IgG ELISA. Results: Out of the 91 STD patients in the study group, 18 males (34.62%) and 14 females (36.84%) tested positive for HSV-2 antibodies. Seropositivity rate is 35.16%. More number of HSV-2 positive cases were seen among males, older age, rural residence, low socioeconomic status, single marital status, irregular condom usage during the sexual intercourses with new partners and with higher number of sexual partners during lifetime. HSV-2 IgM alone was positive in three cases, HSV-2 IgG alone was positive in 26 cases and three had a positive HSV-2 IgM and IgG result. Addition of IgM testing increased rate of detecting seroconversion, 31.87%, when only IgG ELISA was used, to 35.16 % patients when IgM test was added. In the study group four cases tested positive for VDRL, and one of them was a known positive case. Among the 55 HIV positive cases in the study group, HSV 2 was positive in 17 cases and among the 36 HIV negative cases HSV 2 was positive in 15 cases. (30.91% and 47.22%).Though the number of HIV cases were high, HSV 2 positivity among them was statistically not significant. Conclusion:The purpose of screening for HSV-2 is not only to identify seropositivity, but to help seropositive people identify symptoms and protect themselves from acquiring HIV and to protect their partners and seronegative people from acquiring HSV-2 and/or HIV. PMID:25653947

  10. Dried Blood Spots versus Sera for Detection of Rubella Virus-Specific Immunoglobulin M (IgM) and IgG in Samples Collected during a Rubella Outbreak in Peru▿

    PubMed Central

    Helfand, Rita F.; Cabezas, Cesar; Abernathy, Emily; Castillo-Solorzano, Carlos; Ortiz, Ana Cecilia; Sun, Hong; Osores, Fernando; Oliveira, Lucia; Whittembury, Alvaro; Charles, Myrna; Andrus, Jon; Icenogle, Joe

    2007-01-01

    Most persons with rubella virus-specific immunoglobulin M (IgM)- or IgG-positive sera tested positive (98% [n = 178] and 99% [n = 221], respectively) using paired filter paper dried blood spot (DBS) samples, provided that DBS indeterminate results were called positive. For persons with IgM- or IgG-negative sera, 97% and 98%, respectively, were negative using DBS. PMID:17881506

  11. B cell-intrinsic toll-like receptor 7 is responsible for the enhanced anti-PEG IgM production following injection of siRNA-containing PEGylated lipoplex in mice.

    PubMed

    Hashimoto, Yosuke; Abu Lila, Amr S; Shimizu, Taro; Ishida, Tatsuhiro; Kiwada, Hiroshi

    2014-06-28

    Recently, we reported that immunostimulatory siRNA-containing PEGylated lipoplex (PEGylated siRNA-lipoplex) activates the immune system, resulting in the enhanced production of anti-PEG IgM. However, the enhancing mechanism upon anti-PEG IgM production has not been fully elucidated. In this study, we employed toll-like receptor 7 knock out (TLR7 KO) mice, and showed how PEGylated siRNA-lipoplex activates the innate immune system through TLR7 and consequently enhances anti-PEG IgM production. In addition, we showed that SCID mice reconstituted with TLR7-deficient B cells failed to enhance anti-PEG IgM production following the injection of PEGylated siRNA-lipoplex, but that SCID mice reconstituted with wild type B cells did enhance anti-PEG IgM production. These results suggest that immune activation via B cell-intrinsic TLR7, but not other TLR7-expressing cells, contributes predominantly to an enhanced anti-PEG IgM production in response to the intravenous injection of PEGylated siRNA-lipoplexes. A strategy to evade B cell-intrinsic TLR7 activation by siRNA, such as chemical modification, may overcome immunological barriers to PEGylated liposome-based siRNA therapeutics. PMID:24727075

  12. Diagnosis of Leptospirosis: Comparison between Microscopic Agglutination Test, IgM-ELISA and IgM Rapid Immunochromatography Test

    PubMed Central

    Niloofa, Roshan; Fernando, Narmada; de Silva, Nipun Lakshitha; Karunanayake, Lilani; Wickramasinghe, Hasith; Dikmadugoda, Nandana; Premawansa, Gayani; Wickramasinghe, Rajitha; de Silva, H. Janaka; Premawansa, Sunil; Rajapakse, Senaka; Handunnetti, Shiroma

    2015-01-01

    Background Leptospirosis is diagnosed on clinical grounds, and confirmed by microscopic agglutination test (MAT). IgM-ELISA (Serion-Virion) and immunochromatography test (Leptocheck-WB) are two immunodiagnostic assays for leptospirosis. Their sensitivity, specificity and applicability in Sri Lanka have not been systematically evaluated. Methods Clinically diagnosed leptospirosis patients (n = 919) were recruited from three hospitals in the Western Province of Sri Lanka, during June 2012 to December 2013. MAT, IgM-ELISA and Leptocheck-WB were performed on all patient sera. MAT titer of ≥400 in single sample, four-fold rise or seroconversion ≥100 in paired samples were considered as positive for MAT. For diagnostic confirmation, MAT was performed during both acute and convalescent phases. Anti-leptospiral IgM ≥20 IU/ml and appearance of a band in the test window were considered as positive for IgM-ELISA and Leptocheck-WB test respectively. Patients with an alternative diagnosis (n = 31) were excluded. Data analysis was performed using two methods, i) considering MAT as reference standard and ii) using Bayesian latent class model analysis (BLCM) which considers each test as imperfect. Results MAT, IgM-ELISA and Leptocheck-WB positivity were 39.8%, 45.8% and 38.7% respectively during the acute phase. Acute-phase MAT had specificity and sensitivity of 95.7% and 55.3% respectively, when compared to overall MAT positivity. IgM-ELISA and Leptocheck-WB had similar diagnostic sensitivity when compared with acute-phase MAT as the gold standard, although IgM-ELISA showed higher specificity (84.5%) than Leptocheck-WB (73.3%). BLCM analysis showed that IgM-ELISA and Leptocheck-WB had similar sensitivities (86.0% and 87.4%), while acute-phase MAT had the lowest sensitivity (77.4%). However, acute-phase MAT had high specificity (97.6%), while IgM-ELISA and Leptocheck-WB showed similar but lower specificity (84.5% and 82.9%). Conclusions Both IgM-ELISA and Leptocheck-WB shows similar sensitivities and specificities. IgM-ELISA may be superior to MAT during the acute phase and suitable for early diagnosis of leptospirosis. Leptocheck-WB is suitable as a rapid immunodiagnostic screening test for resource limited settings. PMID:26086800

  13. Further evaluation of the characteristics of Treponema pallidum-specific IgM antibody in syphilis serofast reaction patients.

    PubMed

    Lin, Li-Rong; Zheng, Wei-Hong; Tong, Man-Li; Fu, Zuo-Gen; Liu, Gui-Li; Fu, Jian-Guo; Zhang, Dai-Wei; Yang, Tian-Ci; Liu, Li-Li

    2011-11-01

    Syphilis serofast reaction (SSR) is common in clinical work. From June 2005 to May 2009, 1208 syphilis patients were chosen for research by the Xiamen Center of Clinical Laboratory in China. Serologic tests were performed with toluidine red unheated serum test (TRUST) and Treponema pallidum particle agglutination (TPPA). Then, T. pallidum-specific IgM antibody (TP-IgM) was detected with fluorescent treponemal antibody absorption (FTA-Abs) and TPPA. In this study, patients were divided into the following experimental groups according to the results of TRUST and TPPA: (1) the SSR group consisted of 411 cases with (+) TRUST and (+) TPPA, and without clinical manifestations after 1 year of recommended syphilis treatment; (2) the serum cure group, which was further subdivided into group A consisting of 251cases with (-) TRUST and (+) TPPA; (3) group B consisting of 546 cases with (-) TRUST and (-) TPPA; and (4) the blood donor control group which consisted of 100 cases. We demonstrated that a total of 136 cases (33.09%) of 411 SSR patients were TP-IgM positive by TPPA, and this percentage was markedly higher than that in serum cure group A (9.16%). FTA-Abs analyses revealed similar results. All samples in serum cure group B and the control group were TP-IgM negative, which is identical to our previous report. The present study also indicated that the TP-IgM positive rate was not significantly different among patients with different ages, genders, and clinical phases after 1 year of recommended therapy. From the total of 1208 syphilis patients, 289 were randomly selected for TP-DNA detection by fluorescence quantitative polymerase chain reaction, and the positive rate of TP-DNA was 32.53%, which was slightly higher than that of FTA-Abs TP-IgM, and no statistically significant difference by chi-square tests, indicating the TP-DNA result is preferably consistent with FTA-Abs and supporting our deduction that TP-IgM could be used as a serologic marker for the relapse and infection of syphilis. PMID:21899981

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

    PubMed Central

    Vojdani, Aristo

    2009-01-01

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

  15. Single or combined effects of Lactobacillus sakei and inulin on growth, non-specific immunity and IgM expression in leopard grouper (Mycteroperca rosacea).

    PubMed

    Reyes-Becerril, Martha; Ascencio, Felipe; Gracia-Lopez, Vicente; Macias, Ma Esther; Roa, Marcos Cadena; Esteban, María Ángeles

    2014-08-01

    The aim of this study was to evaluate the single or combined effects of Lactobacillus sakei with inulin suitable for immunological in vivo studies in farmed fish. By in vitro assays, L. sakei strain 5-4 showed antibacterial activities against all assayed fish pathogens (except the Vibrio harveyi strain CAIM-1793). L. sakei was able to survive at high fish bile concentrations. Fermentation of the agave inulin resulted in a large increase in number of lactobacilli. For the in vivo study, fish were fed for 8 weeks four practical diets: control diet (control), L. sakei 5-4 (10(7) CFU/g), inulin (1% or 10 g/kg) and L. sakei + inulin (10(7) CFU/g + 10 g/kg). The weight gain showed clearly the synergistic effect of L. sakei 5-4 and inulin at 6 and 8 weeks of treatments. Leopard grouper fed with L. sakei alone or combined with inulin have significantly increased the assayed physiological and humoral immune parameters. By real-time PCR assays, the mRNA transcripts of immunoglobulin M (IgM) were found to be higher expressed in intestine, head kidney, mucus, gill, spleen and skin. Moreover, mRNA expression levels of IgM in head kidney and anterior intestine were measured by real-time PCR. L. sakei 5-4 and L. sakei + inulin supplemented diet up-regulated the expression of IgM at week 4 and 8 in intestine and head kidney, respectively. These results support the idea that the L. sakei 5-4 alone or combined with agave inulin improved growth performance and stimulates the immune system of leopard grouper. PMID:24464476

  16. Identification of Cell Surface Straight Chain Poly-N-Acetyl-Lactosamine Bearing Protein Ligands for VH4-34-Encoded Natural IgM Antibodies.

    PubMed

    Bhat, Neelima M; Adams, Christopher M; Chen, Yi; Bieber, Marcia M; Teng, Nelson N H

    2015-12-01

    B cell binding and cytotoxicity by human VH4-34-encoded Abs of the IgM isotype has been well documented. A VH4-34-IgM has recently shown a favorable early response in a phase 1 trial for treatment of B cell acute lymphoblastic leukemia. Although its B cell ligand has been identified as straight chain poly-N-acetyl-lactosamine (SC-PNAL), the carrier of the sugar moiety has not been identified. Using nanoelectrospray ionization mass spectrometry, we identify the metabolic activation related protein complex of CD147-CD98 as a major carrier of poly-N-acetyl-lactosamine (SC-PNAL) on human pre-B cell line Nalm-6. Previous studies have suggested CD45 as the SC-PNAL carrier for VH4-34-encoded IgG Abs. Because Nalm-6 is CD45 negative, human peripheral blood B lymphocytes and human B cell line, Reh, with high CD45 expression, were examined for SC-PNAL carrier proteins. Western blot analysis shows that the CD147-98 complex is indeed immunoprecipitated by VH4-34-encoded IgMs from human peripheral blood B lymphocytes and human B cell lines, Reh, OCI-Ly8, and Nalm-6. However, CD45 is immunoprecipitated only from peripheral B lymphocytes, but not from Reh despite the high expression of CD45. These results suggest that human B cells retain SC-PNAL on the CD147-98 complex, but modulate the sugar moiety on CD45. Because the carbohydrate moiety may act as a selecting Ag for VH4-34 autoantibody repertoire, its differential expression on proteins may provide a clue to the intricate atypical regulation of the VH4-34 gene. PMID:26503955

  17. Diagnostic Accuracy of the InBios Scrub Typhus Detect Enzyme-Linked Immunoassay for the Detection of IgM Antibodies in Northern Thailand

    PubMed Central

    Blacksell, Stuart D.; Tanganuchitcharnchai, Ampai; Nawtaisong, Pruksa; Kantipong, Pacharee; Laongnualpanich, Achara; Day, Nicholas P. J.

    2015-01-01

    In this study, we examined the diagnostic accuracy of the InBios Scrub Typhus Detect IgM enzyme-linked immunosorbent assay (ELISA) and determined the optimal diagnostic optical density (OD) cutoffs for screening and diagnostic applications based on prospectively collected, characterized samples from undifferentiated febrile illness patients in northern Thailand. Direct comparisons with the serological gold standard, indirect immunofluorescence assay (IFA), revealed strong statistical correlation of ELISA OD values and IFA IgM titers. Determination of the optimal ELISA cutoff for seroepidemiology or screening purposes compared to the corresponding IFA reciprocal titer of 400 as previously described for Thailand was 0.60 OD, which corresponded to a sensitivity (Sn) of 84% and a specificity (Sp) of 98%. The diagnostic performance against the improved and more-stringent scrub typhus infection criteria (STIC), correcting for low false-positive IFA titers, resulted in an Sn of 93% and an Sp of 91% at an ELISA cutoff of 0.5 OD. This diagnostic ELISA cutoff corresponds to IFA reciprocal titers of 1,600 to 3,200, which greatly reduces the false-positive rates associated with low-positive IFA titers. These data are in congruence with the recently improved serodiagnostic positivity criteria using the Bayesian latent class modeling approach. In summary, the InBios Scrub Typhus Detect IgM ELISA is affordable and easy-to-use, with adequate diagnostic accuracy for screening and diagnostic purposes, and should be considered an improved alternative to the gold standard IFA for acute diagnosis. For broader application, regional cutoff validation and antigenic composition for consistent diagnostic accuracy should be considered. PMID:26656118

  18. Seroprevalence of IgG and IgM antibodies and associated risk factors for toxoplasmosis in cats and dogs from sub-tropical arid parts of Pakistan.

    PubMed

    Ahmad, N; Ahmed, H; Irum, S; Qayyum, M

    2014-12-01

    Pet cats and dogs are an important source of human toxoplasmosis because of their intimate relationship with humans. Present study was designed to determine the prevalence and risk factors of toxoplasmosis in cats and dogs in northern sub-tropical arid region of Pakistan where no such work has been previously conducted. For this study 420 cats and 408 dogs visiting different pet clinics and veterinary hospitals were screened for the presence of anti-Toxoplasma IgG and IgM antibodies using ELISA technique. Epidemiological information regarding age, sex, area, outdoor access and hunting practice was obtained from the owners by questionnaire interview. Overall seroprevalence in cats and dogs was 26.43% (111/420) and 28.43% (116/408) respectively. IgG antibodies were found in 23.33% (98) cats and 25.49% (104) dogs while IgM antibodies were found in 3.57% (15) cats and 3.92% (16) dogs. Seroprevalence was significantly high in cats and dogs older than one year. No significant difference was recorded between males and females. Cats and dogs from rural areas showed higher prevalence. Dogs which had access to outside also showed high seroprevalence. The present study indicates that Toxoplasma gondii is widespread in pet animals in Pakistan which may have important implication for public health. PMID:25776604

  19. Development and validation of radioligand binding assays to measure total, IgA, IgE, IgG, and IgM insulin antibodies in human serum.

    PubMed

    Moxness, MichaeI; Foley, Jim; Stene, Mark; Finco-Kent, Deborah; Bedian, Vahe; Krasner, Alan; Kawabata, Thomas

    2003-11-01

    Radioligand binding assays for total and Ig classes of insulin antibodies (IAB) were developed and validated. For each assay, insulin-extracted serum samples were incubated with radiolabeled insulin in the presence and absence of high levels of unlabeled insulin to determine nonspecific binding and total binding, respectively. To measure total IAB, antibody-bound insulin was precipitated with a polyethylene glycol solution, washed, and counted in a gamma-counter. To measure IgG IAB, samples were treated with protein G-Sepharose beads, centrifuged, washed, and counted. For the measurement of IgA, IgE, and IgM IAB, IgG was removed from the samples and treated with anti-IgA, -IgE, or -IgM conjugated to Sepharose beads, centrifuged, washed, and counted. The acid/charcoal extraction of bound and unbound insulin from serum samples was optimized. Specificity and binding capacity of the protein G and antibody-bound beads were evaluated and optimized. The linear region of the total and IgG IAB assays was determined using serum samples containing high levels of insulin antibodies. The limit of quantitation, limit of detection, and precision for all the assays were also determined. PMID:14679073

  20. A somatically mutated human antiganglioside IgM antibody that induces experimental neuropathy in mice is encoded by the variable region heavy chain gene, V1-18.

    PubMed

    Willison, H J; O'Hanlon, G M; Paterson, G; Veitch, J; Wilson, G; Roberts, M; Tang, T; Vincent, A

    1996-03-01

    IgM paraproteins associated with autoimmune peripheral neuropathy and anti-Pr cold agglutinins react with sialic acid epitopes present on disialylated gangliosides including GD1b, GT1b, GQ1b, and GD3. A causal relationship between the paraprotein and the neuropathy has never been proven experimentally. From peripheral blood B cells of an affected patient, we have cloned a human hybridoma secreting an antidisialosyl IgM mAb, termed Ha1, that shows identical structural and functional characteristics to its serum counterpart. Variable region analysis shows Ha1 is encoded by the same VH1 family heavy chain gene, V1-18, as the only other known anti-Pr antibody sequence and is somatically mutated, suggesting that it [correction of is] arose in vivo in response to antigenic stimulation. In the rodent peripheral nervous system, Ha1 immunolocalizes to dorsal root ganglia, motor nerve terminals, muscle spindles, myelinated axons, and nodes of Ranvier. After intraperitoneal injection of affinity-purified antibody into mice for 10 d, electrophysiological recordings from the phrenic nerve-hemidiaphragm preparation demonstrated impairment of nerve excitability and a reduction in quantal release of neurotransmitter. These data unequivocally establish that an antidisialosyl antibody can exert pathophysiological effects on the peripheral nervous system and strongly support the view that the antibody contributes to the associated human disease. PMID:8636426

  1. Terminal carbohydrate composition, IgM level and enzymatic and bacteriostatic activity of European sea bass (Dicentrarchus labrax) skin epidermis extracts.

    PubMed

    Guardiola, Francisco A; de Haro, Juan P; Daz-Baos, Francisco Guillermo; Meseguer, Jos; Cuesta, Alberto; Esteban, M ngeles

    2015-11-01

    Although the skin is one of the main defense barriers of fish to date, very little is known about the immune implications and the properties of the numerous substances present in skin cells. In the present study, terminal carbohydrate composition and some components of the skin immunity (total IgM level, and several enzymatic and bacteriostatic activities) present on aqueous and organic epidermal extracts of European sea bass (Dicentrarchus labrax) were determined. Most of the parameters measured followed a protein concentration dose-response. Curiously, both skin extracts have similar levels of total IgM. However, aqueous extracts showed higher presence of some terminal carbohydrates, alkaline phosphatase and esterase activities and lower proteases and ceruloplasmin activities than epidermal organic extracts. Regarding the bacteriostatic activity, the growth of all the bacterial strains tested was reduced when cultivated in presence of organic extracts, being the observed reduction correlated to the protein concentration present in the extract sample. On the contrary, skin aqueous extracts have no significant effect on bacterial growth or even allow bacteria to overgrow, suggesting that the bacteria could use the extracts as a nutrient source. The results are discussed and compared with the same activities studied on fish skin mucus in order to understand their possible implications on mucosal immunity. PMID:26384845

  2. Reference Intervals for Serum Immunoglobulins IgG, IgA, IgM and Complements C3 and C4 in Iranian Healthy Children

    PubMed Central

    Kardar, GA; Oraei, M; Shahsavani, M; Namdar, Z; Kazemisefat, GE; Haghi Ashtiani, MT; Shams, S; Pourpak, Z; Moin, M

    2012-01-01

    Background: Determination of reference ranges of each serum protein in normal population of each country is required for studies and clinical interpretation. The aim of this study was defining reference range values of immunoglobulins and complement components in Iranian healthy children. Methods: This study was conducted from June 2003 to June 2006 in Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences. Serum levels of IgG, IgM, IgA, C3 and C4 in 800 Iranian healthy children from newborn to 18 years of age in four population were measured by nephelometry. Kolmogrov-Smirnov tests and Pearson correlation tests were used for analysis. Results: Our results mainly agree with previous reports, except for some discrepancy that might be due to the ethnic and geographic variety. There was a significant difference between two sexes only with IgA in the group of 13 months old, which was higher in male group and IgM in groups of 35, 68 and 911 years old that were higher in female groups. Mean of other serum immunoglobulins and complements was not significantly different between male and female groups. Conclusion: These results can be considered as a local reference for use in laboratories, clinical interpretations, and research for Iranian children. PMID:23113211

  3. Generation of monoclonal antibodies against human recombinant interferon beta using genetic immunization with simultaneous expression of IgM and IgG isotypes.

    PubMed

    Cantelli, Carina Pacheco; da Glria Martins Teixeira, Maria; Santos, Eneida Almeida; da Silva, Haroldo Cid; da Silva E Mouta, Sergio; Pimenta, Marcia Maria Arajo; Vianna, Carlos Otvio Alves; de Souza, Natlia Plnio; Batoreu, Ndia Maria; Galler, Ricardo; de Moraes, Marcia Terezinha Baroni

    2009-06-01

    Monoclonal antibodies (MAbs) against human recombinant interferon beta (hrIFNbeta) were generated by genetic immunization (GI). In order to test two viral promoters frequently used in mammalian expression plasmid vectors, mice were inoculated four times by intramuscular injection, without adjuvant, with 100 microg of either pcDNA 3.1hrIFNbeta or pZeoSV2IFNbeta containing the entire human interferon beta gene and under the control of, respectively, human cytomegalovirus (HCMV) immediate-early promoter or early SV-40 enhancer/promoter. Only serum samples from mice immunized with pZeoSV2IFNbeta were positive to anti-hrIFNbeta. The spleens of the immunized mice were fused with myeloma Sp2/0 cells and the hybridoma clones generated screened by an in house enzyme-linked immunosorbent assay (ELISA). Fourteen MAbs were selected as reactive with hrIFNbeta. Western blot analysis was performed and only one recognized the 18 kDa isoform (non-glycosylated) of hrIFNbeta. All MAbs were subjected to antibody isotype characterization with a commercial ELISA and showed unusual profile with simultaneous expression of both IgM and IgG2a isotypes. This observation is further supported by RT-PCR amplification of the IgM CH4 domain using total RNA from hybridomas. PMID:19519248

  4. Kinetics of dengue non-structural protein 1 antigen and IgM and IgA antibodies in capillary blood samples from confirmed dengue patients.

    PubMed

    Matheus, Sverine; Pham, Thai Binh; Labeau, Bhetty; Huong, Vu Thi Que; Lacoste, Vincent; Deparis, Xavier; Marechal, Vincent

    2014-03-01

    Large-scale epidemiological surveillance of dengue in the field and dengue patient management require simple methods for sample collection, storage, and transportation as well as effective diagnostic tools. We evaluated the kinetics of three biological markers of dengue infection-non-structural protein 1 (NS1) antigen, immunoglobulin M (IgM), and IgA-in sequential capillary blood samples collected from fingertips of confirmed dengue patients. The overall sensitivities and specificities of the tests were 96% and 100%, respectively, for NS1, 58.1% and 100%, respectively, for IgM, and 33% and 100%, respectively, for IgA. During the acute phase of the disease, NS1 was the best marker of dengue infection, with a sensitivity of 98.7%, whereas from day 5, all three markers exhibited relevant levels of sensitivity. This first descriptive study of the kinetics of biological markers of dengue in capillary blood samples confirms the usefulness of this biological compartment for dengue diagnosis and argues for its exploitation in community-level and remote settings. PMID:24470561

  5. PROBING THE IGM/GALAXY CONNECTION. IV. THE LCO/WFCCD GALAXY SURVEY OF 20 FIELDS SURROUNDING UV-BRIGHT QUASARS

    SciTech Connect

    Prochaska, J. Xavier; Chen, H.-W.; Cooksey, K. L.; Mulchaey, J. S. E-mail: bjw@as.arizona.edu E-mail: kcooksey@space.mit.edu

    2011-04-01

    We publish the survey for galaxies in 20 fields containing ultraviolet bright quasars (with z{sub em} {approx} 0.1-0.5) that can be used to study the association between galaxies and absorption systems from the low-z intergalactic medium (IGM). The survey is magnitude limited (R {approx} 19.5 mag) and highly complete out to 10' from the quasar in each field. It was designed to detect dwarf galaxies (L {approx} 0.1L*) at an impact parameter {rho} {approx} 1 Mpc (z = 0.1) from a quasar. The complete sample (all 20 fields) includes R-band photometry for 84,718 sources and confirmed redshifts for 2800 sources. This includes 1198 galaxies with 0.005 < z < (z{sub em} - 0.01) at a median redshift of 0.18, which may associated with IGM absorption lines. All of the imaging was acquired with cameras on the Swope 40'' telescope and the spectra were obtained via slit mask observations using the WFCCD spectrograph on the Dupont 100'' telescope at Las Campanas Observatory. This paper describes the data reduction, imaging analysis, photometry, and spectral analysis of the survey. We tabulate the principal measurements for all sources in each field and provide the spectroscopic data set online.

  6. Validation of the Dri-Dot Latex agglutination and IgM lateral flow assays for the diagnosis of typhoid fever in an Egyptian population.

    PubMed

    Nakhla, Isabelle; El Mohammady, Hanan; Mansour, Adel; Klena, John D; Hassan, Khaled; Sultan, Yehia; Pastoor, Rob; Abdoel, Theresia H; Smits, Henk

    2011-08-01

    Laboratory confirmation of typhoid fever is essential for appropriate medical treatment. Blood culture is a standard test for diagnosis of typhoid fever, but well-equipped diagnostic facilities to perform culture are seldom available in endemic areas. We retrospectively compared 2 diagnostic field tests, a latex agglutination Dri-Dot assay and an IgM Lateral Flow assay, to blood culture, in patients with clinically diagnosed typhoid fever. Sensitivity of the Dri-Dot was 71.4%, and specificity was 86.3% for samples collected at time of first diagnosis. Sensitivity and specificity of IgM Lateral Flow were 80% and 71.4%, respectively. A major limitation of these serologic tests is the limited sensitivity at the early stage of the disease. Performing both tests in parallel increased sensitivity to 84.3%, but decreased specificity to 70.5%. There was a trend towards improved diagnostic performance using either assay over a longer duration of illness. These rapid, point-of-care assays for typhoid fever provide easy-to-interpret results in typhoid-endemic countries and may be most useful in patients presenting 1 week after symptom onset. PMID:21658878

  7. Seroprevalence of anti-Toxoplasma IgG and IgM among individuals who were referred to medical laboratories in Mazandaran province, northern Iran.

    PubMed

    Sharif, Mehdi; Daryani, Ahmad; Ebrahimnejad, Zahra; Gholami, Shirzad; Ahmadpour, Ehsan; Borhani, Samaneh; Lamsechi, Narges

    2016-01-01

    Toxoplasma gondii (T. gondii) is a protozoan parasite that can cause toxoplasmosis in humans. However, there is no current data regarding Toxoplasma infection among individuals who were referred to medical laboratories in Mazandaran province (northern Iran). Therefore, we performed a population-based study of Toxoplasma seroprevalence in this region. A total of 1832 sera samples (from 654 men and 1178 women) were collected from people who were referred to medical laboratories in different cities throughout Mazandaran province between March and July 2012. The serum titers of anti-T. gondii IgG and IgM were measured using enzyme-linked immunosorbent assays. The seroprevalence of anti-Toxoplasma IgG was 55.5%; and 14.4% of the positive samples were seropositive for anti-Toxoplasma IgM. The highest seroprevalence was observed among people who were >50 years old (90.6%), and the lowest seroprevalence was observed among children who were 0-9 years old (9.4%; P<0.001). There was no significant difference in the seroprevalences for each sex in the study population. However, a regional sex-specific difference in seroprevalence was observed between men (54.1%) and women (70.6%; P=0.003) in the western cities of Mazandaran. As the seroprevalence of T. gondii in western and eastern Mazandaran was higher than that in the central cities, there is a need to evaluate the nature of the infection chain in these areas. PMID:26159578

  8. Shielding of a lipooligosaccharide IgM epitope allows evasion of neutrophil-mediated killing of an invasive strain of nontypeable Haemophilus influenzae.

    PubMed

    Langereis, Jeroen D; Weiser, Jeffrey N

    2014-01-01

    Nontypeable Haemophilus influenzae is a frequent cause of noninvasive mucosal inflammatory diseases but may also cause invasive diseases, such as sepsis and meningitis, especially in children and the elderly. Infection by nontypeable Haemophilus influenzae is characterized by recruitment of neutrophilic granulocytes. Despite the presence of a large number of neutrophils, infections with nontypeable Haemophilus influenzae are often not cleared effectively by the antimicrobial activity of these immune cells. Herein, we examined how nontypeable Haemophilus influenzae evades neutrophil-mediated killing. Transposon sequencing (Tn-seq) was used on an isolate resistant to neutrophil-mediated killing to identify genes required for its survival in the presence of human neutrophils and serum, which provided a source of complement and antibodies. Results show that nontypeable Haemophilus influenzae prevents complement-dependent neutrophil-mediated killing by expression of surface galactose-containing oligosaccharide structures. These outer-core structures block recognition of an inner-core lipooligosaccharide epitope containing glucose attached to heptose HepIII-?1,2-Glc by replacement with galactose attached to HepIII or through shielding HepIII-?1,2-Glc by phase-variable attachment of oligosaccharide chain extensions. When the HepIII-?1,2-Glc-containing epitope is expressed and exposed, nontypeable Haemophilus influenzae is opsonized by naturally acquired IgM generally present in human serum and subsequently phagocytosed and killed by human neutrophils. Clinical nontypeable Haemophilus influenzae isolates containing galactose attached to HepIII that are not recognized by this IgM are more often found to cause invasive infections. Importance: Neutrophils are white blood cells that specialize in killing pathogens and are recruited to sites of inflammation. However, despite the presence of large numbers of neutrophils in the middle ear cavity and lungs of patients with otitis media or chronic obstructive pulmonary disease, respectively, the bacterium nontypeable Haemophilus influenzae is often not effectively cleared from these locations by these immune cells. In order to understand how nontypeable Haemophilus influenzae is able to cause inflammatory diseases in the presence of neutrophils, we determined the mechanism that underlies resistance to neutrophil-mediated killing. We have shown that nontypeable Haemophilus influenzae prevents binding of antibodies of the IgM subtype through changes in their surface lipooligosaccharide structure, thereby preventing complement activation and clearance by human neutrophils. PMID:25053788

  9. Progression From IgD+ IgM+ to Isotype-Switched B Cells Is Site Specific during Coronavirus-Induced Encephalomyelitis

    PubMed Central

    Phares, Timothy W.; DiSano, Krista D.; Stohlman, Stephen A.

    2014-01-01

    ABSTRACT Various infections in the central nervous system (CNS) trigger B cell accumulation; however, the relative dynamics between viral replication and alterations in distinct B cell subsets are largely unknown. Using a glia-tropic coronavirus infection, which is initiated in the brain but rapidly spreads to and predominantly persists in the spinal cord, this study characterizes longitudinal changes in B cell subsets at both infected anatomical sites. The phase of T cell-dependent, antibody-independent control of infectious virus was associated with a similar recruitment of naive/early-activated IgD+ IgM+ B cells into both the brain and spinal cord. This population was progressively replaced by CD138? IgD? IgM+ B cells, isotype-switched CD138? IgD? IgM? memory B cells (Bmem), and CD138+ antibody-secreting cells (ASC). A more rapid transition to Bmem and ASC in spinal cord than in brain was associated with higher levels of persisting viral RNA and transcripts encoding factors promoting B cell migration, differentiation, and survival. The results demonstrate that naive/early-activated B cells are recruited early during coronavirus CNS infection but are subsequently replaced by more differentiated B cells. Furthermore, viral persistence, even at low levels, is a driving force for accumulation of isotype-switched Bmem and ASC. IMPORTANCE Acute and chronic human CNS infections are associated with an accumulation of heterogeneous B cell subsets; however, their influence on viral load and disease is unclear. Using a glia-tropic coronavirus model, we demonstrate that the accumulation of B cells ranging from early-activated to isotype-switched differentiation stages is both temporally and spatially orchestrated. Acutely infected brains and spinal cords indiscriminately recruit a homogeneous population of early-activated B cells, which is progressively replaced by diverse, more differentiated subsets. The latter process is accelerated by elevated proinflammatory responses associated with viral persistence. The results imply that early-recruited B cells do not have antiviral function but may contribute to the inflammatory environment or act as antigen-presenting cells. Moreover, CNS viral persistence is a driving force promoting differentiated B cells with protective potential. PMID:24872583

  10. Molecular Cloning of a New Immunomodulatory Protein from Anoectochilus formosanus which Induces B Cell IgM Secretion through a T-Independent Mechanism

    PubMed Central

    Kuan, Yen-Chou; Wu, Tsai-Jen; Kuo, Che-Yu; Hsu, Ju-Chun; Chang, Wen-Ying; Sheu, Fuu

    2011-01-01

    An immunomodulatory protein (IPAF) was purified and cloned from Anoectochilus formosanus, an Orchidaceae herbal plant in Asia. The major targeting immune cells of IPAF and its modulating effects toward B lymphocytes were investigated. Rapid amplification of cDNA ends (RACE) was conducted to clone the IPAF gene, and the obtained sequence was BLAST compared on the NCBI database. MACS-purified mouse T and B lymphocytes were stimulated with IPAF and the cell proliferation, activation, and Igs production were examined. IPAF comprised a 25 amino acids signal peptide and a 138 amino acids protein which was homologous to the lectins from Orchidaceae plant. IPAF selectively induced the cell proliferation in mouse splenic B lymphocytes but not T lymphocytes. The IPAF-induced B cells exhibited increased CD69 and MHC class II expression, and a dose- and time-dependent enhancement in IgM production. These results suggested potential benefits of IPAF to strengthen the humoral immunity. PMID:21698210

  11. Variable region structure and staphylococcal protein A binding specificity of a mouse monoclonal IgM anti-laminin-receptor antibody.

    PubMed Central

    Feij, G C; Sabbaga, J; Carneiro, C R; Brgido, M M

    1997-01-01

    Staphylococcal protein A is a cell wall-attached polypeptide that acts as a B-lymphocyte superantigen. This activation correlates with specific VH gene segment usage in the B-cell receptor. B-cell receptor assembled from members of the VH3 family in humans, or S107 family in mice, has an intrinsic affinity for protein A. Human VH3-derived antibodies bind to domain D of protein A. We have characterized a mouse IgM monoclonal antibody that binds protein A. The sequencing of the variable region suggests an almost germline-encoded VH derived from S107 family and a V kappa 8-derived VL. The binding specificity of the monoclonal antibody was tested with various recombinant constructions derived from protein A. We show that, unlike human VH3-derived antibody, mouse S107-derived immunoglobulin binds to the B domain of the bacterial superantigen. PMID:9301540

  12. A monoclonal IgM kappa from a blood group B individual with specificity for alpha-galactosyl epitopes on partially hydrolyzed blood group B substance.

    PubMed

    Nickerson, K G; Liao, J; Kabat, E A

    1993-05-01

    We have characterized a human monoclonal IgM kappa, designated IgMDON, from a blood group B individual. IgMDON is specific for alpha-galactosyl residues on blood group B substance; its fine specificity as defined by hemagglutination, quantitative precipitin, and inhibition ELISA assays was for the defucosylated terminal Gal(alpha 1-3)Gal epitope. Gal(alpha 1-3)Gal epitopes are also found on a variety of normal and pathogenic intestinal bacteria, and polyclonal IgG antibodies with the same specificity are found in the serum of nearly all normal individuals. The specificity of IgMDON was also quite similar to that of a human antiserum, serum 262, obtained by immunizing an individual with blood group B substance that had been subjected to mild acid hydrolysis (BP1). The possible ways whereby IgMDON might have arisen are discussed. PMID:7688662

  13. Heterosubtypic Neutralizing Monoclonal Antibodies Cross-Protective against H5N1 and H1N1 Recovered from Human IgM+ Memory B Cells

    PubMed Central

    Throsby, Mark; van den Brink, Edward; Jongeneelen, Mandy; Poon, Leo L. M.; Alard, Philippe; Cornelissen, Lisette; Bakker, Arjen; Cox, Freek; van Deventer, Els; Guan, Yi; Cinatl, Jindrich; ter Meulen, Jan; Lasters, Ignace; Carsetti, Rita; Peiris, Malik; de Kruif, John; Goudsmit, Jaap

    2008-01-01

    Background The hemagglutinin (HA) glycoprotein is the principal target of protective humoral immune responses to influenza virus infections but such antibody responses only provide efficient protection against a narrow spectrum of HA antigenic variants within a given virus subtype. Avian influenza viruses such as H5N1 are currently panzootic and pose a pandemic threat. These viruses are antigenically diverse and protective strategies need to cross protect against diverse viral clades. Furthermore, there are 16 different HA subtypes and no certainty the next pandemic will be caused by an H5 subtype, thus it is important to develop prophylactic and therapeutic interventions that provide heterosubtypic protection. Methods and Findings Here we describe a panel of 13 monoclonal antibodies (mAbs) recovered from combinatorial display libraries that were constructed from human IgM+ memory B cells of recent (seasonal) influenza vaccinees. The mAbs have broad heterosubtypic neutralizing activity against antigenically diverse H1, H2, H5, H6, H8 and H9 influenza subtypes. Restriction to variable heavy chain gene IGHV1-69 in the high affinity mAb panel was associated with binding to a conserved hydrophobic pocket in the stem domain of HA. The most potent antibody (CR6261) was protective in mice when given before and after lethal H5N1 or H1N1 challenge. Conclusions The human monoclonal CR6261 described in this study could be developed for use as a broad spectrum agent for prophylaxis or treatment of human or avian influenza infections without prior strain characterization. Moreover, the CR6261 epitope could be applied in targeted vaccine strategies or in the design of novel antivirals. Finally our approach of screening the IgM+ memory repertoire could be applied to identify conserved and functionally relevant targets on other rapidly evolving pathogens. PMID:19079604

  14. Correlation of plasma viral loads and presence of Chikungunya IgM antibodies with cytokine/chemokine levels during acute Chikungunya virus infection.

    PubMed

    Reddy, Vijayalakshmi; Mani, Reeta Subramaniam; Desai, Anita; Ravi, Vasanthapuram

    2014-08-01

    Chikungunya (CHIKV) is an emerging arboviral infection of public health concern in India contributing to widespread morbidity. The precise molecular events occurring early in the infection have not been well understood. Cytokines/chemokines are suspected to play a key role in its pathogenesis. Very few studies have correlated the plasma levels of cytokines/chemokines with diagnostic markers such as viral loads and presence of CHIKV IgM antibodies. Understanding these dynamics in the early phase of CHIKV infection is likely to provide an insight into the evolution of the immune response, identify biomarkers for assessing severity, and for development of newer therapeutic strategies. This study was therefore undertaken to estimate the levels of various cytokines/chemokines in plasma samples of patients infected with CHIKV and correlate to viral load and CHIKV IgM antibodies. Cytokine/chemokine levels and viral loads in plasma were measured using cytometric bead array and TaqMan real time PCR assay, respectively. The findings revealed that acute phase of CHIKV infection is characterized by predominant inflammatory responses mediated by IL-6, IL-8, IP-10, MCP-1, and MIG (P?

  15. Shielding of a Lipooligosaccharide IgM Epitope Allows Evasion of Neutrophil-Mediated Killing of an Invasive Strain of Nontypeable Haemophilus influenzae

    PubMed Central

    Weiser, Jeffrey N.

    2014-01-01

    ABSTRACT Nontypeable Haemophilus influenzae is a frequent cause of noninvasive mucosal inflammatory diseases but may also cause invasive diseases, such as sepsis and meningitis, especially in children and the elderly. Infection by nontypeable Haemophilus influenzae is characterized by recruitment of neutrophilic granulocytes. Despite the presence of a large number of neutrophils, infections with nontypeable Haemophilus influenzae are often not cleared effectively by the antimicrobial activity of these immune cells. Herein, we examined how nontypeable Haemophilus influenzae evades neutrophil-mediated killing. Transposon sequencing (Tn-seq) was used on an isolate resistant to neutrophil-mediated killing to identify genes required for its survival in the presence of human neutrophils and serum, which provided a source of complement and antibodies. Results show that nontypeable Haemophilus influenzae prevents complement-dependent neutrophil-mediated killing by expression of surface galactose-containing oligosaccharide structures. These outer-core structures block recognition of an inner-core lipooligosaccharide epitope containing glucose attached to heptose HepIII-?1,2-Glc by replacement with galactose attached to HepIII or through shielding HepIII-?1,2-Glc by phase-variable attachment of oligosaccharide chain extensions. When the HepIII-?1,2-Glc-containing epitope is expressed and exposed, nontypeable Haemophilus influenzae is opsonized by naturally acquired IgM generally present in human serum and subsequently phagocytosed and killed by human neutrophils. Clinical nontypeable Haemophilus influenzae isolates containing galactose attached to HepIII that are not recognized by this IgM are more often found to cause invasive infections. PMID:25053788

  16. A potent neutralizing IgM mAb targeting the N218 epitope on E2 protein protects against Chikungunya virus pathogenesis.

    PubMed

    Lam, Shirley; Nyo, Min; Phuektes, Patchara; Yew, Chow Wenn; Tan, Yee Joo; Chu, Justin Jang Hann

    2015-11-01

    Chikungunya virus (CHIKV) is a medically important human viral pathogen that causes Chikungunya fever accompanied with debilitating and persistent joint pain. Host-elicited or passively-transferred monoclonal antibodies (mAb) are essential mediators of CHIKV clearance. Therefore, this study aimed to generate and characterize a panel of mAbs for their neutralization efficacy against CHIKV infection in a cell-based and murine model. To evaluate their antigenicity and neutralization profile, indirect enzyme-linked immunosorbent assay (ELISA), an immunofluorescence assay (IFA) and a plaque reduction neutralization test were performed on mAbs of IgM isotype. CHIKV escape mutants against mAb 3E7b neutralization were generated, and reverse genetics techniques were then used to create an infectious CHIKV clone with a single mutation. 3E7b was also administered to neonate mice prior or after CHIKV infection. The survival rate, CHIKV burden in tissues and histopathology of the limb muscles were evaluated. Both IgM 3E7b and 8A2c bind strongly to native CHIKV surface and potently neutralize CHIKV replication. Further analyses of 3E7b binding and neutralization of CHIKV single-mutant clones revealed that N218 of CHIKV E2 protein is a potent neutralizing epitope. In a pre-binding neutralization assay, 3E7b blocks CHIKV attachment to permissive cells, possibly by binding to the surface-accessible E2-N218 residue. Prophylactic administration of 3E7b to neonate mice markedly reduced viremia and protected against CHIKV pathogenesis in various mice tissues. Given therapeutically at 4h post-infection, 3E7b conferred 100% survival rate and similarly reduced CHIKV load in most mice tissues except the limb muscles. Collectively, these findings highlight the usefulness of 3E7b for future prophylactic or epitope-based vaccine design. PMID:26305993

  17. Natural IgM mediates complement-dependent uptake of Francisella tularensis by human neutrophils via CR1 and CR3 in nonimmune serum

    PubMed Central

    Schwartz, Justin T.; Barker, Jason H.; Long, Matthew E.; Kaufman, Justin; McCracken, Jenna; Allen, Lee-Ann H.

    2012-01-01

    A fundamental step in the life cycle of F. tularensis is bacterial entry into host cells. F. tularensis activates complement, and recent data suggest that the classical pathway is required for complement factor C3 deposition on the bacterial surface. Nevertheless, C3 deposition is inefficient and neither the specific serum components necessary for classical pathway activation by F. tularensis in nonimmune human serum, nor the receptors that mediate infection of neutrophils has been defined. Herein human neutrophil uptake of GFP-expressing F. tularensis strains LVS and Schu S4 was quantified with high efficiency by flow cytometry. Using depleted sera and purified complement components we demonstrated first that C1q and C3 were essential for F. tularensis phagocytosis whereas C5 was not. Second, we used purification and immuno-depletion approaches to identify a critical role for natural IgM in this process, and then used a wbtA2 mutant to identify LPS O-antigen and capsule as prominent targets of these antibodies on the bacterial surface. Finally, we demonstrate using receptor-blocking antibodies that CR1 (CD35) and CR3 (CD11b/CD18) acted in concert for phagocytosis of opsonized F. tularensis by human neutrophils, whereas CR3 and CR4 (CD11c/CD18) mediated infection of human monocyte-derived macrophages. Altogether, our data provide fundamental insight into mechanisms of F. tularensis phagocytosis and support a model whereby natural IgM binds to surface capsular and O-antigen polysaccharides of F. tularensis and initiates the classical complement cascade via C1q to promote C3-opsonization of the bacterium and phagocytosis via CR3 and either CR1 or CR4 in a phagocyte-specific manner. PMID:22888138

  18. Trends in the patterns of IgM and IgG antibodies in febrile persons with suspected dengue in Barbados, an English-speaking Caribbean country, 2006-2013.

    PubMed

    Kumar, Alok; Nielsen, Anders L

    2015-01-01

    Long-term seroprevalence studies of dengue have provided a measure of the degree of endemicity and future trends in disease prevalence and severity. In this study, we describe the seroprevalence of dengue antibodies in febrile persons with suspected acute dengue in Barbados. It is a retrospective population-based study of all febrile persons with suspected dengue from 2006 to 2013. All of the cases had IgM and IgG antibodies in the blood sample drawn between days 3 and 5 of their illness. Among the 8296 cases that were tested for IgM antibodies, 3037 (36.6%) had recent dengue infection. In the age groups <5 years, 5-20 years and >20 years, 23.3%, 39.6% and 35.5% had acute infection, respectively. Of the 7227 cases with documented IgG results, 5473 (75.7%) were positive and had a past infection. In the age groups <5 years, 5-20 years and >20 years, 31.2%, 65.2% and 86.6%, respectively, had a past infection (IgG positive). During the first 5 years of life, 10-20% of febrile persons investigated for dengue had a positive IgM and a negative IgG titer, between 5 and 10% had a positive IgM and IgG titer, 5% had a positive IgG and a negative IgM titer, and between 45% and 65% had a negative IgM and a negative IgG titer. Throughout the study period, between 12% and 20% of febrile persons failed to show any evidence of current or previous dengue. In the age groups <5 years, 5-20 years and >20 years, 45.0%, 18.8% and 7.2%, respectively, had no evidence of recent or past dengue (both IgM and IgG negative). Between 37% and 59% of the febrile persons had serological evidence of past dengue in the absence of any current dengue. In conclusion, the pattern of IgG antibodies in this study was comparable to those in countries known to be hyperendemic for dengue. The age of infection is likely to shift to younger adults and children who are more likely to have severe dengue in the future. PMID:26117708

  19. Relationship of IgG and IgM autoantibodies and immune complexes to oxidized LDL with markers of oxidation and inflammation and cardiovascular events: results from the EPIC-Norfolk Study.

    PubMed

    Ravandi, Amir; Boekholdt, S Matthijs; Mallat, Ziad; Talmud, Philippa J; Kastelein, John J P; Wareham, Nicholas J; Miller, Elizabeth R; Benessiano, Joelle; Tedgui, Alain; Witztum, Joseph L; Khaw, Kay-Tee; Tsimikas, Sotirios

    2011-10-01

    Levels of IgG and IgM autoantibodies (AA) to malondialdehyde (MDA)-LDL and apoB-immune complexes (ICs) were measured in 748 cases and 1,723 controls in the EPIC-Norfolk cohort and their association to coronary artery disease (CAD) events determined. We evaluated whether AA and IC modify CAD risk associated with secretory phospholipase A(2) (sPLA(2)) type IIA mass and activity, lipoprotein-associated PLA(2) activity, lipoprotein (a) [Lp(a)], oxidized phospholipids on apoB-100 (OxPL/apoB), myeloperoxidase, and high sensitivity C-reactive protein. IgG ICs were higher in cases versus controls (P = 0.02). Elevated levels of IgM AA and IC were inversely associated with Framingham Risk Score and number of metabolic syndrome criteria (p range 0.02-0.001). In regression analyses adjusted for age, smoking, diabetes, LDL-cholesterol, HDL-cholesterol, and systolic blood pressure, the highest tertiles of IgG and IgM AA and IC were not associated with higher risk of CAD events compared with the lowest tertiles. However, elevated levels of IgM IC reduced the risk of Lp(a) (P = 0.006) and elevated IgG MDA-LDL potentiated the risk of sPLA(2) mass (P = 0.018). This epidemiological cohort of initially healthy subjects shows that IgG and IgM AA and IC are not independent predictors of CAD events but may modify CAD risk associated with elevated levels of oxidative biomarkers. PMID:21821825

  20. Immunoglobulin (Ig)M antibodies against oxidized cardiolipin but not native cardiolipin are novel biomarkers in haemodialysis patients, associated negatively with mortality

    PubMed Central

    Frostegård, A G; Hua, X; Su, J; Carrero, J J; Heimbürger, O; Bárány, P; Stenvinkel, P; Frostegård, J

    2013-01-01

    The risk of premature death is high in haemodialysis (HD) patients. Antibodies against cardiolipin (anti-CL) are thrombogenic in diseases such as systemic lupus erythematosus (SLE). CL is easily oxidized (Ox) and plays a role in apoptosis. In this work we studied immunoglobulin (Ig)M anti-CL and anti-OxCL in HD-patients. We conducted an observational study with a prospective follow-up examining the relationship between anti-CL, anti-OxCL and mortality risk in a well-characterized cohort of 221 prevalent HD patients [56% men, median age 66 (interquartile range 51–74) years, vintage time 29 (15–58) months] with a mean follow-up period of 41 (20–48 months). According to the receiver operator characteristic (ROC) analysis, anti-OxCL [area under the curve (AUC) 0·62, P < 0·01], but not anti-CL (AUC 0·52, P = 0·2), is associated with mortality. In crude and adjusted Cox analysis, every log increase in anti-OxCL inversely predicted all-cause [adjusted hazard ratios (HR) 0·62 (0·43–0·89)] and CVD-related [adjusted HR 0·56 (0·32–0·98)] mortality. Patients with anti-OxCL levels below median also had increased all-cause and cardiovascular disease (CVD)-related mortality. Although anti-OxCL and anti-phosphorylcholine (PC) were related positively to each other (ρ = 0·57, P < 0·01), patients with one or two of these autoantibody levels below the median were associated with an incrementally increased death risk. Anti-OxCL were co-factor β2-GPI-independent; anti-CL from patients with anti-phospholipid antibody syndrome were β2-GPI-dependent, while sera from HD-patients less so. Sera from healthy donors was not β2-GPI-dependent. Anti-OxCL IgM is β2-glycoprotein 1 (GPI)-independent and a novel biomarker; low levels are associated with death among HD patients (and high levels with decreased risk). Combination with anti-PC increases this association. Putative therapeutic implications warrant further investigation. PMID:23879320

  1. Immunization of colorectal cancer patients with modified ovine submaxillary gland mucin and adjuvants induces IgM and IgG antibodies to sialylated Tn.

    PubMed

    O'Boyle, K P; Zamore, R; Adluri, S; Cohen, A; Kemeny, N; Welt, S; Lloyd, K O; Oettgen, H F; Old, L J; Livingston, P O

    1992-10-15

    Tn and sialylated Tn (sTn) are blood group-related epitopes expressed on mucins of colon carcinoma and other epithelial tumors and are, therefore, potential targets for immunological control. We have immunized 20 colorectal cancer patients at high risk for recurrence with a vaccine consisting of partially desialylated ovine submaxillary gland mucin (modified OSM) which contains both Tn and sTn determinants. Six patients were treated with modified OSM alone (group 1), eight patients were treated with modified OSM and the immunological adjuvant DETOX (group 2), and six patients were treated with modified OSM and Bacillus Calmette-Gurin (group 3). Pre- and postvaccination sera were tested by enzyme-linked immunosorbent assay and dot blot immune stains for antibodies reactive with modified OSM. Antibody titers increased in 4 of 8 patients immunized with modified OSM and DETOX, in 5 of 6 patients immunized with modified OSM and B. Calmette-Gurin, and in 0 of 6 patients receiving modified OSM without adjuvant. The specificity of induced IgM and IgG antibodies was confirmed by demonstrating reactivity with OSM, bovine submaxillary mucin, and synthetic glycoconjugates sTn-human serum albumin (HSA) and Tn-HSA in enzyme-linked immunosorbent assay and immune stains. Median IgM pre-postvaccination reciprocal titers were 20/80 for Tn-HSA and 10/320 for sTn-HSA. Low level IgG antibody titers against sTn-HSA were detected after vaccination in 7 patients. Toxicity was limited to inflammatory skin reactions at the site of vaccination resulting from the adjuvants. No inflammatory infiltrates were seen in the skin when the modified OSM vaccine was administered in the absence of an immunological adjuvant. These results demonstrate that sTn and Tn can be recognized by the human immune system and that vaccines containing these structures can be administered safely with immunological adjuvants. Attempts to augment the immunogenicity of these carbohydrate antigens by covalent attachment to immunogenic carrier proteins and the use of more potent immunological adjuvants are now being pursued. PMID:1394190

  2. Dengue virus infection induces broadly cross-reactive human IgM antibodies that recognize intact virions in humanized BLT-NSG mice.

    PubMed

    Jaiswal, Smita; Smith, Kenneth; Ramirez, Alejandro; Woda, Marcia; Pazoles, Pamela; Shultz, Leonard D; Greiner, Dale L; Brehm, Michael A; Mathew, Anuja

    2015-01-01

    The development of small animal models that elicit human immune responses to dengue virus (DENV) is important since prior immunity is a major risk factor for developing severe dengue disease. This study evaluated anti-DENV human antibody (hAb) responses generated from immortalized B cells after DENV-2 infection in NOD-scid IL2rγ(null) mice that were co-transplanted with human fetal thymus and liver tissues (BLT-NSG mice). DENV-specific human antibodies predominantly of the IgM isotype were isolated during acute infection and in convalescence. We found that while a few hAbs recognized the envelope protein produced as a soluble recombinant, a number of hAbs only recognized epitopes on intact virions. The majority of the hAbs isolated during acute infection and in immune mice were serotype-cross-reactive and poorly neutralizing. Viral titers in immune BLT-NSG mice were significantly decreased after challenge with a clinical strain of dengue. DENV-specific hAbs generated in BLT-NSG mice share some of the characteristics of Abs isolated in humans with natural infection. Humanized BLT-NSG mice provide an attractive preclinical platform to assess the immunogenicity of candidate dengue vaccines. PMID:25125497

  3. [Myopathy in patients with Waldenstrms macroglobulinemia. A case study and an overview of autoimmune expressions of type IgM monoclonal immunoglobulins].

    PubMed

    Adam, Zden?k; Kissov, Jarmila; Pour, Lud?k; Krej?, Marta; ev?kov, Eva; Koukalov, Renata; ?ermkov, Zde?ka; ?ern, Marta; Krl, Zden?k; Mayer, Ji?

    2015-09-01

    Waldenstrms macroglobulinemia which was manifested by muscle pain and anemia. The female patient had suffered from back pain for about 3 years before she came to our clinic. In the last year pain in the muscles of the upper and lower extremities developed in addition to back pain. This led to the suspicion of polymyositis. However this was not confirmed by a special examination. The patient was diagnosed with clearly established infiltration of lympho-plasmacytic lymphoma and 10.8 g/l of type IgM monoclonal immunoglobulin in the bone marrow. Serum myoglobin levels and serum CK activity were repeatedly significantly increased. Therefore the treatment with anti-CD20 monoclonal antibody (Mabthera) 375 mg/m2 i. v. was started, administered once a month, with cyclophosphamide 500 mg/m2 i. v. on days 1 and 15 of a 28-day cycle, and dexamethasone 20 mg from 1st through to 4th days and 15th through to 18th days of the treatment cycle. There were 8 cycles planned. Already after a 5th cycle, the disappearance of monoclonal immunoglobulin (negative immunofixation), normalisation of myoglobin and CK values and significant relief from muscle pain were achieved. The hemoglobin concentrations before treatment were significantly reduced, while they were normalised after treatment. After 5 cycles, the complete remission of Waldenstrms disease was reached according to biochemical parameters, and normalisation of the serum myoglobin and creatine kinase levels was achieved. PMID:26465282

  4. Isolation of 1E4 IgM Anti-Fasciola hepatica Rediae Monoclonal Antibody from Ascites: Comparison of Two Purification Protocols.

    PubMed

    Alba, Annia; Marcet, Ricardo; Otero, Oscar; Hernández, Hilda M; Figueredo, Mabel; Sarracent, Jorge

    2016-02-01

    Purification of immunoglobulin M (IgM) antibodies could be challenging, and is often characterized by the optimization of the purification protocol to best suit the particular features of the molecule. Here, two different schemes were compared to purify, from ascites, the 1E4 IgM monoclonal antibody (mAb) previously raised against the stage of redia of the trematode Fasciola hepatica. This immunoglobulin is used as capture antibody in an immunoenzymatic assay to detect parasite ongoing infection in its intermediate hosts. The first purification protocol of the 1E4 mAb involved two chromatographic steps: an affinity chromatography on a Concanavalin A matrix followed by size exclusion chromatography. An immunoaffinity chromatography was selected as the second protocol for one-step purification of the antibody using the crude extract of adult parasites coupled to a commercial matrix. Immunoreactivity of the fractions during purification schemes was assessed by indirect immunoenzymatic assays against the crude extract of F. hepatica rediae, while purity was estimated by protein electrophoresis. Losses on the recovery of the antibody isolated by the first purification protocol occurred due to protein precipitation during the concentration of the sample and to low resolution of the size exclusion molecular chromatography step regarding this particular immunoglobulin. The immunoaffinity chromatography using F. hepatica antigens as ligands proved to be the most suitable protocol yielding a pure and immunoreactive antibody. The purification protocols used are discussed regarding efficiency and difficulties. PMID:26828226

  5. Immunohistochemical detection of IgM and IgG in lung tissue of dogs with leptospiral pulmonary haemorrhage syndrome (LPHS).

    PubMed

    Schuller, Simone; Callanan, John J; Worrall, Sheila; Francey, Thierry; Schweighauser, Ariane; Kohn, Barbara; Klopfleisch, Robert; Posthaus, Horst; Nally, Jarlath E

    2015-06-01

    Leptospiral pulmonary haemorrhage syndrome (LPHS) is a severe form of leptospirosis. Pathogenic mechanisms are poorly understood. Lung tissues from 26 dogs with LPHS, 5 dogs with pulmonary haemorrhage due to other causes and 6 healthy lungs were labelled for IgG (n=26), IgM (n=25) and leptospiral antigens (n=26). Three general staining patterns for IgG/IgM were observed in lungs of dogs with LPHS with most tissues showing more than one staining pattern: (1) alveolar septal wall staining, (2) staining favouring alveolar surfaces and (3) staining of intra-alveolar fluid. Healthy control lung showed no staining, whereas haemorrhagic lung from dogs not infected with Leptospira showed staining of intra-alveolar fluid and occasionally alveolar septa. Leptospiral antigens were not detected. We conclude that deposition of IgG/IgM is demonstrable in the majority of canine lungs with naturally occurring LPHS, similar to what has been described in other species. Our findings suggest involvement of the host humoral immunity in the pathogenesis of LPHS and provide further evidence to support the dog as a natural disease model for human LPHS. PMID:25963899

  6. The IgM CH2 domain as covalently linked homodimerization module for the generation of fusion proteins with dual specificity.

    PubMed

    Seifert, Oliver; Plappert, Aline; Heidel, Nadine; Fellermeier, Sina; Messerschmidt, Sylvia K E; Richter, Fabian; Kontermann, Roland E

    2012-10-01

    Dimeric assembly of antibody fragments and other therapeutic molecules can result in increased binding and improved bioactivity. Here, we investigated the use of the IgM heavy chain domain 2 (MHD2) as covalently linked homodimerization module. Fusion of single-chain fragment variable (scFv) molecules directed against epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 to the N- and/or C-terminus of the MHD2, respectively, resulted in molecules with single or dual specificity for tumor cells. Bispecific tetravalent molecules were further generated by fusing a bispecific single-chain diabody directed against EGFR and epithelial cell adhesion molecule to the N-terminus of the MHD2. By combining an anti-EGFR scFv with a single-chain derivative of tumor necrosis factor, a tetravalent bifunctional fusion protein was produced. This fusion protein exhibited improved TNF activity, also mimicking the membrane-bound form of TNF, as shown by the activation of TNFR2-mediated cell killing. Furthermore, the scFv moiety allowed for an antigen-dependent delivery of TNF to EGFR-positive cells and an improved stimulatory TNF action on these cells. Thus, we established the MHD2 as a versatile module for the generation of bispecific and bifunctional fusion proteins. PMID:22988132

  7. Dengue virus infection induces broadly cross-reactive human IgM antibodies that recognize intact virions in humanized BLT-NSG mice

    PubMed Central

    Jaiswal, Smita; Smith, Kenneth; Ramirez, Alejandro; Woda, Marcia; Pazoles, Pamela; Shultz, Leonard D; Greiner, Dale L; Brehm, Michael A; Mathew, Anuja

    2015-01-01

    The development of small animal models that elicit human immune responses to dengue virus (DENV) is important since prior immunity is a major risk factor for developing severe dengue disease. This study evaluated anti-DENV human antibody (hAb) responses generated from immortalized B cells after DENV-2 infection in NOD-scid IL2rγnull mice that were co-transplanted with human fetal thymus and liver tissues (BLT-NSG mice). DENV-specific human antibodies predominantly of the IgM isotype were isolated during acute infection and in convalescence. We found that while a few hAbs recognized the envelope protein produced as a soluble recombinant, a number of hAbs only recognized epitopes on intact virions. The majority of the hAbs isolated during acute infection and in immune mice were serotype-cross-reactive and poorly neutralizing. Viral titers in immune BLT-NSG mice were significantly decreased after challenge with a clinical strain of dengue. DENV-specific hAbs generated in BLT-NSG mice share some of the characteristics of Abs isolated in humans with natural infection. Humanized BLT-NSG mice provide an attractive preclinical platform to assess the immunogenicity of candidate dengue vaccines. PMID:25125497

  8. Saliva IgM and IgA are a sensitive indicator of the humoral immune response to Escherichia coli O157 lipopolysaccharide in children with enteropathic hemolytic uremic syndrome.

    PubMed

    Ludwig, Kerstin; Grabhorn, Enke; Bitzan, Martin; Bobrowski, Christoph; Kemper, Markus J; Sobottka, Ingo; Laufs, Rainer; Karch, Helge; Mller-Wiefel, Dirk E

    2002-08-01

    Saliva antibodies to Escherichia coli O157 were investigated as markers of the immune response in children with enteropathic hemolytic uremic syndrome (HUS). Paired serum and saliva samples were collected from 22 children with HUS during acute disease and convalescence and were tested for E. coli O157 lipopolysaccharide (LPS)-specific IgM and IgA antibodies by ELISA. Serum and saliva samples from 44 age-matched controls were used to establish the cut-off values. Elevated levels of IgM and/or IgA antibodies to O157 LPS were detected in saliva of 13/13 HUS patients with Shiga toxin-producing E. coli (STEC) O157 in stool culture and from 4 of 5 HUS patients in whom STEC were not detected. These results closely mirrored the results obtained with paired serum samples. In contrast, saliva and serum samples from four children with STEC isolates belonging to O-groups O26, O145 (n = 2), and O165 lacked detectable O157 LPS-specific antibodies. The specificity of the ELISA was confirmed by western blotting. In STEC O157 culture-confirmed cases, the sensitivity of the ELISA was 92% for saliva IgM and IgA, based on the first available sample, and 100% and 92%, respectively, when subsequent samples were included. The specificity was 98% for IgM and 100% for IgA. Children with E. coli O157 HUS demonstrate a brisk, easily detectable immune response as reflected by the presence of specific antibodies in their saliva. Saliva-based immunoassays offer a reliable, noninvasive method for the diagnosis of E. coli O157 infection in patients with enteropathic HUS. PMID:12149511

  9. Multiplex assay (Mikrogen recomBead) for detection of serum IgG and IgM antibodies to 13 recombinant antigens of Borrelia burgdorferi sensu lato in patients with neuroborreliosis: the more the better?

    PubMed

    Dessau, Ram B; Mller, Jens K; Kolmos, Birte; Henningsson, Anna J

    2015-03-01

    A multiplex-bead-based assay for the detection of serum antibodies to Borrelia burgdorferi sensu lato was evaluated. The assay contained 13 different antigens in both the IgG and the IgM assay; thus, a total of 26 measurement results were available from each sample. A total of 49 Danish patients with Lyme neuroborreliosis (LNB), 218 Danish blood donor controls, a set of 61 Swedish patients with LNB and 139 Swedish non-LNB patients investigated for suspected LNB were used. There are four parts developed in this study: a characterization of the sero-epidemiological antibody-response pattern, the construction of a diagnostic score, evaluation of the scoring method using an independent dataset and an assessment of the analytical quality of the multiplex assay. The VlsE IgG had the highest diagnostic value with an AUC (area under the curve) of 96% on the receiver operating characteristic curve. The OspC IgM had AUCs just above 80%. All the other antigens had both low quantitative reactivity and lower contrast in the patients with LNB compared to controls. The diagnostic value of the assay may be improved by using a logistic model giving a sensitivity of 90 and 79% for the specificities at 92 and 98%, respectively. Overall, the patients with LNB had serum reactivity in IgG VlsE, but modest antibody reactivity in the remaining 12 IgG and 13 IgM antibody measurements. Using a logistic regression model with five IgG and two IgM antigens, the sensitivity and specificity of the assay was improved; but the IgG VlsE component alone contributed most of the diagnostic contrast. PMID:25587083

  10. Skin Injuries Reduce Survival and Modulate Corticosterone, C-Reactive Protein, Complement Component 3, IgM, and Prostaglandin E2 after Whole-Body Reactor-Produced Mixed Field (n + γ-Photons) Irradiation

    PubMed Central

    Kiang, Juliann G.; Ledney, G. David

    2013-01-01

    Skin injuries such as wounds or burns following whole-body γ-irradiation (radiation combined injury (RCI)) increase mortality more than whole-body γ-irradiation alone. Wound-induced decreases in survival after irradiation are triggered by sustained activation of inducible nitric oxide synthase pathways, persistent alteration of cytokine homeostasis, and increased susceptibility to systemic bacterial infection. Among these factors, radiation-induced increases in interleukin-6 (IL-6) concentrations in serum were amplified by skin wound trauma. Herein, the IL-6-induced stress proteins including C-reactive protein (CRP), complement 3 (C3), immunoglobulin M (IgM), and prostaglandin E2 (PGE2) were evaluated after skin injuries given following a mixed radiation environment that might be found after a nuclear incident. In this report, mice received 3 Gy of reactor-produced mixed field (n + γ-photons) radiations at 0.38 Gy/min followed by nonlethal skin wounding or burning. Both wounds and burns reduced survival and increased CRP, C3, and PGE2 in serum after radiation. Decreased IgM production along with an early rise in corticosterone followed by a subsequent decrease was noted for each RCI situation. These results suggest that RCI-induced alterations of corticosterone, CRP, C3, IgM, and PGE2 cause homeostatic imbalance and may contribute to reduced survival. Agents inhibiting these responses may prove to be therapeutic for RCI and improve related survival. PMID:24175013

  11. Preparation and evaluation of a recombinant Rift Valley fever virus N protein for the detection of IgG and IgM antibodies in humans and animals by indirect ELISA.

    PubMed

    Jansen van Vuren, Petrus; Potgieter, Abraham C; Paweska, Janusz T; van Dijk, Alberdina A

    2007-03-01

    This paper describes the cloning, sequencing and bacterial expression of the N protein of the Rift Valley fever virus (RVFV) ZIM688/78 isolate and its evaluation in indirect ELISAs (I-ELISA) for the detection of IgM and IgG antibodies in human and sheep sera. Sera used for the evaluation were from 106 laboratory workers immunised with an inactivated RVF vaccine, 16 RVF patients, 168 serial bleeds from 8 sheep experimentally infected with wild type RVFV and 210 serial bleeds from 10 sheep vaccinated with the live attenuated Smithburn RVFV strain. All human and animal sera that tested positive in the virus neutralisation test were also positive in the IgG I-ELISA. There was a high correlation (R2=0.8571) between virus neutralising titres and IgG I-ELISA readings in human vaccinees. In experimentally infected sheep IgG antibodies were detected from day 4 to 5 post-infection onwards and IgM antibodies from day 3 to 4. The IgG I-ELISA was more sensitive than virus neutralisation and haemagglutination-inhibition tests in detecting the early immune response in experimentally infected sheep. The I-ELISAs demonstrated that the IgG and IgM response to the Smithburn vaccine strain was slower and the levels of antibodies induced markedly lower than to wild type RVFV infection. PMID:17174410

  12. Clinical virology of Ebola hemorrhagic fever (EHF): virus, virus antigen, and IgG and IgM antibody findings among EHF patients in Kikwit, Democratic Republic of the Congo, 1995.

    PubMed

    Ksiazek, T G; Rollin, P E; Williams, A J; Bressler, D S; Martin, M L; Swanepoel, R; Burt, F J; Leman, P A; Khan, A S; Rowe, A K; Mukunu, R; Sanchez, A; Peters, C J

    1999-02-01

    Ebola hemorrhagic fever (EHF) patients treated at Kikwit General Hospital during the 1995 outbreak were tested for viral antigen, IgG and IgM antibody, and infectious virus. Viral antigen could be detected in virtually all patients during the acute phase of illness, while antibody was not always detectable before death. Virus was also isolated from patients during the course of their febrile illness, but attempts to quantify virus in Vero E6 cells by standard plaque assay were often unsuccessful. IgG and IgM antibody appeared at approximately the same time after disease onset (8-10 days), but IgM persisted for a much shorter period among the surviving convalescent patients. IgG antibody was detectable in surviving patients through about 2 years after onset, the latest time that samples were obtained. Detection of Ebola virus antigens or virus isolation appears to be the most reliable means of diagnosis for patients with suspected acute EHF, since patients with this often-fatal disease (80% mortality) may not develop detectable antibodies before death. PMID:9988182

  13. Toxicological Effects of Nickel Chloride on IgA+ B Cells and sIgA, IgA, IgG, IgM in the Intestinal Mucosal Immunity in Broilers

    PubMed Central

    Wu, Bangyuan; Cui, Hengmin; Peng, Xi; Fang, Jing; Zuo, Zhicai; Deng, Junliang; Huang, Jianying

    2014-01-01

    The objective of this study was to investigate the toxicological effects of dietary NiCl2 on IgA+ B cells and the immunoglobulins including sIgA, IgA, IgG and IgM in the small intestine and cecal tonsil of broilers by the methods of immunohistochemistry and enzyme-linked immunosorbent assay (ELISA). Two hundred and forty one-day-old avian broilers were randomly divided into four groups and fed on a control diet and three experimental diets supplemented with 300, 600, and 900 mg/kg NiCl2 for 42 days. Compared with the control group, the IgA+ B cell number and the sIgA, IgA, IgG, and IgM contents in the NiCl2-treated groups were significantly decreased (p < 0.05 or p < 0.01). It was concluded that dietary NiCl2 in the excess of 300 mg/kg had negative effects on the IgA+ B cell number and the abovementioned immunoglobulin contents in the small intestine and the cecal tonsil. NiCl2-reduced sIgA, IgA, IgG and IgM contents is due to decrease in the population and/or the activation of B cell. The results suggest that NiCl2 at high levels has intestinal mucosal humoral immunotoxicity in animals. PMID:25116637

  14. Data mining of supersecondary structure homology between light chains of immunogloblins and MHC molecules: absence of the common conformational fragment in the human IgM rheumatoid factor.

    PubMed

    Izumi, Hiroshi; Wakisaka, Akihiro; Nafie, Laurence A; Dukor, Rina K

    2013-03-25

    It is shown that fuzzy search and data mining techniques of supersecondary structure homology for subunits of proteins using conformational code patterns of α-helix-type (3β5α4β) and β-sheet-type (6α4β4β) fragments can be used to extract correlations between fragments of MHC class I molecules and the light chain of immunoglobulins. The new method of conformational pattern analysis with fuzzy search of structural code homology reflects well the shape of main chain rather than secondary structure in comparison with the DSSP method. Further, the data mining technique using the combination of h- and s-fragment patterns can quantify the supersecondary structure homology between any subunits of proteins with different amino acid sequences. Characteristic fragment patterns (string "shhshss"), which were sandwiched between two identical amino acid sequences His and Pro, were found in light chains of various types of immunogloblins, α-chain and β-2 microglobulin of MHC class I and α-chain and β-chain of MHC class II, but not in heavy chains of Fab immunoglobulin fragments and T cell receptors (TCR). Leukocyte immunoglobulin-like receptors (LILR) are related by the conformational fragment (string "shhshss") to β-2 microglobulins as a type of pair forms (string "sohsss"). Further, human IgM rheumatoid factor, one of the immunogloblins, did not strongly exhibit the conformational fragment pattern. Nonclassic MHC class I molecules CD1D, MIC-A, and MIC-B, which have functions to activate NKT, NK, and T cells, did not also clearly show the patterns. These code-driven mining techniques can be utilized as a metadata-generating tool for systems biology to elucidate the biological function of such conformational fragments of MHC I and II molecules, which come in contact with various signal ligands on the surface of T cells and natural killer cells. PMID:23394723

  15. Enhancement by ascorbic acid 2-glucoside or repeated additions of ascorbate of mitogen-induced IgM and IgG productions by human peripheral blood lymphocytes.

    PubMed

    Tanaka, M; Muto, N; Gohda, E; Yamamoto, I

    1994-12-01

    In this study, the effect of ascorbic acid 2-glucoside (AA-2G), a stable derivative of ascorbic acid (AsA), or repeated additions of ascorbate on antibody productions by human peripheral blood lymphocytes (PBLs) was examined, and the physiological function of AsA was evaluated. When human PBLs were stimulated with Staphylococcus aureus Cowan I or pokeweed mitogen, AA-2G remarkably increased the numbers of IgM- and IgG-secreting cells which were detected by enzyme-linked immunospot assay. Although a single addition of ascorbate was without effect, the effect of AA-2G was remarkably inhibited by the addition of castanospermine, an alpha-glucosidase inhibitor; and moreover, repeated additions of AsA to the culture medium during the culture period enhanced the response to the same level as did a single addition of AA-2G. These results indicate that AsA has the ability to stimulate the immunoglobulin productions by AA-2G. The phytohemagglutinin-induced proliferative response of PBLs was also stimulated by AA-2G. The intracellular AsA content in PBLs cultured with AA-2G was maintained at relatively high levels during the culture period, whereas the content with a single dose of AsA reached nearly zero by the end of the experiment. These in vitro findings suggest that AA-2G and AsA function as potent immunostimulators of antibody production in humans and that the intracellular AsA content is a key parameter for establishing the immune response of PBLs. PMID:7723222

  16. Increased chronic lymphocytic leukemia proliferation upon IgM stimulation is sustained by the upregulation of miR-132 and miR-212.

    PubMed

    Tavolaro, Simona; Colombo, Teresa; Chiaretti, Sabina; Peragine, Nadia; Fulci, Valerio; Ricciardi, Maria R; Messina, Monica; Bonina, Silvia; Brugnoletti, Fulvia; Marinelli, Marilisa; Di Maio, Valeria; Mauro, Francesca R; Del Giudice, Ilaria; Macino, Giuseppe; Fo, Robin; Guarini, Anna

    2015-04-01

    To assess the involvement of microRNAs (miRNAs) in B-cell receptor (BCR) stimulation, we first evaluated miRNA profiling following IgM cross-linking in chronic lymphocytic leukemia (CLL) cells and in normal B lymphocytes. Second, we combined miRNA and gene expression data to identify putative miRNA functional networks. miRNA profiling showed distinctive patterns of regulation after stimulation in leukemic versus normal B lymphocytes and identified a differential responsiveness to BCR engagement in CLL subgroups according to the immunoglobulin heavy chain variable region mutational status and clinical outcome. The most significantly modulated miRNAs in stimulated CLL are miR-132 and miR-212. Notably, these miRNAs appeared regulated in progressive but not in stable CLL. Accordingly, gene profiling showed a significant transcriptional response to stimulation exclusively in progressive CLL. Based on these findings, we combined miRNA and gene expression data to investigate miR-132 and miR-212 candidate interactions in this CLL subgroup. Correlation analysis pointed to a link between these miRNAs and RB/E2F and TP53 cascades with proproliferative effects, as corroborated by functional analyses. Finally, basal levels of miR-132 and miR-212 were measured in an independent cohort of 20 unstimulated CLL cases and both showed lower expression in progressive compared to stable patients, suggesting an association between the expression of these molecules and disease prognosis. Overall, our results support a model involving miR-132 and miR-212 upregulation in sustaining disease progression in CLL. These miRNAs may therefore provide new valuable strategies for therapeutic intervention. PMID:25645730

  17. Diagnostic accuracy and comparison of two assays for Borrelia-specific IgG and IgM antibodies: proposals for statistical evaluation methods, cut-off values and standardization.

    PubMed

    Dessau, Ram Benny

    2013-12-01

    Two assays (Liaison, Diasorin; IDEIA, Oxoid) for detection of Borrelia-specific antibodies were compared. A case-control design using patients with neuroborreliosis (n?=?48), laboratory defined by a positive Borrelia-specific antibody index in the spinal fluid, was available and was intended to represent the serological response of disseminated early Lyme borreliosis in general. Serum samples were obtained from 216 Danish blood donors as controls. By comparing sensitivity and specificity using pre-specified cut-off values, significant differences were found. However, using receiver operating characteristic (ROC) curves to optimize and standardize test interpretation, it was shown that testing with both IDEIA IgG and IgM was comparable to testing with Liaison IgG alone by comparing the area under the curve of the diagnostically relevant 25?% partial ROC curve (P?=?0.1). When using the Liaison OspC/VlsE IgM assay, the specificity was decreased without a gain in sensitivity. This study proposes standardizing of reporting by using a control population as the reference and choosing decision thresholds guided by the risk of false-positive results at 2 and 8?%. The sensitivities for IDEIA (IgG and IgM combined) were 85 and 95?% and for the Liaison (VlsE IgG) method were 67 and 96?%, respectively. Methods for test evaluation, test interpretation and statistical testing are presented and discussed. In conclusion, Liaison VlsE IgG alone and IDEIA IgG/IgM combined showed a high and comparable discriminatory ability to distinguish serum samples from patients with neuroborreliosis from blood donor controls. However, cut-off values should be adjusted for a proper comparison. PMID:24072766

  18. Evaluation of 12 commercial tests and the complement fixation test for Mycoplasma pneumoniae-specific immunoglobulin G (IgG) and IgM antibodies, with PCR used as the "gold standard".

    PubMed

    Beersma, Matthias F C; Dirven, Kristien; van Dam, Alje P; Templeton, Kate E; Claas, Eric C J; Goossens, Herman

    2005-05-01

    Serology and nucleic acid amplification are the main diagnostic tools for the diagnosis of Mycoplasma pneumoniae infection. Since no reference standard is generally accepted, serologic assays for M. pneumoniae have not been evaluated on a broad scale. In this study, 12 commercially available serologic assays (for immunoglobulin G [IgG] and IgM) and the complement fixation test (CFT) were evaluated by using M. pneumoniae DNA detection by real-time PCR as the "gold standard." The assays tested were Platelia EIA (Bio-Rad), SeroMP EIA (Savyon), Serion classic EIA (Virion/Serion), Biotest EIA (Biotest), Ridascreen EIA (r-Biopharm), AniLabsystems EIA (Labsystems), Novum EIA (Novum Diagnostica), Diagnosys EIA (MP products), Genzyme/Virotech EIA, ImmunoWell EIA (Genbio), ImmunoCard EIA (Meridian), and SerodiaMycoII microparticle agglutination (Fujirebio). Serum samples (n = 46) from 27 PCR-positive patients with a known first day of disease and sera (n = 33) from PCR-negative controls were obtained from prospective studies of acute lower respiratory tract infections. Additionally, control sera (n = 63) from patients with acute viral or bacterial respiratory infections other than those caused by M. pneumoniae were tested. The results showed low specificities for both the Novum and the ImmunoCard IgM assays. The IgM assays with the best performances in terms of sensitivity and specificity were AniLabsystems (77% and 92%, respectively), SeroMP (71% and 88%, respectively), and CFT (65% and 97%, respectively). Good receiver operating characteristic areas under the curve were found for CFT (0.94), the Platelia assay (0.87), and the AniLabsystems assay (0.85). We conclude that there are few commercial serologic assays for the detection of M. pneumoniae infections with appropriate performances in terms of sensitivity and specificity and that PCR has become increasingly important for the diagnosis of M. pneumoniae infections in defined groups of patients. PMID:15872256

  19. Immunogenic cells in the regional lymph nodes after painting with the contact sensitizers picryl chloride and oxazolone: evidence for the presence of IgM antibody on their surface

    PubMed Central

    Asherson, G. L.; Colizzi, V.; Watkins, Madeleine C.

    1983-01-01

    The lymph node cells of mice painted with contact sensitizing agents immunize recipient mice when injected into their footpads. In practice 2 106 nylon wool purified T cells are used from mice painted with picryl chloride or oxazolone (4-ethoxymethylene-2-phenyloxazolone). The ability of cells taken 4 days after painting to immunize other mice was abolished by treatment with rabbit complement but cells taken at 1 day were unaffected. This effect of rabbit complement was due to IgM anti-hapten antibody on the surface of antigen-presenting cells. The antibody could be eluted from the cells with appropriate picryl or oxazolone-?-aminocaproic acid. It adhered to insolubilized anti-IgM and behaved like IgM on gel filtration. To confirm the role of this antibody, mice were rendered unresponsive with picrylated pneumococcal polysaccharide type III before being painted. This abolishes antibody production but leaves contact sensitivity intact. The lymph node cells of animals treated in this way were unaffected by rabbit complement and this suggested that antibody was required for this phenomenon. Moreover although lymph nodes normally lose the ability to immunize at day 6 after painting, the lymph node cells of unresponsive mice, which fail to make antibody immunize other mice up to day 8 after painting. This effect of unresponsiveness is reversed by the injection of serum taken 8 days after painting. It was concluded that IgM antibody which appears on the surface of lymph nodes 4 days after painting depresses their ability to immunize other mice. PMID:6826205

  20. The polymorphism p.G219R of CD40L does not cause immunological alterations in vivo: conclusions from a X-linked hyper IgM syndrome kindred.

    PubMed

    Martinez-Martinez, Laura; Gonzalez-Santesteban, Cecilia; Badell, Isabel; de la Calle-Martin, Oscar

    2012-10-01

    Hyper-IgM syndromes (HIGM) are characterized by low levels of IgG, IgA and IgE and normal to high levels of IgM. Patients with these syndromes present recurrent infections due to an impaired immunoglobulin maturation. The most prevalent form of HIGM, X-linked hyper IgM syndrome (XHIM), is caused by mutations in the gene encoding the CD40 ligand (CD40LG). We present two siblings with XHIM caused by a large CD40LG deletion affecting more than half of the gene, and extended from the end of intron 3 to far upstream of the promoter regions. Genetic analysis in the maternal family discovered the CD40L(G219R) polymorphism in several members. Segregation of this polymorphism in the kindred indicated that the deletion of CD40LG was a de novo mutation in the mother. Although half of her CD4+ T cells did not express CD40L and the other half expressed the CD40L(G219R) variant, the mother was healthy. This suggests that this polymorphism is not pathogenic by itself although it has been recently related to X-linked lymphoproliferative syndrome. PMID:22750225

  1. A Prospective Assessment of the Accuracy of Commercial IgM ELISAs in Diagnosis of Japanese Encephalitis Virus Infections in Patients with Suspected Central Nervous System Infections in Laos

    PubMed Central

    Moore, Catrin E.; Blacksell, Stuart D.; Taojaikong, Thaksinaporn; Jarman, Richard G.; Gibbons, Robert V.; Lee, Sue J.; Chansamouth, Vilada; Thongpaseuth, Soulignasack; Mayxay, Mayfong; Newton, Paul N.

    2012-01-01

    Japanese encephalitis virus (JEV) is a major cause of encephalitis in Asia. We estimated the diagnostic accuracy of two anti-JEV immunoglobulin M (IgM) enzyme-linked immunosorbent assays (ELISAs) (Panbio and XCyton JEVCheX) compared with a reference standard (AFRIMS JEV MAC ELISA) in a prospective study of the causes of central nervous system infections in Laos. Cerebrospinal fluid (CSF; 515 patients) and serum samples (182 patients) from those admitted to Mahosot Hospital, Vientiane, were tested. The CSF from 14.5% of acute encephalitis syndrome (AES) patients and 10.1% from those with AES and meningitis were positive for anti-JEV IgM in the reference ELISA. The sensitivities for CSF were 65.4% (95% confidence interval [CI] = 5178) (Xcyton), 69.2% (95% CI = 5581) (Panbio), however 96.2% (95% CI = 87100) with Panbio Ravi criteria. Specificities were 89100%. For admission sera from AES patients, sensitivities and specificities of the Panbio ELISA were 85.7% (95% CI = 42100%) and 92.9% (95% CI = 8398%), respectively. PMID:22764310

  2. Coxsackievirus B1-based antibody-capture enzyme-linked immunosorbent assay for detection of immunoglobulin G (IgG), IgM, and IgA with broad specificity for enteroviruses.

    PubMed Central

    Swanink, C M; Veenstra, L; Poort, Y A; Kaan, J A; Galama, J M

    1993-01-01

    An antibody-capture enzyme-linked immunosorbent assay (ELISA) with coxsackievirus B1 as the antigen was evaluated for detection of immunoglobulin G (IgG), IgM, and IgA antibodies and showed broad specificity for enteroviruses. In total, 116 serum or cerebrospinal fluid samples from 62 patients were tested by ELISA and the complement fixation test (CFT). Additionally, 15 serum samples that contained poliovirus-specific IgM antibody were tested. Serum samples from 200 healthy blood donors were used for standardization of the assays. The sensitivity of the ELISA varied with time of serum sampling, with a relatively low sensitivity when serum was collected within 3 days after the onset of symptoms (23%; 5 of 22) but good sensitivity when serum was collected later (83%; 20 of 24). The sensitivity was better than that of the CFT. The ELISAs were broadly reactive as concluded from typing of virus isolates that were simultaneously obtained. The assay did, furthermore, detect antibody against poliovirus type 3. Sera that contained rheumatoid factor, antinuclear antibody, or cardiolipin antibody (by the Venereal Disease Research Laboratory test) did not react in this ELISA. Nonspecific reactivity did occur, however, in cases of infectious mononucleosis and in Mycoplasma pneumoniae infection. The enterovirus-specific ELISA is found to be simple to perform, more sensitive than the CFT, and far less laborious than the neutralization test. PMID:8308117

  3. Characterization and antivirus activities of a novel bovine IFN-omega24.

    PubMed

    Luo, Xiuxin; Guo, Yongli; Bao, Jun; Liu, Ying; An, Dong; Ma, Bo; Gao, Mingchun; Wang, Junwei

    2015-08-01

    A novel bovine interferon-ω (BoIFN-ω) gene, which encodes a protein of 195 amino acids with a 23-amino acid signal peptide, was amplified from bovine liver genomic DNA through PCR and named BoIFN-ω24 according to its position in the bovine genome. In this study, the recombinant protein was expressed in Escherichia coli and antiviral or antiproliferation activity was determined in vitro. Results showed that BoIFN-ω24 exhibits high antiviral activity, which can be abrogated using PAb against BoIFN-ω24, and inhibits cell proliferation. BoIFN-ω24 also presents high sensitivity to trypsin and stability at pH 2.0 or 65°C, which are typical characteristics of type I IFN. This study revealed that BoIFN-ω24 is a potential novel effective therapeutic agent and provided a basis for further research on the BoIFN-ω multigene family. PMID:25951414

  4. Comparison of the Specificities of IgG, IgG-Subclass, IgA and IgM Reactivities in African and European HIV-Infected Individuals with an HIV-1 Clade C Proteome-Based Array

    PubMed Central

    Gallerano, Daniela; Ndlovu, Portia; Makupe, Ian; Focke-Tejkl, Margarete; Fauland, Kerstin; Wollmann, Eva; Puchhammer-Stckl, Elisabeth; Keller, Walter; Sibanda, Elopy; Valenta, Rudolf

    2015-01-01

    A comprehensive set of recombinant proteins and peptides of the proteome of HIV-1 clade C was prepared and purified and used to measure IgG, IgG-subclass, IgA and IgM responses in HIV-infected patients from Sub-Saharan Africa, where clade C is predominant. As a comparison group, HIV-infected patients from Europe were tested. African and European patients showed an almost identical antibody reactivity profile in terms of epitope specificity and involvement of IgG, IgG subclass, IgA and IgM responses. A V3-peptide of gp120 was identified as major epitope recognized by IgG1>IgG2 = IgG4>IgG3, IgA>IgM antibodies and a C-terminal peptide represented another major peptide epitope for the four IgG subclasses. By contrast, gp41-derived-peptides were mainly recognized by IgG1 but not by the other IgG subclasses, IgA or IgM. Among the non-surface proteins, protease, reverse transcriptase+RNAseH, integrase, as well as the capsid and matrix proteins were the most frequently and strongly recognized antigens which showed broad IgG subclass and IgA reactivity. Specificities and magnitudes of antibody responses in African patients were stable during disease and antiretroviral treatment, and persisted despite severe T cell loss. Using a comprehensive panel of gp120, gp41 peptides and recombinant non-surface proteins of HIV-1 clade C we found an almost identical antibody recognition profile in African and European patients regarding epitopes and involved IgG-sublass, IgA- and IgM-responses. Immune recognition of gp120 peptides and non-surface proteins involved all four IgG subclasses and was indicative of a mixed Th1/Th2 immune response. The HIV-1 clade C proteome-based test allowed diagnosis and monitoring of antibody responses in the course of HIV-infections and assessment of isotype and subclass responses. PMID:25658330

  5. Specific IgM, IgG and IgG1 directed against Toxoplasma gondii detected by flow cytometry and their potential as serologic tools to support clinical indirect fundoscopic presumed diagnosis of ocular disease.

    PubMed

    Martins, Livia Mattos; Rangel, Alba Lucinia Peixoto; Peixe, Ricardo Guerra; Silva-dos-Santos, Priscila Pinto; Lemos, Elenice Moreira; Martins-Filho, Olindo Assis; Bahia-Oliveira, Lilian Maria Garcia

    2015-02-01

    In the present study we evaluated the anti-Toxoplasma gondii immunoglobulin profiles of a group of 118 individuals living in an endemic area. The aim of the study was to select biomarkers to support the ophthalmological diagnosis of retinal/retinochoroidal scars presumably caused by T. gondii infection. Overall anti-T. gondii reactivity of the IgM, IgG, IgA, IgE and IgG subclasses was investigated by flow cytometry-based anti-fixed tachyzoite antibodies (FC-AFTA) in four groups of subjects, referred to as: i) TOXO(L)--seropositive patients with retinal/retinochoroidal scars presumably caused by T. gondii infection; these patients were further subdivided according to morphological aspects of their ocular scar lesions as A, B or C; ii) TOXO(NL)--seropositive patients without ocular scar lesions; iii) NEG(L)--T. gondii seronegative patients presenting retinal lesions; and iv) NEG(NL)--T. gondii seronegative without retinal lesions (negative controls). Our data demonstrated that anti-T. gondii IgG profiles were able to discriminate the mean reactivity of TOXO(L) from all other clinical groups. Analysis of anti-T. gondii immunoglobulin profiles revealed that IgM and IgG were good biomarkers capable of discriminating between individual reactivity in patients with retinal/retinochoroidal scars presumably caused by T. gondii infection [TOXO(L)] from those caused by other clinical conditions. Furthermore, anti-T. gondii IgG1 reactivity was able to discriminate TOXO(L) from all other clinical groups. In conclusion, the pre-selected IgM, IgG and IgG1 anti-T. gondii antibody subclasses were able to segregate both TOXO(L) and the other subgroups, including the scar lesion group types (A, B, C), from other clinical conditions. These results suggest the applicability of this technique in the clinical laboratory to detect putative biomarker for diagnosis of ocular lesions in T. gondii-infected patients. Studies in other areas implementing the methods described in the present study would be of value and enable evaluation of a system for classification of presumed ocular toxoplasmosis scar lesions. This classification would make comparative studies on ocular toxoplasmosis conducted in different regions around the world possible. PMID:25527345

  6. Characterization of Human Class-Switched Polymeric (Immunoglobulin M [IgM] and IgA) Anti-Human Immunodeficiency Virus Type 1 Antibodies 2F5 and 2G12

    PubMed Central

    Wolbank, Susanne; Kunert, Renate; Stiegler, Gabriela; Katinger, Hermann

    2003-01-01

    We have previously generated human monoclonal anti-human immunodeficiency virus type 1 (anti-HIV-1) antibodies 2F5IgG and 2G12IgG with an exceptional cross-clade neutralizing potential. 2F5IgG and 2G12IgG passively administrated to macaques were able to confer complete protection from both intravenous and mucosal challenge with pathogenic HIV-simian immunodeficiency virus chimeric strains and have shown beneficial effects in a phase-1 clinical trial. We now class-switched 2F5 and 2G12 to the immunoglobulin M (IgM) or IgA isotype, to enforce features like avidity, complement activation, or the potential to neutralize mucosal transmission. For this purpose we expressed functional polymeric 2F5 and 2G12 antibodies in CHO cells and evaluated their anti-HIV-1 activity in vitro. The class switch had a strong impact on the protective potential of 2F5 and 2G12. 2G12IgM inhibited HIV-1 infection of peripheral blood mononuclear cell cultures up to 28-fold-more efficiently than the corresponding IgG and neutralized all of the primary isolates tested. The 2F5 and 2G12 antibodies of all isotypes were able to interact with active human serum to inhibit viral infection. Furthermore, we demonstrated that polymeric 2F5 and 2G12 antibodies but not the corresponding IgGs could interfere with HIV-1 entry across a mucosal epithelial layer in vitro. Although polymeric 2F5 antibodies had only limited potential in the standard neutralization assay, the results from the mucosal assay suggest that 2F5 and 2G12 antibodies may have a high potential to prevent natural HIV-1 transmission in vivo. PMID:12634368

  7. CD40 Ligand Deficient C57BL/6 Mouse Is a Potential Surrogate Model of Human X-Linked Hyper IgM (X-HIGM) Syndrome for Characterizing Immune Responses against Pathogens

    PubMed Central

    Lopez-Saucedo, Catalina; Bernal-Reynaga, Rodolfo; Zayas-Jahuey, Jesus; Galindo-Gomez, Silvia; Shibayama, Mineko; Garcia-Galvez, Carlos; Estrada-Parra, Sergio; Estrada-Garcia, Teresa

    2015-01-01

    Individuals with X-HIGM syndrome fail to express functional CD40 ligand; consequently they cannot mount effective protective antibody responses against pathogenic bacteria. We evaluated, compared, and characterized the humoral immune response of wild type (WT) and C57-CD40L deficient (C57-CD40L?/?) mice infected with Citrobacter rodentium. Basal serum isotype levels were similar for IgM and IgG3 among mice, while total IgG and IgG2b concentrations were significantly lower in C57-CD40L?/? mice compared with WT. Essentially IgG1 and IgG2c levels were detectable only in WT mice. C57-CD40L?/? animals, orally inoculated with 2 109 CFU, presented several clinical manifestations since the second week of infection and eventually died. In contrast at this time point no clinical manifestations were observed among C57-CD40L?/? mice infected with 1 107 CFU. Infection was subclinical in WT mice inoculated with either bacterial dose. The serum samples from infected mice (1 107 CFU), collected at day 14 after infection, had similar C. rodentium-specific IgM titres. Although C57-CD40L?/? animals had lower IgG and IgG2b titres than WT mice, C57-CD40L?/? mice sera displayed complement-mediated bactericidal activity against C. rodentium. C. rodentium-infected C57-CD40L?/? mice are capable of producing antibodies that are protective. C57-CD40L?/? mouse is a useful surrogate model of X-HIGM syndrome for studying immune responses elicited against pathogens. PMID:26064940

  8. CD40 Ligand Deficient C57BL/6 Mouse Is a Potential Surrogate Model of Human X-Linked Hyper IgM (X-HIGM) Syndrome for Characterizing Immune Responses against Pathogens.

    PubMed

    Lopez-Saucedo, Catalina; Bernal-Reynaga, Rodolfo; Zayas-Jahuey, Jesus; Galindo-Gomez, Silvia; Shibayama, Mineko; Garcia-Galvez, Carlos; Estrada-Parra, Sergio; Estrada-Garcia, Teresa

    2015-01-01

    Individuals with X-HIGM syndrome fail to express functional CD40 ligand; consequently they cannot mount effective protective antibody responses against pathogenic bacteria. We evaluated, compared, and characterized the humoral immune response of wild type (WT) and C57-CD40L deficient (C57-CD40L(-/-)) mice infected with Citrobacter rodentium. Basal serum isotype levels were similar for IgM and IgG3 among mice, while total IgG and IgG2b concentrations were significantly lower in C57-CD40L(-/-) mice compared with WT. Essentially IgG1 and IgG2c levels were detectable only in WT mice. C57-CD40L(-/-) animals, orally inoculated with 2 10(9) CFU, presented several clinical manifestations since the second week of infection and eventually died. In contrast at this time point no clinical manifestations were observed among C57-CD40L(-/-) mice infected with 1 10(7) CFU. Infection was subclinical in WT mice inoculated with either bacterial dose. The serum samples from infected mice (1 10(7) CFU), collected at day 14 after infection, had similar C. rodentium-specific IgM titres. Although C57-CD40L(-/-) animals had lower IgG and IgG2b titres than WT mice, C57-CD40L(-/-) mice sera displayed complement-mediated bactericidal activity against C. rodentium. C. rodentium-infected C57-CD40L(-/-) mice are capable of producing antibodies that are protective. C57-CD40L(-/-) mouse is a useful surrogate model of X-HIGM syndrome for studying immune responses elicited against pathogens. PMID:26064940

  9. Decreased IgA+ B Cells Population and IgA, IgG, IgM Contents of the Cecal Tonsil Induced by Dietary High Fluorine in Broilers

    PubMed Central

    Liu, Juan; Cui, Hengmin; Peng, Xi; Fang, Jing; Zuo, Zhicai; Deng, Junliang; Wang, Hesong; Wu, Bangyuan; Deng, Yuanxin; Wang, Kangping

    2013-01-01

    Fluoride is an environmental and industrial pollutant that affects various organs in humans and animals. The cecal tonsil is an important component of the mucosal immune system and performs important and unique immune functions. In the present study, we investigated the effects of dietary high fluorine on the quantities of IgA+ B cells in the cecal tonsil by immunohistochemistry, and the immunoglobulin A (IgA), immunoglobulin G (IgG) and immunoglobulin M (IgM) contents in the cecal tonsil by ELISA. A total of 280 one-day-old avian broilers were divided into four groups and fed on a corn-soybean basal diet as control diet (fluorine 22.6 mg/kg) or the same diet supplemented with 400, 800 and 1,200 mg/kg fluorine (high fluorine groups I, II and III) in the form of sodium fluoride, respectively, throughout a 42-day experimental period. The results showed that the quantities of IgA+ B cells were lower (p < 0.05 or p < 0.01) and the IgA, IgG, and IgM contents were decreased (p < 0.05 or p < 0.01) in high fluorine groups II and III in comparison with those of control group. It was concluded that dietary fluorine, in the 8001,200 mg/kg range, could reduce the numbers of the IgA+ B cells and immunoglobulin contents in the cecal tonsil, implying the local mucosal immune function was ultimately impacted in broilers. PMID:23644827

  10. IgM, IgG, and IgA Antibody Responses to Influenza A(H1N1)pdm09 Hemagglutinin in Infected Persons during the First Wave of the 2009 Pandemic in the United States

    PubMed Central

    Lin, Seh-Ching; Carney, Paul J.; Li, Ji; Liu, Feng; Lu, Xiuhua; Liu, Merry; Stevens, James; Levine, Min; Katz, Jacqueline M.; Hancock, Kathy

    2014-01-01

    The novel influenza A(H1N1)pdm09 virus caused an influenza pandemic in 2009. IgM, IgG, and IgA antibody responses to A(H1N1)pdm09 hemagglutinin (HA) following A(H1N1)pdm09 virus infection were analyzed to understand antibody isotype responses. Age-matched control sera collected from U.S. residents in 2007 and 2008 were used to establish baseline levels of cross-reactive antibodies. IgM responses often used as indicators of primary virus infection were mainly detected in young patient groups (?5 years and 6 to 15 years old), not in older age groups, despite the genetic and antigenic differences between the HA of A(H1N1)pdm09 virus and pre-2009 seasonal H1N1 viruses. IgG and IgA responses to A(H1N1)pdm09 HA were detected in all age groups of infected persons. In persons 17 to 80 years old, paired acute- and convalescent-phase serum samples demonstrated ?4-fold increases in the IgG and IgA responses to A(H1N1)pdm09 HA in 80% and 67% of A(H1N1)pdm09 virus-infected persons, respectively. The IgG antibody response to A(H1N1)pdm09 HA was cross-reactive with HAs from H1, H3, H5, and H13 subtypes, suggesting that infections with subtypes other than A(H1N1)pdm09 might result in false positives by enzyme-linked immunosorbent assay (ELISA). Lower sensitivity compared to hemagglutination inhibition and microneutralization assays and the detection of cross-reactive antibodies against homologous and heterologous subtype are major drawbacks for the application of ELISA in influenza serologic studies. PMID:24872516

  11. A case of acute humoral rejection with various depositions of C4d, IgG, IgM, and C3c in peritubular capillaries and/or glomerular capillaries.

    PubMed

    Shimizu, Tomokazu; Tanabe, Kazunari; Tokumoto, Tadahiko; Kanemitsu, Izumi; Tsunoyama, Kuniko; Ishida, Hideki; Ishikawa, Nobuo; Toma, Hiroshi; Yamaguchi, Yutaka

    2005-01-01

    A 41-year-old Japanese male patient with end-stage renal disease received ABO compatible living related kidney transplantation from his sister on April 2003. The kidney functioned immediately after kidney transplantation. Protocol allograft biopsy at 1 yr after kidney transplantation was performed on April 2004. His serological data was not particular and he did not suffer with chronic inflammation. The allograft biopsy specimen revealed moderate accumulations of polymorphonuclear leukocytes in peritubular capillaries (PTCs), dilatation of PTCs and moderate infiltrations of polymorphonuclear and/or mononuclear cell in glomeruli (Transplant glomerulitis, moderate). Immunofluorescent study (IF) of a frozen section of the allograft biopsy specimen showed a strong, diffusely distributed endothelial-staining pattern in PTCs for C4d. The C4d was also strongly detected in a linear glomerular basement membrane (GBM) pattern. And widespread moderate C3c deposits, weak IgM, and IgG deposits were also seen in PTCs. Immunofluorescent study also showed granularly peripheral and mesangial deposits of strong IgM, C1q, and moderate IgG in glomeruli, IgA and C3c were faintly positive. The panel reactive antibody, which had been negative before transplantation, was positive for both HLA classes I and II at that time. We diagnosed as acute humoral rejection (AHR) and he was treated with course of steroid pulses and 5 d of gusperimus (DSG); and a total of three times Plasma exchange (PE) treatment was added. The level of serum creatinine, once increased to 1.7 mg/dL, decreased gradually to 1.4 mg/dL. He has a stable graft function. This is the only case of various depositions of immunoglobulins and complements in PTC and/or glomerular capillaries during AHR. PMID:15955172

  12. Effects of heat stress on peripheral T and B lymphocyte profiles and IgG and IgM serum levels in broiler chickens vaccinated for Newcastle disease virus.

    PubMed

    Honda, Bruno Takashi Bueno; Calefi, Atilio Sersun; Costola-de-Souza, Carolina; Quinteiro-Filho, Wanderley Moreno; da Silva Fonseca, Juliana Garcia; de Paula, Viviane Ferraz; Palermo-Neto, João

    2015-10-01

    Multiple factors, such as environment, nutritional status, and disease, induce stress in animals during livestock production. It has been shown that poultry exposed to stressors for prolonged periods had decreases in their performance parameters, mortality and decreased host resistance to pathogenic agents. It seems that early age stress may have long-lasting impact and could possibly modify the expression of their genetic potential on growth performance and immunity. This study aimed to discuss the effects of early-age heat stress on the blood lymphocyte phenotypes (B and T lymphocytes) and plasma immunoglobulin levels (IgM and IgG) in chickens vaccinated against paramixovirus of the Newcastle (NC) disease (LaSota strain). For this purpose, 96 male chickens (Cobb) were divided into 4 groups: 1) control (C), 2) heat-stressed (HS), 3) control vaccinated (C/V), and 4) heat-stressed and Vaccinated (HS/V). The NC vaccine was administered twice on experimental day (ED) 7 and ED14, and the heat stress (38 ± 1°C) was applied from ED2 to ED6. The data showed that HS increased the corticosterone serum levels in the HS group compared with the control groups (C and C/V groups). At ED7, increased concentrations of IgM were observed in birds in the HS and HS/V groups compared with C and C/V animals; chickens from the HS/V group presented increased IgG levels compared with those in the birds of the C group. The heat stress shifted the immune cell profile from B-lymphocyte to a T-cytotoxic and T-helper lymphocyte profile, and this immune cell pattern persisted until the end of the study period. It was concluded that heat stress immunomodulated the immune function response of the chickens to the NC disease vaccine challenge. PMID:26362974

  13. Evaluation of a colloidal gold immunochromatography assay in the detection of Treponema pallidum specific IgM antibody in syphilis serofast reaction patients: a serologic marker for the relapse and infection of syphilis.

    PubMed

    Lin, Li-Rong; Tong, Man-Li; Fu, Zuo-Gen; Dan, Bing; Zheng, Wei-Hong; Zhang, Chang-Gong; Yang, Tian-Ci; Zhang, Zhong-Ying

    2011-05-01

    Syphilis remains as a worldwide public health problem; hence, it is necessary to develop a new diagnostic approach that is easier and faster than conventional tests. A new testing method to detect Treponema pallidum IgM (TP-IgM), named colloidal gold immunochromatography assay (GICA), is presented in place of fluorescent treponemal antibody absorption (FTA-Abs). TP-IgM was detected using GICA developed on syphilis-specific recombinant proteins TPN17 and TPN47. The FTA-Abs IgM test was set as the gold standard. A GICA TP-IgM test was performed to detect syphilis in 1208 patients who received recommended therapy for syphilis for more than 1 year at the Xiamen Center of Clinical Laboratory in China from June 2005 to May 2009. One hundred blood donors were set up as control. The sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio were 98.21%, 99.04%, 93.75%, 99.73%, 102.3, and 0.018, respectively. Detection on 500 interference specimens indicated that the biological false-positive rate of the GICA test was extremely low and was free from other biological and chemical factors. The patients were divided into the following experimental groups based on the results of toluidine red unheated serum test (TRUST) and treponemal pallidum particle agglutination (TPPA): (1) the syphilis serofast reaction (SSR) group consisted of 411 cases with (+) TRUST and (+) TPPA, which exhibited no clinical manifestations of syphilis after 1 year of recommended syphilis treatment; (2) the serum cure group, which was further subdivided into group A, a group that consisted of 251 cases with (-) TRUST and (+) TPPA, and (3) group B, a group that consisted of 546 cases with (-) TRUST and (-) TPPA; and (4) the blood donor control group, which consisted of 100 healthy persons with (-) ELISA-TP and (-) TPPA. We used the FTA-Abs method and the GICA method to detect TP-IgM; the positive rate of TP-IgM in 411 SSR patients was 34.55% and 36.01%, respectively. However, in serum cure group A, the positive rate of TP-IgM was 10.36% and 11.16%, respectively. The χ(2) test revealed that there is a significant difference in the positive rate between these 2 groups (P < 0.01). The TP-IgM positive rate in the same group, as detected by the GICA method and the FTA-Abs method, had no significant difference in statistics. However, as detected by the GICA method and the FTA-Abs method, all the samples in serum cure group B and the control group were negative for TP-IgM. The TP-IgM-positive result demonstrated that active T. pallidum remained in the bodies of SSR patients. In summary, the characteristics of GICA TP-IgM correspond to that of FTA-Abs TP-IgM; this can be used as a serologic marker for the relapse and infection of syphilis in place of the conventional FTA-Abs IgM test. PMID:21388769

  14. New ELISA Kits using C3 Binding Glycoprotein from Cuscuta europea Detect Mainly IgM CIC in Rheumatoid Arthritis and Progressive Systemic Sclerosis, but not in Systemic Lupus Erythematosus

    PubMed Central

    Stanilova, Spaska Angelova; Slavov, Emil Slavov

    2003-01-01

    Elevated levels of circulating immune complexes (CIC), containing IgG, IgM or IgA antibodies were detected in the sera of patients with autoimmune diseases. This might indicate a different biological meaning of the three isotypes of immunoglobulin (Ig) in the CIC. Each CIC assay detected only certain classes and subclasses of Ig in CIC material or fixed complement protein. In this study, a new method based on C3binding glycoprotein named CIF-ELISA and a well-known method ANTI-C3 ELISA, were used for quantitative assessment of IgM-CIC, IgG-CIC and IgA-CIC levels in human sera. A modified CIF-ELISA and ANTI-C3 ELISA for simultaneous detection of CIC, containing IgG, IgM and IgA, (stCIC), were also performed. The assays were evaluated on the same specially prepared samples: 55 normal sera, 99 sera from rheumatoid arthritis (RA), 88 sera from systemic lupus erythematosus (SLE), and 27 sera from progressive systemic sclerosis (PSS). We found that the sensitivity of the tests used varied depending on the diseases studied. CIF-ELISA displayed higher sensitivity of IgM-CIC when compared to ANTI-C3 ELISA in RA patients (40.0 and 20.95%, respectively) and PSS (44.43 and 37.04%, respectively). Results for the sensitivity of IgA-CIC were in adverse direction in the RA group (14.28 and 19.05%) and PSS (14.81 and 25.93%) by both methods. It was also established that the concordance of IgM-CIC positives by both methods was 48.84% in RA and 46.67% in PSS, while in SLE it was 18.78%. These results are most probably due to the different assay abilities to detect antibody isotype of the CIC material and help to explain what specific role each Ig isotype in CIC has in the course of the disease. PMID:14768941

  15. A Microarray-Matrix-assisted Laser Desorption/Ionization-Mass Spectrometry Approach for Site-specific Protein N-glycosylation Analysis, as Demonstrated for Human Serum Immunoglobulin M (IgM).

    PubMed

    Pabst, Martin; Kster, Simon Karl; Wahl, Fabian; Krismer, Jasmin; Dittrich, Petra S; Zenobi, Renato

    2015-06-01

    We demonstrate a new approach for the site-specific identification and characterization of protein N-glycosylation. It is based on a nano-liquid chromatography microarray-matrix assisted laser desorption/ionization-MS platform, which employs droplet microfluidics for on-plate nanoliter reactions. A chromatographic separation of a proteolytic digest is deposited at a high frequency on the microarray. In this way, a short separation run is archived into thousands of nanoliter reaction cavities, and chromatographic peaks are spread over multiple array spots. After fractionation, each other spot is treated with PNGaseF to generate two correlated traces within one run, one with treated spots where glycans are enzymatically released from the peptides, and one containing the intact glycopeptides. Mining for distinct glycosites is performed by searching for the predicted deglycosylated peptides in the treated trace. An identified peptide then leads directly to the position of the "intact" glycopeptide clusters, which are located in the adjacent spots. Furthermore, the deglycosylated peptide can be sequenced efficiently in a simple collision-induced dissociation-MS experiment. We applied the microarray approach to a detailed site-specific glycosylation analysis of human serum IgM. By scanning the treated spots with low-resolution matrix assisted laser desorption/ionization-time-of-flight-MS, we observed all five deglycosylated peptides, including the one originating from the secretory chain. A detailed glycopeptide characterization was then accomplished on the adjacent, untreated spots with high mass resolution and high mass accuracy using a matrix assisted laser desorption ionization-Fourier transform-MS. We present the first detailed and comprehensive mass spectrometric analysis on the glycopeptide level for human polyclonal IgM with high mass accuracy. Besides complex type glycans on Asn 395, 332, 171, and on the J chain, we observed oligomannosidic glycans on Asn 563, Asn 402 and minor amounts of oligomannosidic glycans on the glycosite Asn 171. Furthermore, hybrid type glycans were found on Asn 402, Asn 171 and in traces Asn 332. PMID:25802287

  16. Development of a novel protein biochip enabling validation of immunological assays and detection of serum IgG and IgM antibodies against Treponema pallidum pathogens in the patients with syphilis.

    PubMed

    Huang, Na-Li; Ye, Lei; Schneider, Marion E; Du, Yi-Xin; Xu, Yuan-Hong; Fan, Li-Bin; Du, Wei-Dong

    2016-01-15

    In this study, we developed a novel protein biochip methodology that was characterized by dithiobis (succinimidyl undecanoate) (DSU) and specialized for detection of serum IgG and IgM antibodies against Treponema pallidum pathogens in the patients with syphilis, respectively. The biochips were validated by a dimension of atomic force microscope (AFM). The visualized detection limit of IgG antibody on the biochip was 0.39μg/ml. Finally, 286 serum samples from the patients with syphilis were simultaneously tested on the rTpN15-17-47 coated biochips. The results were evaluated in comparison with the assays of T. pallidum particle agglutination (TPPA) and the toluidine red unheated serum test (TRUST). The result demonstrated that the relative positive rate in the 286 patients by biochip was 99.0%, similar to that by TPPA (97.9%, P>0.05) and higher than that by TRUST, (76.2%, P<0.01). The detection specificities were 100% for the biochip and the TPPA and 97.0% for the TRUST. Thus, the protein biochip would provide a useful platform not only for enabling concurrent detection of the infectious antibodies directed against T. pallidum on a larger scale, but also for monitoring therapy modality of the disease. PMID:26364122

  17. Monoclonal IgM rheumatoid factors bind IgG at a discontinuous epitope comprised of amino acid loops from heavy-chain constant-region domains 2 and 3.

    PubMed Central

    Artandi, S E; Calame, K L; Morrison, S L; Bonagura, V R

    1992-01-01

    A combination of site-directed mutagenesis and exon exchange has been used to further define the structure on IgG recognized by monoclonal IgM rheumatoid factors (RFs) from patients with Waldenstrom macroglobulinemia. Most of these RFs bound IgG1, -2, and -4 but not IgG3. For these RFs, His-435 is a critical residue for binding and replacing it with arginine, the residue present in IgG3, destroys or reduces RF binding. However, additional polymorphic sequences in both the heavy-chain constant-region domains (CH) 2 and 3 are important for RF binding. Among the important residues in CH2 are amino acids 252-254 and 309-311, which are conserved among IgG isotypes and comprise two loops of amino acids on the surface of the domain. Therefore, at least three regions, two from CH2 and one from CH3, contribute significantly to the epitope recognized by the RFs. Although this epitope contains many of the same residues as the staphylococcal protein A binding site on IgG, the binding specificities of staphylococcal protein A and monoclonal RFs are not identical. Sera from patients with rheumatoid arthritis contain antibodies directed not only at this epitope but also at other sites on IgG. Images PMID:1370358

  18. De novo 13q12.3-q14.11 deletion involving BRCA2 gene in a patient with developmental delay, elevated IgM levels, transient ataxia, and cerebellar hypoplasia, mimicking an A-T like phenotype.

    PubMed

    Cirillo, Emilia; Romano, Rosa; Romano, Alfonso; Giardino, Giuliana; Durandy, Anne; Nitsch, Lucio; Genesio, Rita; Di Gregorio, Eleonora; Cavalieri, Simona; Abate, Giovanna; Del Vecchio, Luigi; Brusco, Alfredo; Pignata, Claudio

    2012-10-01

    We report on a child with a de novo deletion of approximately 12 Mb detected through array comparative genomic hybridization (CGH). The deletion involved chromosome bands 13q12.3-13q14.11 and determined the loss of ≥50 genes. A second deletion on chromosome 12p11.3p11.22 of 43-167 kb, including about 12 genes, was unlikely of clinical relevance because inherited from the asymptomatic father. The child had developmental delay, dysmorphisms, and many features reminiscent of ataxia-telangiectasia (A-T), as cerebellar ataxia, oculocutaneus telangiectasia, and recurrent upper airway infections. Atraumatic fractures of the metatarsus were noted. Moreover, this is a rare case of 13q deletion syndrome associated with peripheral blood white cells radiosensitivity to bleomycin, reminiscent of what previously reported on X-ray hypersensitivity of fibroblasts from patients with alterations of this chromosome. The immunological evaluation revealed increased IgM serum levels and a low proliferative response to mitogens, PHA, and CD3 cross-linking (CD3 XL). After 12 years of age only a mild dysmetria persisted, while the proliferative response to mitogens became normal by 9 years of age. PMID:22903806

  19. Intrathecally produced IgG and IgM antibodies to recombinant VlsE, VlsE peptide, recombinant OspC and whole cell extracts in the diagnosis of Lyme neuroborreliosis.

    PubMed

    Stanek, Gerold; Lusa, Lara; Ogrinc, Katarina; Markowicz, Mateusz; Strle, Franc

    2014-04-01

    Detection of intrathecally produced specific antibodies (AI) is essential in the diagnosis of Lyme neuroborreliosis (LNB); however, the performance of various newer AI detection methods has not been systematically assessed. Here we assessed and compared advanced test systems for detecting borrelia IgG-AI and IgM-AI. Serum and cerebrospinal fluid (CSF) samples from well-defined LNB and tick-borne encephalitis (TBE) patients, 25 each, were tested with three antibody detection systems, one based on chemiluminescence (CLA) and two based on enzyme-linked immunosorbent assays (ELISA), employing different antigens for detection of IgG and IgM antibodies. In samples from patients with LNB, IgG-AI was detected in 20 samples by CLA, 19 by ELISA1, and 22 by ELISA2, and IgM-AI was detected in 16 samples by CLA, six by ELISA1, and 11 by ELISA2. In samples from TBE patients, IgG-AI was positive in one case by CLA and ELISA2, and in 7 cases by ELISA1, whereas IgM-AI was positive in one case by CLA and in none by ELISA. IgG-AI and IgM-AI were not detected within the first week of disease. Duration of disease correlated with IgG-AI while IgM-AI results were heterogeneous for each test assay. Moreover, the levels of IgG-AI, but not IgM-AI, correlated with protein concentration in CSF. IgG is the relevant immunoglobulin isotype for detecting intrathecal synthesis of borrelia antibodies. The highest sensitivity and specificity were achieved by the antibody detection assay using VlsE IR6 peptide. Detection of IgM-AI yielded heterogenous results and did not support the laboratory diagnosis of LNB. PMID:24363169

  20. Cyprinid Herpesvirus 3 Il10 Inhibits Inflammatory Activities of Carp Macrophages and Promotes Proliferation of Igm+ B Cells and Memory T Cells in a Manner Similar to Carp Il10.

    PubMed

    Piazzon, M Carla; Wentzel, Annelieke S; Tijhaar, Edwin J; Rakus, Krzysztof Ł; Vanderplasschen, Alain; Wiegertjes, Geert F; Forlenza, Maria

    2015-10-15

    Cyprinid herpesvirus 3 (CyHV-3) is the causative agent of a lethal disease of carp and encodes for an Il10 homolog (ORF134). Our previous studies with a recombinant ORF134-deleted strain and the derived revertant strain suggested that cyprinid herpesvirus 3 Il10 (CyHV-3 Il10 [cyhv3Il10]) is not essential for viral replication in vitro, or virulence in vivo. In apparent contrast, cyhv3Il10 is one of the most abundant proteins of the CyHV-3 secretome and is structurally very similar to carp Il10 and also human IL10. To date, studies addressing the biological activity of cyhv3Il10 on cells of its natural host have not been performed. To address the apparent contradiction between the presence of a structurally conserved Il10 homolog in the genome of CyHV-3 and the lack of a clear phenotype in vivo using recombinant cyhv3Il10-deleted viruses, we used an in vitro approach to investigate in detail whether cyhv3Il10 exerts any biological activity on carp cells. In this study, we provide direct evidence that cyhv3Il10 is biologically active and, similarly to carp Il10, signals via a conserved Stat3 pathway modulating immune cells of its natural host, carp. In vitro, cyhv3Il10 deactivates phagocytes with a prominent effect on macrophages, while also promoting proliferation of Igm(+) B cells and memory T cells. Collectively, this study demonstrates a clear biological activity of cyhv3Il10 on cells of its natural host and indicates that cyhv3Il10 is a true viral ortholog of carp Il10. Furthermore, to our knowledge, this is the first report on biological activities of a nonmammalian viral Il10 homolog. PMID:26371255

  1. T cell clones from an X-linked hyper-immunoglobulin (IgM) patient induce IgE synthesis in vitro despite expression of nonfunctional CD40 ligand.

    PubMed

    Life, P; Gauchat, J F; Schnuriger, V; Estoppey, S; Mazzei, G; Durandy, A; Fischer, A; Bonnefoy, J Y

    1994-11-01

    The induction of immunoglobulin E (IgE) switching in B cells requires at least two signals. The first is given by either of the soluble lymphokines interleukin 4 (IL-4) or IL-13, whereas the second is contact dependent. It has been widely reported that a second signal can be provided by the CD40 ligand (CD40L) expressed on the surface of T cells, mast cells, and basophils. A defect in the CD40L has been shown recently to be responsible for the lack of IgE, IgA, and IgG, characteristic of the childhood X-linked immunodeficiency, hyper IgM syndrome (HIGM1). IgE can however be detected in the serum of some HIGM1 patients. In this study, we isolated T cell clones and lines using phytohemagglutinin (PHA) and allergen, respectively, from the peripheral blood of one such patient who expressed a truncated form of CD40L, and investigated their ability to induce IgE switching in highly purified, normal tonsillar B cells in vitro. Unexpectedly, 4 of 12 PHA clones tested induced contact-dependent IgE synthesis in the presence of exogenous IL-4. These clones were also shown to strongly upregulated IL-4-induced germline epsilon RNA and formed dense aggregates with B cells. Of the four helper clones, three were CD8+, of which two were characteristic of the T helper cell 2 (Th2) subtype. Two allergen-specific HIGM1 T cell lines, both of the Th0 subtype, could also drive IgE synthesis when prestimulated using specific allergen. All clones and lines were negative for surface expression of CD40L, and the mutated form of CD40L was confirmed for a representative clone by RNase protection assay and sequencing. The IgE helper activity could not be attributed to membrane tumor necrosis factor alpha (TNF-alpha) although it was strongly expressed on activated clones, and the addition of neutralizing anti-TNF-alpha antibody did not abrogate IgE synthesis. These results therefore suggest the involvement of T cell surface molecules other than CD40L in the induction of IgE synthesis, and that these molecules may also be implicated in other aspects of T-B cell interactions. PMID:7964460

  2. Establishment of an Algorithm Using prM/E- and NS1-Specific IgM Antibody-Capture Enzyme-Linked Immunosorbent Assays in Diagnosis of Japanese Encephalitis Virus and West Nile Virus Infections in Humans.

    PubMed

    Galula, Jedhan U; Chang, Gwong-Jen J; Chuang, Shih-Te; Chao, Day-Yu

    2016-02-01

    The front-line assay for the presumptive serodiagnosis of acute Japanese encephalitis virus (JEV) and West Nile virus (WNV) infections is the premembrane/envelope (prM/E)-specific IgM antibody-capture enzyme-linked immunosorbent assay (MAC-ELISA). Due to antibody cross-reactivity, MAC-ELISA-positive samples may be confirmed with a time-consuming plaque reduction neutralization test (PRNT). In the present study, we applied a previously developed anti-nonstructural protein 1 (NS1)-specific MAC-ELISA (NS1-MAC-ELISA) on archived acute-phase serum specimens from patients with confirmed JEV and WNV infections and compared the results with prM/E containing virus-like particle-specific MAC-ELISA (VLP-MAC-ELISA). Paired-receiver operating characteristic (ROC) curve analyses revealed no statistical differences in the overall assay performances of the VLP- and NS1-MAC-ELISAs. The two methods had high sensitivities of 100% but slightly lower specificities that ranged between 80% and 100%. When the NS1-MAC-ELISA was used to confirm positive results in the VLP-MAC-ELISA, the specificity of serodiagnosis, especially for JEV infection, was increased to 90% when applied in areas where JEV cocirculates with WNV, or to 100% when applied in areas that were endemic for JEV. The results also showed that using multiple antigens could resolve the cross-reactivity in the assays. Significantly higher positive-to-negative (P/N) values were consistently obtained with the homologous antigens than those with the heterologous antigens. JEV or WNV was reliably identified as the currently infecting flavivirus by a higher ratio of JEV-to-WNV P/N values or vice versa. In summary of the above-described results, the diagnostic algorithm combining the use of multiantigen VLP- and NS1-MAC-ELISAs was developed and can be practically applied to obtain a more specific and reliable result for the serodiagnosis of JEV and WNV infections without the need for PRNT. The developed algorithm should provide great utility in diagnostic and surveillance activities in which test accuracy is of utmost importance for effective disease intervention. PMID:26659204

  3. Securing PCs and Data in Libraries and Schools: A Handbook with Menuing, Anti-Virus, and Other Protective Software.

    ERIC Educational Resources Information Center

    Benson, Allen C.

    This handbook is designed to help readers identify and eliminate security risks, with sound recommendations and library-tested security software. Chapter 1 "Managing Your Facilities and Assessing Your Risks" addresses fundamental management responsibilities including planning for a secure system, organizing computer-related information, assessing

  4. Securing PCs and Data in Libraries and Schools: A Handbook with Menuing, Anti-Virus, and Other Protective Software.

    ERIC Educational Resources Information Center

    Benson, Allen C.

    This handbook is designed to help readers identify and eliminate security risks, with sound recommendations and library-tested security software. Chapter 1 "Managing Your Facilities and Assessing Your Risks" addresses fundamental management responsibilities including planning for a secure system, organizing computer-related information, assessing…

  5. Detection of immunoglobulin M (IgM), IgA, and IgG Norwalk virus-specific antibodies by indirect enzyme-linked immunosorbent assay with baculovirus-expressed Norwalk virus capsid antigen in adult volunteers challenged with Norwalk virus.

    PubMed Central

    Gray, J J; Cunliffe, C; Ball, J; Graham, D Y; Desselberger, U; Estes, M K

    1994-01-01

    Pre- and postexposure sera collected from 17 adult volunteers challenged with Norwalk virus as described previously (D. Y. Graham, X. Jiang, T. Tanaka, A. Opekun, P. Madore, and M. K. Estes, J. Infect. Dis. 170:34-43, 1994) were examined for Norwalk virus-specific immunoglobulin M (IgM), IgA, and IgG by indirect enzyme-linked immunosorbent assays with recombinant Norwalk virus antigen bound to the solid phase. Sixteen of the 17 volunteers had evidence of past infection, all presenting with preexisting IgG antibody of high avidity; only one volunteer had no evidence of previous infection. Virus infection was detected in 14 of the 16 volunteers with evidence of past infection, and 9 of the infected volunteers had symptomatic illness. A significant rise in both virus-specific IgA and IgG titers was detected after challenge in all of the volunteers who became ill. Five of the asymptomatic volunteers who were infected had rising titers of virus-specific IgG, but only two of the five had a concomitant rise in their virus-specific IgA antibody titers. Antibody rises were detectable in eight of nine ill volunteers 8 to 11 days after challenge but in the asymptomatic volunteers only after more than 15 days had elapsed. Virus-specific IgM was detected after challenge in all 14 infected volunteers. Between symptomatic and asymptomatic volunteers there were no significant differences in titers of virus-specific IgG and IgA in serum before challenge; however, there were significantly higher titers in symptomatic volunteers between 8 and > 90 days after challenge for virus-specific IgG and 8 and 24 days after challenge for virus-specific IgA. PMID:7883902

  6. Constraining the Thermal State of the IGM at z~20

    NASA Astrophysics Data System (ADS)

    Greenhill, Lincoln J.; LEDA Collaboration

    2015-01-01

    One of the great challenges of observational cosmology is to trace the thermal history of the Universe during the Dark Age, before the first stars, and immediately following. Theory suggests that the 21 cm transition of Hydrogen can serve as a unique thermometer for the intergalactic medium during this era, and thermal evolution is believed to have depended on a relatively small set of fundamental processes. Detection of the 21cm transition at redshift ~20 should enable strong tests of cosmological models. The ground-based Large Aperture Experiment to Detect the Dark Age (LEDA) is working to establish direct constraint on the thermal history through detection of sky-averaged spectral-line absorption of the Cosmic Microwave Background by the 21cm transition. I will present the latest results from LEDA obtained using stations of the Long Wavelength Array facility and outline technical milestones such as construction of one of the largest radio astronomical correlators in the world and instantaneous confusion-limited images of the full sky (2pi steradian) below 80 MHz.

  7. [Presence of IgM antibodies for Leptospira interrogans in wild animals from Tocantins State, 2002].

    PubMed

    de Souza Jnior, Milton Formiga; Lobato, Zlia Ins Portela; Lobato, Francisco Carlos Faria; Moreira, Elvio Carlos; de Oliveira, Rogrio Rodrigues; Leite, Geysa Goulart; Freitas, Theonys Digenes; de Assis, Ronnie Antunes

    2006-01-01

    Four hundred and twenty-seven serum samples of wild animals were tested against 18 serovars of Leptospira interrogans. Of 286 samples of Cebus apella, 46 (16.1%) were positive for the serovars pomona, brasiliensis, mini, swajizak, grippotyphosa, sarmin, fluminense, autumnalis, hebdomadis, guaratuba, javanica and icterohaemorrhagiae. Of 82 samples of Alouatta caraya, 2 (2.4%) were positive for the serovars mangus and fluminense. Of 31 samples of Nasua nasua, 4 (12.9%) were positive for the serovars fluminense and javanica, and of 10 samples of Cerdocyon thous, 2 (20 %) were positive for the serovars fluminense and brasiliensis. Seven samples of Dasyprocta sp, 6 of Tamandua tetradactyla and 5 of Euphractus sexcintus did not present reactivity. PMID:16906258

  8. Direct in vivo injection of 131I-GMS and its distribution and excretion in rabbit

    PubMed Central

    Ma, Yu; Wan, Yi; Luo, Dong-Hui; Duan, Li-Geng; Li, Lin; Xia, Chuan-Qin; Chen, Xiao-Li

    2010-01-01

    AIM: To explore the distribution and metabolism of 131I-gelatin microspheres (131I-GMSs) in rabbits after direct injection into rabbits’ livers. METHODS: Twenty-eight healthy New Zealand rabbits were divided into seven groups, with four rabbits per group. Each rabbit’s hepatic lobes were directly injected with 41.336 ± 5.106 MBq 131I-GMSs. Each day after 131I-GMSs administration, 4 rabbits were randomly selected, and 250 μL of serum was collected for γ count. Hepatic and thyroid functions were tested on days 1, 4, 8, 16, 24, 32, 48 and 64 after 131I-GMSs administration. Single-photon emission computed tomography (SPECT) was taken for each group on days 0, 1, 4, 8, 16, 24, 32, 48, 64 after 131I-GMSs administration. A group of rabbits were sacrificed respectively on days 1, 4, 16, 24, 32, 48, 64 after 131I-GMSs administration. Their livers were taken out for histological examination. RESULTS: After 131I-GMSs administration, the nuclide was collected in the hepatic area with microspheres. The radiation could be detected on day 48 after 131I-GMSs administration, and radiography could be seen in thyroid areas in SPECT on days 4, 8, 16 and 24. One day after 131I-GMSs administration, the liver function was damaged but recovered 4 d later. Eight days after 131I-GMSs administration, the levels of free triiodothyronine and free thyroxin were reduced, which restored to normal levels on day 16. Histological examination showed that the microspheres were degraded to different degrees at 24, 32 and 48 d after 131I-GMSs administration. The surrounding parts of injection points were in fibrous sheathing. No microspheres were detected in histological examination on day 64 after 131I-GMSs administration. CONCLUSION: Direct in vivo injection of 131I-GMSs is safe in rabbits. It may be a promising method for treatment of malignant tumors. PMID:20440852

  9. Integrated Grid Modeling System (IGMS) for Combined Transmission and Distribution Simulation

    SciTech Connect

    Palmintier, Bryan

    2015-07-28

    This presentation discusses the next-generation analysis framework for full-scale transmission and distribution modeling that supports millions of highly distributed energy resources, and also discusses future directions for transmission and distribution.

  10. Production and characterization of IgM monoclonal antibodies against hyphal antigens of Stachybotrys species

    EPA Science Inventory

    Stachybotrys is a hydrophilic fungal genus that is well known for its ability to colonize water-damaged building materials in indoor environments. Personal exposure to Stachybotrys chartarum allergens, mycotoxins, cytolytic peptides, and other immunostimulatory macromolecules has...

  11. MOSAIC at the E-ELT: A multi-object spectrograph for astrophysics, IGM and cosmology

    NASA Astrophysics Data System (ADS)

    Hammer, F.; Barbuy, B.; Cuby, J. G.; Kaper, L.; Morris, S.; Evans, C. J.; Jagourel, P.; Dalton, G.; Rees, P.; Puech, M.; Rodrigues, M.; Pearson, D.; Disseau, K.

    2014-08-01

    The Universe is comprised of hundreds of billions of galaxies, each populated by hundreds of billions of stars. Astrophysics aims to understand the complexity of this almost incommensurable number of stars, stellar clusters and galaxies, including their spatial distribution, formation, and current interactions with the interstellar and intergalactic media. A considerable fraction of astrophysical discoveries require large statistical samples, which can only be addressed with multi-object spectrographs (MOS). Here we introduce the MOSAIC study of an optical/near-infrared MOS for the European Extremely Large Telescope (E-ELT), which has capabilities specified by science cases ranging from stellar physics and exoplanet studies to galaxy evolution and cosmology. Recent studies of critical technical issues such as sky-background subtraction and multi-object adaptive optics (MOAO) have demonstrated that such a MOS is feasible with current technology and techniques. In the 2020s the E-ELT will become the world's largest optical/IR telescope, and we argue that it has to be equipped as soon as possible with a MOS. MOSAIC will provide a vast discovery space, enabled by a multiplex of 200 and spectral resolving powers of R = 5 000 and 20 000. MOSAIC will also offer the unique capability of 10-to-20 `high-definition' (MOAO) integral-field units, optimised to investigate the physics of the sources of reionisation, providing the most efficient follow-up of observations with the James Webb Space Telescope (JWST). The combination of these modes will enable the study of the mass-assembly history of galaxies over cosmic time, including high-redshift dwarf galaxies and studies of the distribution of the intergalactic medium. It will also provide spectroscopy of resolved stars in external galaxies at unprecedented distances, from the outskirts of the Local Group for main-sequence stars, to a significant volume of the local Universe, including nearby galaxy clusters, for luminous red supergiants.

  12. AGN Activity and IGM Heating in the Fossil Cluster RX J1416.4+2315

    NASA Astrophysics Data System (ADS)

    Miraghaei, H.; Khosroshahi, H. G.; Sengupta, C.; Raychaudhury, S.; Jetha, N. N.; Abbassi, S.

    2015-12-01

    We study active galactic nucleus (AGN) activity in the fossil galaxy cluster RX J1416.4+2315. Radio observations were carried out using the Giant Metrewave Radio Telescope at two frequencies, 1420 and 610 MHz. A weak radio lobe that extends from the central nucleus is detected in the 610 MHz map. Assuming the radio lobe originated from the central AGN, we show that the energy injection into the intergalactic medium is only sufficient to heat up the central 50 kpc within the cluster core, while the cooling radius is larger (∼130 kpc). In the hardness ratio map, three low energy cavities have been identified. No radio emission is detected for these regions. We evaluated the power required to inflate the cavities and showed that the total energy budget is sufficient to offset the radiative cooling. We showed that the initial conditions would change the results remarkably. Furthermore, the efficiency of the Bondi accretion in powering the AGN has been estimated.

  13. Genetics Home Reference: X-linked hyper IgM syndrome

    MedlinePLUS

    ... have low levels of white blood cells called neutrophils (neutropenia). Affected individuals may develop autoimmune disorders, neurologic ... inherited ; ligand ; lymphoma ; mutation ; nervous system ; neurologic ; neutropenia ; neutrophils ; pneumonia ; protein ; receptor ; recessive ; sex chromosomes ; sinus ; sinusitis ; ...

  14. Analysis of IgM antibody production and repertoire in a mouse model of Sjgren's syndrome.

    PubMed

    Kramer, Jill M; Holodick, Nichol E; Vizconde, Teresa C; Raman, Indu; Yan, Mei; Li, Quan-Zhen; Gaile, Daniel P; Rothstein, Thomas L

    2016-02-01

    This study tested the hypothesis that B cells from salivary tissue are distinct in terms of proliferative capacity, immunoglobulin M secretion, repertoire, and autoantibody enrichment in Sjgren's syndrome. We sorted purified B cells from the spleen, cervical lymph nodes, and submandibular glands of a primary Sjgren's syndrome mouse model (Id3(-/-)). Enzyme-linked immunospot and proliferation assays were performed with stimulated B cells. We single-cell sorted B cells from the spleen, cervical lymph nodes, and submandibular gland tissue from Sjgren's syndrome mice and sequenced immunoglobulin M heavy-chain variable regions. Finally, autoantigen arrays were performed using immunoglobulin M derived from sera, cervical lymph nodes, spleens, and submandibular gland tissue of Id3(-/-) animals. Results suggest B cells from salivary tissue of Sjgren's syndrome mice are similar to those from secondary immune sites in terms of proliferative and secretory capacity. However, differences in repertoire usage, heavy chain complementarity-determining region 3 length, mutational frequency, and N region addition were observed among B cells derived from submandibular gland, cervical lymph node, and spleen tissue. Moreover, autoantigen array data show immunoglobulin M from salivary B cells have enriched specificity for Ro (Sjgren's syndrome A) and La (Sjgren's syndrome B). All together, these data suggest salivary B cells have unique repertoire characteristics that likely influence autoantigen binding and contribute to Sjgren's syndrome disease in a tissue-specific manner. PMID:26382297

  15. How to Keep Your Campus Safe from Infection

    ERIC Educational Resources Information Center

    Brown, Scott

    2005-01-01

    In this article, the author explains how antivirus programs work. He also explains how performances of various antivirus programs vary from one to another. He also takes a look at 13 antivirus programs and explains which of these will keep computers protected. These programs include: (1) Sophos Anti-Virus Version 3.86.2; (2) McAfee VirusScan 9.0;

  16. How to Keep Your Campus Safe from Infection

    ERIC Educational Resources Information Center

    Brown, Scott

    2005-01-01

    In this article, the author explains how antivirus programs work. He also explains how performances of various antivirus programs vary from one to another. He also takes a look at 13 antivirus programs and explains which of these will keep computers protected. These programs include: (1) Sophos Anti-Virus Version 3.86.2; (2) McAfee VirusScan 9.0;…

  17. [Detection of the markers of herpes simplex virus and cytomegalovirus in newborns and infants].

    PubMed

    Medzhidova, M G; Adueva, S M; Fedorova, N E; Klimova, R R; Vorontsova, Iu N; Degtiareva, M V; Degtiarev, D N; Volodin, N N; Aliamovskaia, G A; Keshishchian, E S; Malakhova, M V; Il'ina, E N; Govorun, V M; Zemlianaia, N Iu; Shcherbo, S V; Asadi Mobarkhan, S M; Asadi Mobarkhan, A Kh; Kushch, A A

    2005-01-01

    A total of 111 children suspected for herpesvirus infection were examined. In blood and urine samples the infectious activity of herpes simplex virus (HSV) and cytomegalovirus (CMV) was detected by the rapid culture method (RCM) and the presence of virus DNA--by the polymerase chain reaction (PCR). HSV and/or CMV were detected by two laboratory methods in 57 examined children (51%). Of these, in 18 children (16.2%) both HSV and CMV were detected. The coincidence of the results of the detection of HSV and CMV by these two methods was observed in 72.4% and 75.2% of cases respectively. The comparative analysis of the detection of anti-CMV IgG and IgM was made with the use of commercial test systems produced bythe following manufacturers: "Vector-Best" and "Bioservice" (Russia), "HUMAN" and "Boehringer" (Germany). The effective detection of both anti-CMV (IgG and IgM) was ensured by the test systems "Boehringer". The test system "Vector-Best" for anti-CMV IgG proved to be not inferior as regards sensitivity and specificity. The German test systems demonstrated the highest specificity in the detection of low-avid antibodies. The data obtained in this study indicate that the detection rate of HSV and CMV markers in newborns and infants suspected for herpesvirus infection was, on the average, 20 - 40%. Reliable diagnostics in newborns and infants is possible only in the presence of the combination of at least 2 serological tests (the determination of antivirus IgM and IgG avidity) and 2 methods for the detection of direct herpesvirus markers (PCR and RCM). PMID:16279541

  18. The IgM antigen receptor of B lymphocytes is associated with prohibitin and a prohibitin-related protein.

    PubMed Central

    Terashima, M; Kim, K M; Adachi, T; Nielsen, P J; Reth, M; Khler, G; Lamers, M C

    1994-01-01

    The two major classes of antigen receptors on murine B lymphocytes, mIgM and mIgD, are both contained in a complex with two additional molecules, Ig-alpha and Ig-beta, which permit signal transduction. Accordingly, early biochemical events after antigen binding to either receptor are similar; biological effects, however, are different. Here, we describe three newly discovered intracellular proteins of 32, 37 and 41 kDa molecular mass, that are non-covalently associated with mIgM, but not with mIgD. These proteins coprecipitate with mIgM in Triton X-100 and Nonidet P-40, but not in digitonin lysates. In addition, mIgM is to some extent associated with 29 and 31 kDa proteins that are predominantly associated with mIgD (see accompanying paper). Amino acid sequencing of p32 and p37 identified p32 as mouse prohibitin; this was corroborated by Western blot analysis with antibodies specific for rat prohibitin. p37 is a newly discovered protein. cDNA clones for both proteins were isolated and sequenced. The deduced amino acid sequence of p32 is identical to that of rat prohibitin. p37 is highly homologous to p32. Since prohibitin was identified as an inhibitor of cell proliferation, its association with mIgM, but not mIgD, could explain the different biological events elicited after engagement of each receptor. Images PMID:8070406

  19. Development and validation of an ELISA kit (YF MAC-HD) to detect IgM to yellow fever virus.

    PubMed

    Basile, Alison Jane; Goodman, Christin; Horiuchi, Kalanthe; Laven, Janeen; Panella, Amanda J; Kosoy, Olga; Lanciotti, Robert S; Johnson, Barbara W

    2015-12-01

    Yellow fever virus (YFV) is endemic in tropical and sub-tropical regions of the world, with around 180,000 human infections a year occurring in Africa. Serologic testing is the chief laboratory diagnostic means of identifying an outbreak and to inform the decision to commence a vaccination campaign. The World Health Organization disseminates the reagents for YFV testing to African reference laboratories, and the US Centers for Disease Control and Prevention (CDC) is charged with producing and providing these reagents. The CDC M-antibody capture ELISA is a 2-day test, requiring titration of reagents when new lots are received, which leads to inconsistency in testing and wastage of material. Here we describe the development of a kit-based assay (YF MAC-HD) based upon the CDC method, that is completed in approximately 3.5h, with equivocal samples being reflexed to an overnight protocol. The kit exhibits >90% accuracy when compared to the 2-day test. The kits were designed for use with a minimum of equipment and are stored at 4°C, removing the need for freezing capacity. This kit is capable of tolerating temporary sub-optimal storage conditions which will ease shipping or power outage concerns, and a shelf life of >6 months was demonstrated with no deterioration in accuracy. All reagents necessary to run the YF MAC-HD are included in the kit and are single-use, with 8 or 24 sample options per kit. Field trials are envisioned for the near future, which will enable refinement of the method. The use of the YF MAC-HD is anticipated to reduce materials wastage, and improve the quality and consistency of YFV serologic testing in endemic areas. PMID:26342907

  20. Real-Time PCR for Measles Virus Detection on Clinical Specimens with Negative IgM Result in Morocco

    PubMed Central

    Benamar, Touria; Tajounte, Latifa; Alla, Amal; Khebba, Fatima; Ahmed, Hinda; Mulders, Mick N.; Filali-Maltouf, Abdelkarim; El Aouad, Rajae

    2016-01-01

    Since the confirmation of measles cases represents an important indicator regarding the performance of the measles-elimination program, the aim of this study was to evaluate the effectiveness of the routine procedures followed in Morocco for the laboratory confirmation of measles cases. Suspected cases reported between January 2010 and December 2012 were assessed for the timeliness of the sample collection, occurrence of measles clinical symptoms, and the results of the laboratory diagnoses. For 88% of the 2,708 suspected cases, a clinical specimen was collected within 7d of rash onset, of which 50% were IgM-positive and 2.6% were equivocal. The measles symptoms were reported in 91.4% of the cases; the occurrence of symptoms showed a positive association with the serological results (odds ratio [OR] = 2.9883, 95% confidence interval [CI] 2.2238–4.0157). Of the negative samples, 52% (n = 116) tested positive by real-time polymerase chain reaction (PCR). These results are in favor of using molecular detection to complement serological diagnosis in the context of measles surveillance approach in Morocco. In addition, the introduction of additional laboratory methods for differential diagnosis is required for the final classification of suspected cases with maculopapular rash and fever in the context of the measles elimination program. PMID:26812434

  1. Epitope analysis of peanut allergen Ara h1 with oligoclonal IgM antibody from human B-lymphoblastoid cells.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To analyze epitopes of peanut allergen Ara h1, Epstein-Barr virus-transformed human peripheral oligoclonal B-cells were cultured to obtain antibodies to Ara h1. The combined reaction pattern with six oligoclonal antibodies showed there were six antibody binding areas named a to f in Ara h1. We found...

  2. From CODEX to ESPRESSO to HIRES@E-ELT: a view on cosmology and fundamental physics from the IGM perspective

    NASA Astrophysics Data System (ADS)

    Cristiani, S.; Cupani, G.; D'Odorico, V.; Di Marcantonio, P.; Haehnelt, M.; Maiolino, R.; Marconi, A.; Martins, C.; Mgevand, D.; Molaro, P.; Murphy, M. T.; Origlia, L.; Pepe, F.

    The Italian community, thanks to the strong technological and scientific tradition in the field of high-resolution spectroscopy and the study of the Intergalactic Medium, has played a key role in the conception of a high-resolution spectrograph for the new generation of giant telescopes (initially focused on the COsmic Dynamics EXperiment at OWL). This expertise is being exploited in the construction of a precursor: the ESPRESSO instrument that will start operations at the ESO VLT in 2017 and will pave the way to the HIRES instrument at the E-ELT. Here we discuss the role that the (evolving) scientific themes of cosmology and fundamental physics - from the Intergalactic Medium perspective - have played and are playing to shape the E-ELT high resolution instrument.

  3. Real-Time PCR for Measles Virus Detection on Clinical Specimens with Negative IgM Result in Morocco.

    PubMed

    Benamar, Touria; Tajounte, Latifa; Alla, Amal; Khebba, Fatima; Ahmed, Hinda; Mulders, Mick N; Filali-Maltouf, Abdelkarim; El Aouad, Rajae

    2016-01-01

    Since the confirmation of measles cases represents an important indicator regarding the performance of the measles-elimination program, the aim of this study was to evaluate the effectiveness of the routine procedures followed in Morocco for the laboratory confirmation of measles cases. Suspected cases reported between January 2010 and December 2012 were assessed for the timeliness of the sample collection, occurrence of measles clinical symptoms, and the results of the laboratory diagnoses. For 88% of the 2,708 suspected cases, a clinical specimen was collected within 7d of rash onset, of which 50% were IgM-positive and 2.6% were equivocal. The measles symptoms were reported in 91.4% of the cases; the occurrence of symptoms showed a positive association with the serological results (odds ratio [OR] = 2.9883, 95% confidence interval [CI] 2.2238-4.0157). Of the negative samples, 52% (n = 116) tested positive by real-time polymerase chain reaction (PCR). These results are in favor of using molecular detection to complement serological diagnosis in the context of measles surveillance approach in Morocco. In addition, the introduction of additional laboratory methods for differential diagnosis is required for the final classification of suspected cases with maculopapular rash and fever in the context of the measles elimination program. PMID:26812434

  4. Cholera toxin as a mucosal adjuvant for respiratory antibody responses in mice.

    PubMed

    Liang, X P; Lamm, M E; Nedrud, J G

    1989-01-01

    Cholera toxin was investigated as an adjuvant for anti-virus antibody responses in the respiratory mucosa of mice. Two methods of applying cholera toxin were evaluated: oral administration and intranasal administration. Oral immunization with Sendai virus in the presence of cholera toxin effectively primed for respiratory anti-viral antibody responses, whereas oral immunization with Sendai virus alone was ineffective in this respect. In nasal washes, IgA was the predominant anti-viral antibody enhanced by oral cholera toxin; in bronchoalveolar washes, the enhanced anti-viral antibodies included IgG, IgA, and IgM. Effects of direct administration of cholera toxin to the respiratory mucosa on respiratory anti-viral antibody responses depended on the method of anesthesia used during immunization. With inhalation anesthesia (ether), cholera toxin had no adjuvant effect on respiratory antibody responses to coadministered Sendai virus. In contrast, under parenteral anesthesia (i.e., intraperitoneal ketamine), mice which received cholera toxin and Sendai virus via the respiratory tract showed significantly higher anti-viral IgA and IgG antibody titers in nasal washes and IgG antibody in bronchoalveolar washes than mice which received the virus only. PMID:2561961

  5. Architecture for removable media USB-ARM

    SciTech Connect

    Shue, Craig A.; Lamb, Logan M.; Paul, Nathanael R.

    2015-07-14

    A storage device is coupled to a computing system comprising an operating system and application software. Access to the storage device is blocked by a kernel filter driver, except exclusive access is granted to a first anti-virus engine. The first anti-virus engine is directed to scan the storage device for malicious software and report results. Exclusive access may be granted to one or more other anti-virus engines and they may be directed to scan the storage device and report results. Approval of all or a portion of the information on the storage device is based on the results from the first anti-virus engine and the other anti-virus engines. The storage device is presented to the operating system and access is granted to the approved information. The operating system may be a Microsoft Windows operating system. The kernel filter driver and usage of anti-virus engines may be configurable by a user.

  6. Evaluación de Anticuerpos Desarrollados Contra la Proteína Recombinante de la Cápside del Virus Tristeza de los Cítricos

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Polyclonal antibodies specific for the recombinant coat protein (rCP) p25 gene of (Citrus tristeza virus = CTV), were developed for isolates MX08 and MX14 from México and B227 from India. The reactivity of rCP antibodies was evaluated using healthy and CTV infected tissue. The combination of rCP ant...

  7. CD40 agonist antibody mediated improvement of chronic Cryptosporidium infection in patients with X-linked hyper IgM syndrome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    X-linked hyper-IgM syndrome (XHM) is a combined immune deficiency disorder caused by mutations in CD40 ligand. We tested CP-870,893, a human CD40 agonist monoclonal antibody, in the treatment of two XHM patients with biliary Cryptosporidiosis. CP-870,893 activated B cells and APCs in vitro, restori...

  8. Unique dose-dependent effects of the human pregnancy hormone estriol on the ratio of blood IgM to IgG in female mice.

    PubMed

    Ding, Jian; Zhu, Bao-Ting

    2016-01-01

    The present study aimed to investigate the dose-dependent modulating effect of estriol (E3), an estrogen predominantly produced during human pregnancy, on antigen?induced production of specific antibodies in female BALB/c mice. The animals were immunized either with bovine serum albumin (BSA) or the pneumococcal polysaccharide serotype-14 (PPS-14), and the levels of specific serum antibodies were determined using ELISA kits. E3 was found to have very different effects on antigen-induced production of specific antibodies in animals immunized with these two antigens. While E3 stimulated the production of PPS-14-specific antibodies, it suppressed the production of BSA-specific antibodies. The results also demonstrated that the modulating effect of E3 on the production of antigen?specific antibodies depends on the dose of E3 used. For BSA?induced antibody production, E3 had a dose?dependent inhibitory effect, whereas for PPS?14?specific antibody (Ab) production, E3 exerted the strongest stimulation at a lower dose, and produced less stimulation at higher doses. E3 caused thymus atrophy in animals immunized with either PPS?14 or BSA, but only induced spleen atrophy in BSA?injected mice. These observations suggest that E3 increases the ability of a pregnant female to avoid bacterial infections while decreasing the incidence of autoimmune responses against circulating components from either the fetus or pregnant female. PMID:26531070

  9. Field Evaluation and Impact on Clinical Management of a Rapid Diagnostic Kit That Detects Dengue NS1, IgM and IgG

    PubMed Central

    Andries, Anne-Claire; Duong, Veasna; Ngan, Chantha; Ong, Sivuth; Huy, Rekol; Sroin, Kim Kim; Te, Vantha; Y, Bunthin; Try, Patrich Lorn; Buchy, Philippe

    2012-01-01

    Background Dengue diagnosis is complex and until recently only specialized laboratories were able to definitively confirm dengue infection. Rapid tests are now available commercially making biological diagnosis possible in the field. The aim of this study was to evaluate a combined dengue rapid test for the detection of NS1 and IgM/IgG antibodies. The evaluation was made prospectively in the field conditions and included the study of the impact of its use as a point-of-care test for case management as well as retrospectively against a panel of well-characterized samples in a reference laboratory. Methodology/Principal Findings During the prospective study, 157 patients hospitalized for a suspicion of dengue were enrolled. In the hospital laboratories, the overall sensitivity, specificity, PPV and NPV of the NS1/IgM/IgG combination tests were 85.7%, 83.9%, 95.6% and 59.1% respectively, whereas they were 94,4%, 90.0%, 97.5% and 77.1% respectively in the national reference laboratory at Institut Pasteur in Cambodia. These results demonstrate that optimal performances require adequate training and quality assurance. The retrospective study showed that the sensitivity of the combined kit did not vary significantly between the serotypes and was not affected by the immune status or by the interval of time between onset of fever and sample collection. The analysis of the medical records indicates that the physicians did not take into consideration the results obtained with the rapid test including for care management and use of antibiotic therapy. Conclusions In the context of our prospective field study, we demonstrated that if the SD Bioline Dengue Duo kit is correctly used, a positive result highly suggests a dengue case but a negative result doesn't rule out a dengue infection. Nevertheless, Cambodian pediatricians in their daily practice relied on their clinical diagnosis and thus the false negative results obtained did not directly impact on the clinical management. PMID:23301110

  10. Drive-by-Downloads

    SciTech Connect

    Narvaez, Julia; Endicott-Popovsky, Barbara E.; Seifert, Christian; Aval, Chiraag U.; Frincke, Deborah A.

    2010-02-01

    Abstract: Drive-by-downloads are malware that push, and then execute, malicious code on a client system without the user's consent. The purpose of this paper is to introduce a discussion of the usefulness of antivirus software for detecting the installation of such malware, providing groundwork for future studies. Client honeypots collected drive-by malware which was then evaluated using common antivirus products. Initial analysis showed that most of such antivirus products identified less than 70% of these highly polymorphic malware programs. Also, it was observed that the antivirus products tested, even when successfully detecting this malware, often failed to classify it, leading to the conclusion that further work could involve not only developing new behavioral detection technologies, but also empirical studies that improve general understanding of these threats. Toward that end, one example of malicious code was analyzed behaviorally to provide insight into next steps for the future direction of this research.

  11. 78 FR 9386 - Procurement List; Proposed Additions and Deletions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-08

    ...-9694--USB 2.0 Hard Drive, Portable, 320G NSN: 7045-01-599-9345--USB Flash Drive, 256-Bit AES Encryption, Level 3 Encrypted, Anti-Virus, 4GB NSN: 7045-01-599-9346--USB Flash Drive, 256-Bit AES Encryption, Level 3 Encrypted, Anti-Virus, 32GB NSN: 7045-01-599-9348--USB Flash Drive, 256-Bit AES Encryption,...

  12. [IgG, IgM, IgA, secretory IgA and the complement components C3, C4 and C9 in the large intestine in nonspecific ulcerative colitis and Crohn disease].

    PubMed

    Konovich, E A; Kirkin, B V; Khalif, I L

    1987-01-01

    The immunohistological study of the large intestines excised from 20 patients with ulcerous colitis and Crohn's disease was made with the use of the indirect immunofluorescence test. A considerable increase in the number of IgG immunocytes has been noted in the lamina propria of the mucous membrane, especially in infiltrations around ulcers. In cases of a highly active inflammatory process accompanied by the pronounced destruction of the epithelium, IgG and C3, C4, C9 were detected in the epithelium of crypts and in blood vessels of the mucous membrane and the submucosa. One-third of the patients showed a decrease in the number of crypts with secretory and serum IgA. The authors suggest that immune complexes take part in maintaining the chronic inflammatory process. PMID:3564783

  13. Amino acid sequence of the Fv region of a human monoclonal IgM (protein WEA) with antibody activity against 3,4-pyruvylated galactose in Klebsiella polysaccharides K30 and K33.

    PubMed Central

    Goi, F; Frangione, B

    1983-01-01

    We have determined the amino acid sequence of the Fv [variable heavy (VH) and variable light (VL)] region of a human monoclonal IgM-kappa with antibody activity against 3,4-pyruvylated galactose, isolated from the plasma of patient WEA with Waldenstrm macroglobulinemia. The VH region has 114 residues, belongs to subgroup III, and has a very short third complementarity-determining region (CDR3), probably due to a small D segment/or an unusual D-J rearrangement (D, diversity; J, joining). The VL region has 108 residues and belongs to subgroup V kappa I. Compared to other members of the human VHIII and V kappa I families, WEA Fv does not appear to have significant differences within the framework residues but has unique CDRs that might be responsible for the particular antibody activity. Another IgM-kappa (GAL), which has an as-yet-undetermined antibody activity, shares a striking homology in V kappa with WEA, including an identical CDR1. PMID:6410398

  14. Cloning and expression of Rift Valley fever virus nucleocapsid (N) protein and evaluation of a N-protein based indirect ELISA for the detection of specific IgG and IgM antibodies in domestic ruminants.

    PubMed

    Fafetine, Jos Manuel; Tijhaar, Edwin; Paweska, Janusz T; Neves, Lus C B G; Hendriks, Judith; Swanepoel, Robert; Coetzer, J A W; Egberink, Herman F; Rutten, Victor P M G

    2007-03-31

    Serodiagnosis of Rift Valley fever (RVF) currently relies on the use of live or inactivated whole virus as antigens. The recombinant nucleocapsid (N) protein of RVF virus was tested for diagnostic applicability in an indirect enzyme-linked immunosorbent assay (I-ELISA), using sera from experimentally infected sheep (n=128), vaccinated sheep (n=240), and field-collected sera from sheep (n=251), goats (n=362) and cattle (n=100). The N-protein based I-ELISA performed at least as good as VN and HI tests. In goat the diagnostic sensitivity (D-Sn) and specificity (D-Sp) of the I-ELISA was 100% when using the anti-species IgG conjugate. Using protein G as a detection system, the D-Sn and D-Sp in goats were 99.4% and 99.5%, in sheep field sera both 100%, in cattle 100% and 98.3%, respectively. The I-ELISA based on recombinant N-protein has the potential to complement the traditional assays for serodiagnosis of RVF. Advantages of the N-protein are its safety, stability and cost-effectiveness in use and production. PMID:17187944

  15. Evaluation of the Diagnostic Accuracy of a Typhoid IgM Flow Assay for the Diagnosis of Typhoid Fever in Cambodian Children Using a Bayesian Latent Class Model Assuming an Imperfect Gold Standard

    PubMed Central

    Moore, Catrin E.; Pan-Ngum, Wirichada; Wijedoru, Lalith P. M.; Sona, Soeng; Nga, Tran Vu Thieu; Duy, Pham Thanh; Vinh, Phat Voong; Chheng, Kheng; Kumar, Varun; Emary, Kate; Carter, Michael; White, Lisa; Baker, Stephen; Day, Nicholas P. J.; Parry, Christopher M.

    2014-01-01

    Rapid diagnostic tests are needed for typhoid fever (TF) diagnosis in febrile children in endemic areas. Five hundred children admitted to the hospital in Cambodia between 2009 and 2010 with documented fever (≥ 38°C) were investigated using blood cultures (BCs), Salmonella Typhi/Paratyphi A real-time polymerase chain reactions (PCRs), and a Typhoid immunoglobulin M flow assay (IgMFA). Test performance was determined by conventional methods and Bayesian latent class modeling. There were 32 cases of TF (10 BC- and PCR-positive cases, 14 BC-positive and PCR-negative cases, and 8 BC-negative and PCR-positive cases). IgMFA sensitivity was 59.4% (95% confidence interval = 41–76), and specificity was 97.8% (95% confidence interval = 96–99). The model estimate sensitivity for BC was 81.0% (95% credible interval = 54–99). The model estimate sensitivity for PCR was 37.8% (95% credible interval = 26–55), with a specificity of 98.2% (95% credible interval = 97–99). The model estimate sensitivity for IgMFA (≥ 2+) was 77.9% (95% credible interval = 58–90), with a specificity of 97.5% (95% credible interval = 95–100). The model estimates of IgMFA sensitivity and specificity were comparable with BCs and better than estimates using conventional analysis. PMID:24218407

  16. Universal Serial Bus Architecture for Removable Media (USB-ARM)

    Energy Science and Technology Software Center (ESTSC)

    2011-03-09

    USB-ARM creates operating system drivers which sit between removable media and the user and applications. The drivers isolate the media and submit the contents of the media to a virtual machine containing an entire scanning system. This scanning system may include traditional anti-virus, but also allows more detailed analysis of files, including dynamic run-time analysis, helping to prevent “zero-day” threats not already identified in anti-virus signatures. Once cleared, the media is presented to the operatingmore » system, at which point it becomes available to users and applications.« less

  17. Universal Serial Bus Architecture for Removable Media (USB-ARM)

    SciTech Connect

    2011-03-09

    USB-ARM creates operating system drivers which sit between removable media and the user and applications. The drivers isolate the media and submit the contents of the media to a virtual machine containing an entire scanning system. This scanning system may include traditional anti-virus, but also allows more detailed analysis of files, including dynamic run-time analysis, helping to prevent ?zero-day? threats not already identified in anti-virus signatures. Once cleared, the media is presented to the operating system, at which point it becomes available to users and applications.

  18. How Much Security Does Your Library Need?

    ERIC Educational Resources Information Center

    Banerjee, Kyle

    2003-01-01

    Explains how to keep library systems healthy and functioning by taking sensible security measures. Examines why hackers would target library systems and how library systems are compromised. Describes tools that can help, including: firewalls; antivirus software; alarms; network analysis tools; and encryption. Identifies several strategies for

  19. 77 FR 19751 - Privacy Act of 1974, as Amended

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-02

    ... notice was last published in its entirety on April 20, 2010, at 75 FR 20699. The Department subsequently amended the notice on July 2, 2010, at 75 FR 38608, and then again on June 24, 2011, at 76 FR 37193, which... security safeguards; (vii) utilizing antivirus and intrusion detection software; (viii) performing risk...

  20. How To: Protect against a Zero-Hour Attack

    ERIC Educational Resources Information Center

    McCarthy, Rob

    2005-01-01

    In the last year, a series of viruses and worms that caused damage across the Internet in record time has made very clear how vulnerable computer systems are. The MS Blaster, Slammer, Sasser, and Korgo.W worms have shown that signature-based antivirus software and traditional firewalls are not enough to protect networks. Everyone is worried about…

  1. Peace (of Mind) in Our Time

    ERIC Educational Resources Information Center

    Panettieri, Joseph C.

    2007-01-01

    There's no silver bullet to information security; universities must continue to keep their antivirus, anti-spyware, firewall, and patch management systems in good working order. These days, the largest target for hackers appears to be university databases. Now, universities are searching for new solutions to safeguard those systems. This article

  2. How To: Protect against a Zero-Hour Attack

    ERIC Educational Resources Information Center

    McCarthy, Rob

    2005-01-01

    In the last year, a series of viruses and worms that caused damage across the Internet in record time has made very clear how vulnerable computer systems are. The MS Blaster, Slammer, Sasser, and Korgo.W worms have shown that signature-based antivirus software and traditional firewalls are not enough to protect networks. Everyone is worried about

  3. Help for the Help Desk: School District Technology Managers Learn to Do with Less.

    ERIC Educational Resources Information Center

    Kongshem, Lars

    2001-01-01

    Although the E-Rate has been a catalyst for school technology purchases, there are no subsidies for hiring qualified technology support staff. District technology coordinators are relying on technology support systems and shoestring survival strategies, employing standardized equipment and hard-drive configurations, desktop lockdowns, anti-virus

  4. Virus Alert: Ten Steps to Safe Computing.

    ERIC Educational Resources Information Center

    Gunter, Glenda A.

    1997-01-01

    Discusses computer viruses and explains how to detect them; discusses virus protection and the need to update antivirus software; and offers 10 safe computing tips, including scanning floppy disks and commercial software, how to safely download files from the Internet, avoiding pirated software copies, and backing up files. (LRW)

  5. Safe Computing: An Overview of Viruses.

    ERIC Educational Resources Information Center

    Wodarz, Nan

    2001-01-01

    A computer virus is a program that replicates itself, in conjunction with an additional program that can harm a computer system. Common viruses include boot-sector, macro, companion, overwriting, and multipartite. Viruses can be fast, slow, stealthy, and polymorphic. Anti-virus products are described. (MLH)

  6. The Computer Virus Threat and What You Can Do about It.

    ERIC Educational Resources Information Center

    Lateulere, John

    1992-01-01

    Discussion of computer viruses describes two types of viruses and how they work; suggests ways to prevent or minimize virus risk; and explains how to recognize a virus and limit damage once a virus attacks. A sidebar lists several antivirus software products. (two references) (NRP)

  7. Computer Viruses: Pathology and Detection.

    ERIC Educational Resources Information Center

    Maxwell, John R.; Lamon, William E.

    1992-01-01

    Explains how computer viruses were originally created, how a computer can become infected by a virus, how viruses operate, symptoms that indicate a computer is infected, how to detect and remove viruses, and how to prevent a reinfection. A sidebar lists eight antivirus resources. (four references) (LRW)

  8. Science and Technology Resources on the Internet: Computer Security.

    ERIC Educational Resources Information Center

    Kinkus, Jane F.

    2002-01-01

    Discusses issues related to computer security, including confidentiality, integrity, and authentication or availability; and presents a selected list of Web sites that cover the basic issues of computer security under subject headings that include ethics, privacy, kids, antivirus, policies, cryptography, operating system security, and biometrics.

  9. Science and Technology Resources on the Internet: Computer Security.

    ERIC Educational Resources Information Center

    Kinkus, Jane F.

    2002-01-01

    Discusses issues related to computer security, including confidentiality, integrity, and authentication or availability; and presents a selected list of Web sites that cover the basic issues of computer security under subject headings that include ethics, privacy, kids, antivirus, policies, cryptography, operating system security, and biometrics.…

  10. 78 FR 43278 - Publication of Iran General License D

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-19

    ..., chat and email, social networking, sharing of photos and movies, web browsing, and blogging. (2) The....) Anti-virus and anti-malware software designated EAR99 or classified under ECCN 5D992.c, and services necessary for the operation of such software. 7.) Anti-tracking software designated EAR99 or...

  11. Peace (of Mind) in Our Time

    ERIC Educational Resources Information Center

    Panettieri, Joseph C.

    2007-01-01

    There's no silver bullet to information security; universities must continue to keep their antivirus, anti-spyware, firewall, and patch management systems in good working order. These days, the largest target for hackers appears to be university databases. Now, universities are searching for new solutions to safeguard those systems. This article…

  12. Complex-specific immunoglobulin M antibody patterns in humans infected with alphaviruses.

    PubMed

    Calisher, C H; el-Kafrawi, A O; Al-Deen Mahmud, M I; Travassos da Rosa, A P; Bartz, C R; Brummer-Korvenkontio, M; Haksohusodo, S; Suharyono, W

    1986-01-01

    Sera from humans with serologically confirmed eastern equine encephalitis, western equine encephalitis, Pogosta (Ockelbo), Mayaro, Ross River, and chikungunya virus infections were tested by immunoglobulin M (IgM) antibody capture enzyme immunoassay. Diagnostically useful IgM antibody titers were detected, and selected sera with high IgM antibody titers were tested for IgM antibody with nine heterologous alphaviruses. The results provide evidence for the complex specificity of IgM antibody and indicate the usefulness of this test in both individual cases and epidemic situations. PMID:3009526

  13. Distributive immunization of networks against viruses using the `honey-pot' architecture

    NASA Astrophysics Data System (ADS)

    Goldenberg, Jacob; Shavitt, Yuval; Shir, Eran; Solomon, Sorin

    2005-12-01

    Although computer viruses cause tremendous economic loss, defence mechanisms fail to adapt to their rapid evolution. Previous immunization strategies have been characterized as being static and centralized, which has made virus containment difficult or even impossible. We suggest, instead, to propagate the immunization agent as an epidemic. The main problem with epidemic vaccine propagation is that it is bound to lag behind the virus. We suggest giving the vaccine an advantage over the virus by allowing it to leapfrog through a separate, overlapping, partially correlated network. This enables the antivirus to contain the epidemic efficiently. We systemize this concept with a `honey-pot' architecture that achieves both early virus discovery and rapid antivirus dissemination. We present analytic, as well as simulation, results for a set of realistic topologies that illustrate the effectiveness of this approach.

  14. Beyond Firewalls: Professional Certification Ensures Your Staff Will Understand Information Security in Its Proper Context

    ERIC Educational Resources Information Center

    Svetcov, Eric

    2004-01-01

    When it comes to security, many people do not know what they do not know. Consider for example, an administrator who leaves her password taped under her keyboard, or a teacher who doesn't change his password (ever!) or can't be bothered to log out or lock the computer, all the firewalls and antivirus programs in the world will not protect a

  15. An efficient synthesis of novel bis-triazole glycoconjugates via a three-component condensation as a key reaction.

    PubMed

    Cheng, Jie; Gu, Zhenlong; He, Caiyu; Jin, Jie; Wang, Lijun; Li, Guojun; Sun, Bei; Wang, Hui; Bai, Jun

    2015-09-23

    Novel bis-triazole glycoconjugates were designed and prepared successfully via 5 steps from propargyl per-O-acetyl-?-d-glucoside or xyloside (total yield of 48-53%), after utilizing a three-component condensation of propargyl per-O-acetyl-?-d-glycoside, formaldehyde, and sodium azide as a key step to synthesize 2-hydroxymethyl-2H-1,2,3-triazole glycoconjugates. The developed bis-triazole glycoconjugates would be crucial in antivirus pharmacology and chemical biology. PMID:26257377

  16. Toxoplasma gondii-Specific Immunoglobulin M Limits Parasite Dissemination by Preventing Host Cell Invasion

    PubMed Central

    Couper, Kevin N.; Roberts, Craig W.; Brombacher, Frank; Alexander, James; Johnson, Lawrence L.

    2005-01-01

    An important role for immunoglobulin M (IgM) during early acute virulent Toxoplasma gondii infection was identified using IgM?/? mice that lack surface and secretory IgM but maintain normal B-cell functionality and isotype class switching. Following intraperitoneal inoculation with the virulent RH strain, IgM?/? mice displayed significantly fewer peritoneal parasites than wild-type (WT) mice, which correlated with increased tachyzoite dissemination to the liver, lung, and spleen in IgM?/? mice compared with WT mice. Early splenic T-cell activation, as measured by CD69 expression, was augmented in IgM?/? mice, and serum and peritoneal cavity gamma interferon levels were also elevated in IgM?/? mice compared with WT controls. Consequently, the difference in parasite dissemination was not attributable to an impaired proinflammatory immune response in the IgM?/? mice. Specific IgM was found to bind to tachyzoites in vivo in WT mice, and this correlated with an increased ability of antiserum collected from WT mice at day 6 postinfection to block tachyzoite cell invasion, compared with comparable serum collected from IgM?/? mice at the same time point. Tachyzoite invasion of host cells was similar if parasites were incubated with WT or IgM?/? nonimmune serum, suggesting that natural IgM does not function to limit parasite dissemination during early T. gondii infection. Our results highlight an important role for parasite-specific IgM in limiting systemic dissemination of tachyzoites during early acute T. gondii infection. PMID:16299300

  17. An Unusual Case of Bilateral Granulomatous Mastitis

    PubMed Central

    Pistolese, C. A.; Di Trapano, R.; Girardi, V.; Costanzo, E.; Di Poce, I.; Simonetti, G.

    2013-01-01

    Idiopathic granulomatous mastitis (IGM) is an uncommon benign disorder of the breast. At clinical examination, IGM is characterized by an inflammatory process of the breast, usually unilateral. Possible clinical findings are palpable mass with erythematous skin, pain, sterile abscesses, fistula and nipple retraction. Mammography and ultrasound findings are not specific for IGM. Magnetic resonance imaging (MRI) is a useful tool for the differential diagnosis; it is also necessary to delineate the exact extension of the disease and to plan the correct treatment. Final diagnosis is histological. We described an unusual case of IGM with bilateral involvement in a patient with history of pacemaker implantation and IGM typical clinical symptoms. Mammography, ultrasound, and MRI examinations were performed to identify the inflammatory disorder and to plan the correct therapy. Imaging features were correlated with final histological diagnosis of IGM. PMID:23781373

  18. The intergalactic medium and galaxy formation

    NASA Technical Reports Server (NTRS)

    Shapiro, Paul R.

    1989-01-01

    Recent observational and theoretical investigations of the intergalactic medium (IGM), defined as the component of the baryon-electron matter which now occupies the space between galaxies and which filled the pregalactic universe, are reviewed. Topics addressed include the Gunn-Peterson constraint on the history of the IGM, the mean mass density of the IGM at high redshift, requirements for ionizing the IGM, the observed quasar contribution, the thermal and ionization history of the IGM (quasar photoionization, stellar sources of the ionizing background, and alternative sources such as protogalactic shock radiation and the decay of exotic particles), and the hydrodynamical evolution of the IGM. Typical results from observations and numerical simulations are presented graphically.

  19. Goldfish (Carassius auratus L.) possess natural antibodies with trypanocidal activity towards Trypanosoma carassii invitro.

    PubMed

    Katzenback, Barbara A; Plouffe, Debbie A; Belosevic, Miodrag

    2013-05-01

    Natural infection of cyprinids, such as carp, with the extracellular protozoan parasite Trypanosoma carassii can attain up to 100% prevalence and cause significant host morbidity and mortality, particularly in aquaculture settings. Host recovery from T.carassii infection has been shown to be antibody (Immunoglobulin M; IgM)-mediated, conferring long-term immunity in recovered animals upon challenge. To assess the role of IgM in parasite clearance in the goldfish, IgM was purified by PEG-6000 precipitation from goldfish serum collected at 0 (nave), 21 (peak parasitaemia) and 42 (recovery phase; immune) days post infection (dpi) and used for invitro assays. Purified IgM from 0, 21, and 42 dpi serum showed dose- and time-dependent trypanocidal activity invitro. Incubation of T.carassii with 0 dpi IgM showed the greatest reduction in trypanosome numbers after 24h, followed by 42 dpi IgM, and finally by 21 dpi IgM. The trypanocidal activity of the PEG-purified IgM was abrogated by pre-absorption with parasites invitro and was affected by temperature. Furthermore, studies using 0 dpi IgM purified using gel permeation chromatography showed increased trypanocidal activity, with complete elimination of parasites after 12h when incubated with 200?g of 0 dpi IgM, or by 24h when incubated with 80?g or 100?g of 0 dpi IgM. Lastly, invivo passive transfer experiments demonstrated that while immune serum or purified IgM from 42 dpi serum conferred protection against a challenge, neither 0 dpi serum or 0 dpi purified IgM conferred protection against challenge with T.carassii. PMID:23333358

  20. An unusual cause of recurrent pneumonia in adults

    PubMed Central

    Dhir, Varun; Sagar, Vinay; Aggarwal, Ashutosh; Rawat, Amit; Singhal, Manphool

    2014-01-01

    Selective IgM deficiency is a rare primary immunodeficiency defined as isolated low levels of IgM. It presents with recurrent infections and has been described as first presenting in adulthood with recurrent respiratory tract infections. Unlike its better known counterpart of IgA deficiency, this particular immunodeficiency is often overlooked. We present a case of selective IgM deficiency who presented with recurrent respiratory infections. PMID:25125825

  1. Serological cross reactivity to CMV and EBV causes problems in the diagnosis of acute hepatitis E virus infection.

    PubMed

    Hyams, Catherine; Mabayoje, Diana A; Copping, Ruth; Maranao, Desmond; Patel, Mauli; Labbett, Wendy; Haque, Tanzina; Webster, Daniel P

    2014-03-01

    Hepatitis E virus (HEV) infection is an important public health concern as a major cause of enterically-transmitted hepatitis worldwide. The detectable window of viraemia is narrow, and HEV IgM and IgG rise simultaneously in acute infection. Furthermore, previous investigators have shown HEV IgM false positive reactions occur against EBV, CMV and potentially hepatitis A. A retrospective analysis of HEV serology testing was performed at a London tertiary referral hospital over a 3-year period. A thousand four hundred and twenty three serum samples were tested for HEV serology, with 33 samples HEV IgM positive and 28 HEV IgM equivocal. One hundred and eleven samples were HEV IgG positive but IgM negative suggesting past infection. No patients with HEV IgM positivity had false positive reactions against hepatitis A. A high degree of EBV and CMV cross reactivity was noted, with 33.3% and 24.2% of HEV IgM positive samples also testing positive for EBV and CMV IgM, respectively. HEV RNA was detected in four HEV IgM positive samples, indicating true positivity, although three demonstrated cross reactivity against EBV. Only 13.3% of samples with positive HEV IgM were HEV PCR positive, highlighting a low positive predictive value of serology testing. Overall a high level of HEV, EBV and CMV IgM cross reactivity was demonstrated, indicating that serology is unreliable in the diagnosis of acute viral hepatitis. It is concluded that that the diagnosis of viral hepatitis should be based on clinical features, raised transaminases, serology, and confirmatory PCR testing. PMID:24402843

  2. Measurement of the sensitivity of different commercial assays in the diagnosis of CMV infection in pregnancy.

    PubMed

    Gentile, M; Galli, C; Pagnotti, P; Di Marco, P; Tzantzoglou, S; Bellomi, F; Ferreri, M L; Selvaggi, C; Antonelli, G

    2009-08-01

    To evaluate the performance of different commercial assays for the detection of recent cytomegalovirus (CMV) in pregnancy, the sensitivity and specificity of assays for CMV-specific IgM antibodies were compared. Routine specimens from pregnant women were screened for CMV IgM using the Abbott AxSYM assay. Sera that were reactive according to AxSYM were further tested for IgM by other commercial assays. In selected IgM positive samples a CMV IgG avidity assay (Radim) and virus isolation from urine (shell vial) were also performed. The positivity rate for IgM anti-CMV by AxSYM was relatively high (140 out of 492, combining reactive and grayzone results). Only 26 of the 140 samples were positive for IgM according to Radim. The IgG avidity was low in 16 of the 43 samples tested, and the Radim and DiaSorin IgM assays were negative in 5 of them; 2 of the latter cases were also positive for viral isolation according to a shell vial method. There are differences in the sensitivity of the commercially available tests for CMV antibodies. CMV screening in pregnancy is performed as a first step by immunoassays and the choice of highly sensitive IgM test associated with further serological and virological methods could help to identify early primary infections. PMID:19360443

  3. Persistence of immunoglobulin G and immunoglobulin M antibodies after postnatal rubella infection determined by solid-phase radioimmunoassay.

    PubMed Central

    Meurman, O H

    1978-01-01

    The appearance and persistence of immunoglobulin M (IgM) and IgG antibodies in postnatal rubella infections were studied by employing a solid-phase radioimmunoassay test. Altogether, 222 serial serum specimens from 51 patients with acute rubella infection were tested. Both IgG and IgM antibodies developed rapidly and appeared in all patients within 4 days after the onset of rash. In some patients, the IgM antibodies clearly preceded the IgG antibodies; however, the reverse situation was also noticed in a few cases. The IgG antibodies showed only minor changes after 8 to 10 days from the onset of rash. The IgM titers also reached a maximum level at approximately 8 to 10 days after the onset of rash, after which time a rapid decrease was normally seen. The mean half-life of IgM antibodies after 15 days from the onset of rash was 4.5 days, giving for IgM antibodies persistence times from 43 to approximately 80 days. Two patients with a prolonged IgM antibody response were detected. One of these patients had bilateral arthritis of the knee as a complication, whereas in the other patient no complication caused by rubella virus was detected. The IgM antibody response and its value in diagnosis are discussed. PMID:624770

  4. Interaction of temperature and salinity on the expression of immunity factors in different tissues of juvenile turbot Scophthalmus maximus based on response surface methodology

    NASA Astrophysics Data System (ADS)

    Huang, Zhihui; Ma, Aijun; Wang, Xin'an; Lei, Jilin; Li, Weiye; Wang, Ting; Yang, Zhi; Qu, Jiangbo

    2015-01-01

    Central Composite Design (CCD) and response surface methodology were used in the experiment to examine the combined effect of temperature (16-28C) and salinity (18-42) on Hsp70 and IgM genes expression levels in turbot ( Scophthalmus maximus) liver and kidney. The results showed that the coefficients of determination ( R 2 =0.965 2 for liver Hsp70, 0.972 9 for kidney Hsp70, 0.921 for liver IgM and 0.962 1 for kidney IgM) and probability values ( P<0.01) were significant for the regression model. The interactive effect between temperature and salinity on liver Hsp70, kidney Hsp70 and liver IgM were not significant ( P>0.05), while the interactive effect between temperature and salinity on kidney IgM was significant ( P<0.01). The model equation could be used in practice for forecasting Hsp70 and IgM genes expression levels in the liver and kidney of juvenile turbot via applying statistical optimization of the response of interest, at which the maximum liver Hsp70, kidney Hsp70, liver IgM and kidney IgM of 1.48, 1.49, 2.48, and 1.38, respectively, were reached. The present model may be valuable in assessing the feasibility of turbot farming at different geographic locations and, furthermore, could be a useful reference for scientists studying the immunity of turbot.

  5. Identification and characterization of two distinct bursal B-cell subpopulations following infectious bursal disease virus infection of White Leghorn chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Infectious bursal disease virus (IBDV) is an immunosuppressive virus which primarily infects IgM, B-cells in the bursa of Fabricius. Flow cytometric analysis was used to phenotype B-cell populations in the bursa and spleen following IBDV infection. In the bursa, two IgM B-cell subpopulations, desig...

  6. Effects of a hot intergalactic medium

    NASA Technical Reports Server (NTRS)

    Taylor, Gregory B.; Wright, Edward L.

    1989-01-01

    One effect a hot intergalactic medium (IGM) would have would be to produce an isotropic X-ray background through thermal bremsstrahlung. Such a background was modeled including both relativistic electron-ion and electron-electron emission; the observed X-ray measurements could be fit with a current temperature of 10.2 keV and Omega (IGM) of 0.27, assuming that the IGM was instantaneously heated at a redshift of 5 and cools by relativistic adiabatic expansion and Compton cooling. Such a hot IGM would also distort the cosmic microwave background spectrum by inverse Compton scattering off relativistic electrons. This distortion was modeled using the relativistic treatment. When including the recent data of Matsumoto et al., an undistorted radiation temperature of 2.86 K and an Omega (IGM) of 0.41 was found.

  7. Chlamydophila pneumoniae diagnostics: importance of methodology in relation to timing of sampling.

    PubMed

    Hvidsten, D; Halvorsen, D S; Berdal, B P; Gutteberg, T J

    2009-01-01

    The diagnostic impact of PCR-based detection was compared to single-serum IgM antibody measurement and IgG antibody seroconversion during an outbreak of Chlamydophila pneumoniae in a military community. Nasopharyngeal swabs for PCR-based detection, and serum, were obtained from 127 conscripts during the outbreak. Serum, drawn many months before the outbreak, provided the baseline antibody status. C. pneumoniae IgM and IgG antibodies were assayed using microimmunofluorescence (MIF), enzyme immunoassay (EIA) and recombinant ELISA (rELISA). Two reference standard tests were applied: (i) C. pneumoniae PCR; and (ii) assay of C. pneumoniae IgM antibodies, defined as positive if >or=2 IgM antibody assays (i.e. rELISA with MIF and/or EIA) were positive. In 33 subjects, of whom two tested negative according to IgM antibody assays and IgG seroconversion, C. pneumoniae DNA was detected by PCR. The sensitivities were 79%, 85%, 88% and 68%, respectively, and the specificities were 86%, 84%, 78% and 93%, respectively, for MIF IgM, EIA IgM, rELISA IgM and PCR. In two subjects, acute infection was diagnosed on the basis of IgG antibody seroconversion alone. The sensitivity of PCR detection was lower than that of any IgM antibody assay. This may be explained by the late sampling, or clearance of the organism following antibiotic treatment. The results of assay evaluation studies are affected not only by the choice of reference standard tests, but also by the timing of sampling for the different test principles used. On the basis of these findings, a combination of nasopharyngeal swabbing for PCR detection and specific single-serum IgM measurement is recommended in cases of acute respiratory C. pneumoniae infection. PMID:19046171

  8. Stability and Hopf bifurcation for a delayed SLBRS computer virus model.

    PubMed

    Zhang, Zizhen; Yang, Huizhong

    2014-01-01

    By incorporating the time delay due to the period that computers use antivirus software to clean the virus into the SLBRS model a delayed SLBRS computer virus model is proposed in this paper. The dynamical behaviors which include local stability and Hopf bifurcation are investigated by regarding the delay as bifurcating parameter. Specially, direction and stability of the Hopf bifurcation are derived by applying the normal form method and center manifold theory. Finally, an illustrative example is also presented to testify our analytical results. PMID:25202722

  9. Iridoid and bis-iridoid glucosides from the fruit of Gardenia jasminoides.

    PubMed

    Li, Hai-Bo; Yu, Yang; Wang, Zhen-Zhong; Dai, Yi; Gao, Hao; Xiao, Wei; Yao, Xin-Sheng

    2013-07-01

    Three new iridoid glucosides, 6?-O-trans-feruloylgenipin gentiobioside (1), 2'-O-trans-caffeoylgardoside (2), jasmigeniposide A (3), and one new bis-iridoid glucoside, jasmigeniposide B (4), along with six known analogues (5-10), were isolated from the fruit of Gardenia jasminoides. Their structures were established on the basis of spectroscopic analyses and chemical methods. Anti-virus activity of isolated compounds were evaluated in vitro and only compound 9 showed moderate inhibitory activity against H1N1 with 50% effective concentration (EC50) value of 104.36 ?M, and selective index (SI) value greater than 4.79. PMID:23567862

  10. Stability and Hopf Bifurcation for a Delayed SLBRS Computer Virus Model

    PubMed Central

    Yang, Huizhong

    2014-01-01

    By incorporating the time delay due to the period that computers use antivirus software to clean the virus into the SLBRS model a delayed SLBRS computer virus model is proposed in this paper. The dynamical behaviors which include local stability and Hopf bifurcation are investigated by regarding the delay as bifurcating parameter. Specially, direction and stability of the Hopf bifurcation are derived by applying the normal form method and center manifold theory. Finally, an illustrative example is also presented to testify our analytical results. PMID:25202722

  11. Small-angle neutron scattering study of recombinant yeast-derived human hepatitis B virus surface antigen vaccine particle

    NASA Astrophysics Data System (ADS)

    Sato, M.; Ito, Y.; Kameyama, K.; Imai, M.; Ishikawa, N.; Takagi, T.

    1995-02-01

    The overall and internal structure of recombinant yeast-derived human hepatitis B virus surface antigen vaccine particles was investigated by small-angle neutron scattering using the contrast variation method. The vaccine is a nearly spherical particle, and its contrast-matching point was determined to be at about 24% D 2O content, indicating that a large part of the vaccine particle is occupied by lipids and carbohydrates from the yeast. The Stuhrmann plot suggests that the surface antigens exist predominantly in the peripheral region of the particle, which is favorable to the induction of anti-virus antibodies.

  12. Identification of Malicious Web Pages by Inductive Learning

    NASA Astrophysics Data System (ADS)

    Liu, Peishun; Wang, Xuefang

    Malicious web pages are an increasing threat to current computer systems in recent years. Traditional anti-virus techniques focus typically on detection of the static signatures of Malware and are ineffective against these new threats because they cannot deal with zero-day attacks. In this paper, a novel classification method for detecting malicious web pages is presented. This method is generalization and specialization of attack pattern based on inductive learning, which can be used for updating and expanding knowledge database. The attack pattern is established from an example and generalized by inductive learning, which can be used to detect unknown attacks whose behavior is similar to the example.

  13. [Advances in research of chemical constituents and pharmacological activites of Ephedra].

    PubMed

    Ding, Li-Li; Shi, Song-Shan; Cui, Jian; Wang, Shun-Chun; Wang, Zheng-Tao

    2006-10-01

    The collected information is an attempt to cover the more recent developments in the phytochemistry and pharmacology of this genus. During the past years, alkaloids, flavonoids, volatile oils, organic acids, polysaccharides, tannins and phenolic constituents have been isolated from Ephedra. Pharmacological studies are described according to hypoglycemic effects, anticoagulated blood properties, depressurization, immunosuppressive activity, antioxidation and antivirus activity and so on. The information summarized here is intended to provid a rational foundation for the futher development and utilization of Ephedra which is rich in China. PMID:17225527

  14. Evaluation of Tools for Protection of Interest against Hacking and Cracking

    NASA Astrophysics Data System (ADS)

    Jahankhani, Hossein; Antonijevic, Branko; Walcott, Terry

    The internet considered a tool that effectively ensures communication globally has been hindered by hackers and crackers continuously. In so doing, a multitude of network facilitated tools such as firewalls, virtual private networks (VPN) and a variety of antivirus software packages has been enabled for dealing with such predicaments. However, more often than not these facilitated tools are marketed as perfect solutions to the ever culminating problems such as loss of data and privacy in networked and world wide intercommunications. We provide a forum for addressing these perceived problems in this paper.

  15. Malware distributed collection and pre-classification system using honeypot technology

    NASA Astrophysics Data System (ADS)

    Grgio, Andr R. A.; Oliveira, Isabela L.; Santos, Rafael D. C.; Cansian, Adriano M.; de Geus, Paulo L.

    2009-04-01

    Malware has become a major threat in the last years due to the ease of spread through the Internet. Malware detection has become difficult with the use of compression, polymorphic methods and techniques to detect and disable security software. Those and other obfuscation techniques pose a problem for detection and classification schemes that analyze malware behavior. In this paper we propose a distributed architecture to improve malware collection using different honeypot technologies to increase the variety of malware collected. We also present a daemon tool developed to grab malware distributed through spam and a pre-classification technique that uses antivirus technology to separate malware in generic classes.

  16. Acute Liver Injury Is Independent of B Cells or Immunoglobulin M

    PubMed Central

    Richards, James A.; Bucsaiova, Martina; Hesketh, Emily E.; Ventre, Chiara; Henderson, Neil C.; Simpson, Kenneth; Bellamy, Christopher O. C.; Howie, Sarah E. M.; Anderton, Stephen M.; Hughes, Jeremy; Wigmore, Stephen J.

    2015-01-01

    Background & Aims Acute liver injury is a clinically important pathology and results in the release of Danger Associated Molecular Patterns, which initiate an immune response. Withdrawal of the injurious agent and curtailing any pathogenic secondary immune response may allow spontaneous resolution of injury. The role B cells and Immunoglobulin M (IgM) play in acute liver injury is largely unknown and it was proposed that B cells and/or IgM would play a significant role in its pathogenesis. Methods Tissue from 3 models of experimental liver injury (ischemia-reperfusion injury, concanavalin A hepatitis and paracetamol-induced liver injury) and patients transplanted following paracetamol overdose were stained for evidence of IgM deposition. Mice deficient in B cells (and IgM) were used to dissect out the role B cells and/or IgM played in the development or resolution of injury. Serum transfer into mice lacking IgM was used to establish the role IgM plays in injury. Results Significant deposition of IgM was seen in the explanted livers of patients transplanted following paracetamol overdose as well as in 3 experimental models of acute liver injury (ischemia-reperfusion injury, concanavalin A hepatitis and paracetamol-induced liver injury). Serum transfer into IgM-deficient mice failed to reconstitute injury (p = 0.66), despite successful engraftment of IgM. Mice deficient in both T and B cells (RAG1-/-) mice (p<0.001), but not B cell deficient (μMT) mice (p = 0.93), were significantly protected from injury. Further interrogation with T cell deficient (CD3εKO) mice confirmed that the T cell component is a key mediator of sterile liver injury. Mice deficient in B cells and IgM mice did not have a significant delay in resolution following acute liver injury. Discussion IgM deposition appears to be common feature of both human and murine sterile liver injury. However, neither IgM nor B cells, play a significant role in the development of or resolution from acute liver injury. T cells appear to be key mediators of injury. In conclusion, the therapeutic targeting of IgM or B cells (e.g. with Rituximab) would have limited benefit in protecting patients from acute liver injury. PMID:26406765

  17. Numerical study of the properties of optical vortex array laser tweezers.

    PubMed

    Kuo, Chun-Fu; Chu, Shu-Chun

    2013-11-01

    Chu et al. constructed a kind of Ince-Gaussian modes (IGM)-based vortex array laser beams consisting of p x p embedded optical vortexes from Ince-Gaussian modes, IG(e)(p,p) modes [Opt. Express 16, 19934 (2008)]. Such an IGM-based vortex array laser beams maintains its vortex array profile during both propagation and focusing, and is applicable to optical tweezers. This study uses the discrete dipole approximation (DDA) method to study the properties of the IGM-based vortex array laser tweezers while it traps dielectric particles. This study calculates the resultant force exerted on the spherical dielectric particles of different sizes situated at the IGM-based vortex array laser beam waist. Numerical results show that the number of trapping spots of a structure light (i.e. IGM-based vortex laser beam), is depended on the relation between the trapped particle size and the structure light beam size. While the trapped particle is small comparing to the beam size of the IGM-based vortex array laser beams, the IGM-based vortex array laser beams tweezers are suitable for multiple traps. Conversely, the tweezers is suitable for single traps. The results of this study is useful to the future development of the vortex array laser tweezers applications. PMID:24216863

  18. Abrogation of lupus nephritis in Activation-Induced Deaminase-deficient MRL/lpr Mice1

    PubMed Central

    Jiang, Chuancang; Foley, Julie; Clayton, Natasha; Kissling, Grace; Jokinen, Micheal; Herbert, Ronald; Diaz, Marilyn

    2007-01-01

    We generated MRL/lpr mice deficient in the Activation Induced Deaminase (AID). Because AID is required for immunoglobulin hypermutation and class switch recombination, these mice lack hypermutated IgG antibodies. Unlike their AID wild-type littermates, AID-deficient MRL/lpr mice not only lacked autoreactive IgG antibodies, but also experienced a dramatic increase in the levels of autoreactive IgM. This phenotype in AID-deficient mice translated into a dramatic reduction in glomerulonephritis, minimal mononuclear cell infiltration in the kidney, and a dramatic increase in survival to levels comparable to previously reported for MRL/lpr mice completely lacking B cells and levels well below those of mice lacking secreted antibodies. Therefore, this study, wherein littermates with either high levels of autoreactive IgM or autorective IgG are directly examined, proves that autoreactive IgM antibodies alone are not sufficient to promote kidney disease in MRL/lpr mice. In addition, the substantial decrease in mortality combined with a dramatic increase in autoreactive IgM antibodies in AID-deficient MRL/lpr mice, suggest that autoreactive IgM antibodies might not only fail to promote nephritis, but may also provide a protective role in MRL/lpr mice. This novel mouse model containing high levels of autoreactive, unmutated IgM antibodies will help delineate the contribution of autoreactive IgM to autoimmunity. PMID:17513793

  19. Study of two different enzyme immunoassays for the detection of Mayaro virus antibodies.

    PubMed

    Figueiredo, L T; Nogueira, R M; Cavalcanti, S M; Schatzmayr, H; da Rosa, A T

    1989-01-01

    This paper presents the evaluation of an enzyme immunoassay in which Mayaro virus-infected cultured cells are used as antigen (EIA-ICC) and an IgM antibody capture ELISA (MAC-ELISA) for Mayaro serologic diagnosis using 114 human sera obtained during a Mayaro outbreak occurred in Bolivia, in 1987. Results were compared with those obtained by haemagglutination-inhibition test (HAI). MAC-ELISA was the most sensitive technique for anti-Mayaro IgM detection. MAC-ELISA was twice as sensitive as IgM EIA-ICC. The data shows that MAC-ELISA is a practical and valid technique for diagnosis of recent Mayaro infection. IgG EIA-ICC showed high sensitivity and high specificity compared to HAI. The combination of anti-Mayaro IgG and IgM EIA-ICC results presented the highest sensitivity of the study. Anti-Mayaro IgG and IgM simultaneous detection by EIA-ICC can be used for recent infection diagnosis (in spite of a less sensitive IgM detection than by MAC-ELISA), for surveillance and sero-epidemiologic studies, and for studies of IgG and IgM responses to Mayaro infection. PMID:2562487

  20. Chikungunya and dengue virus infections during pregnancy: seroprevalence, seroincidence and maternal-fetal transmission, southern Thailand, 2009-2010.

    PubMed

    Laoprasopwattana, K; Suntharasaj, T; Petmanee, P; Suddeaugrai, O; Geater, A

    2016-01-01

    Limited information is available on the seroprevalence of chikungunya virus (CHIKV) infection and maternal-fetal transmission incidence of CHIKV and dengue virus (DENV) infections during the 2008-2009 CHIKV outbreak in southern Thailand. A community-based post-epidemic seroprevalence study was conducted in parturient women admitted to the Thepa District Hospital in Songkhla Province, Thailand, for delivery from November 2009 to May 2010. The women were tested for chikungunya (CHIK) IgM/IgG and dengue (DEN) IgM/IgG. Cord blood samples were also tested for CHIK IgM or DEN IgM in women who tested positive for CHIK IgM or DEN IgM, respectively. The seroprevalence of CHIKV infection (CHIK IgM or IgG positive) was 227/319 (71·2%) with pre-outbreak seroprevalence (IgM-/IgG+) of 43·6% and the seroprevalence of DENV infection was 288/319 (90·3%). Complications during pregnancy, newborn outcomes and congenital anomalies were not different in those who had recent, remote or no CHIKV infections. None of the newborns whose mothers were CHIK or DEN IgM positive had cord blood positive for both CHIK and DEN IgM. In conclusion, both CHIKV and DENV are endemic in southern Thailand; during the recent CHIKV outbreak CHIK seroprevalence increased from 43·6% to 71·2%. PMID:26113247

  1. Influence of the mu-chain C-terminal sequence on polymerization of immunoglobulin M.

    PubMed

    Getahun, A; Lundqvist, M; Middleton, D; Warr, G; Pilstrm, L

    1999-07-01

    Immunoglobulin (IgM) is found in various states of covalent polymerization (microL)n, where n is typically 8, 10, or 12. The usual form of IgM of bony fish is tetrameric (8 microL units) as compared to the pentameric form (10 microL units) observed in cartilaginous fish and mammals. Two hypotheses were tested in this study. First, that the length of the mu-chain C terminus following Cys575 determines whether an IgM polymerizes as a tetramer or as a pentamer. This was tested by examining the covalent polymerization state of mouse IgM mutated to contain a series of mu-chain C-termini from bony and cartilaginous fish. The results proved this hypothesis wrong: mouse IgM bearing the C-terminal sequence of shark, salmon and cod mu-chain behaved identically to native mouse IgM, forming predominantly (microL)10 and (microL)12 forms. The second hypothesis was that an additional Cys residue near the C terminus of the mu-chain is responsible for the multiple covalent structures seen in IgM of the channel catfish. The addition of a catfish C terminus to the mouse mu-chain resulted, as predicted, in the production of a series of covalently bonded forms, with the major species being (microL)4. When a Ser-Cys unit was removed from the catfish C terminus added to the mouse mu-chain, this resulted in production of IgM indistinguishable in structure from that of wild-type mouse IgM. PMID:10447761

  2. Evidence that intestinal IgA plasma cells in mu, kappa transgenic mice are derived from B-1 (Ly-1 B) cells.

    PubMed

    Kroese, F G; Ammerlaan, W A; Kantor, A B

    1993-10-01

    B6-Sp6 transgenic mice carry fully rearranged (BALB/c-derived, Igh-Ca allotype) mu heavy chain and kappa light chain transgenes, specific for trinitrophenyl, on a C57BL background (Igh-Cb allotype). FACS analyses show that the majority of B cells in peripheral lymphoid organs and bone marrow (BM) express transgenic IgM exclusively. A small proportion of the B cells, however, express endogenous IgM, usually concomitant with transgenic IgM. Three criteria establish that the endogenous IgM expressing B cells belong to the B-1 cell lineage. (i) Endogenous IgM expressing B cells in B6-Sp6 mice have the same localization pattern as B-1 cells from normal animals: they are enriched in the peritoneal cavity. (ii) The endogenous IgM+ B cells have the phenotype of B-1 cells: the endogenous IgM+ peritoneal B cells express Mac-1 (CD11b) and low levels of IgD, and most also express CD5 (Ly-1). (iii) B6-Sp6 BM poorly reconstitutes endogenous IgM+ B cells, just as adult BM from normal mice poorly reconstitutes B-1 cells. In contrast, B cells which only express the transgene are readily reconstituted by B6-Sp6 BM. The few endogenous IgM+ cells in the B6-Sp6 BM recipients are located in the peritoneal cavity and have the phenotype of B-1b cells (previously the Ly-1 B sister population), which are known to be reconstituted by adult BM. Two-color immunofluorescence staining of tissue sections from the gut and from isolated gut lamina propria cells shows the presence of many IgA containing cells, about one-third of which simultaneously express cytoplasmic (transgenic) IgM. The C-region of this IgA is produced by endogenous C alpha genes, because the transgene encodes only for C mu. Furthermore, the majority of gut IgA containing cells do not express the idiotype of the transgene, indicating that most of the gut IgA cells are encoded by endogenous VH genes and thus the result of an isotype switch from endogenous IgM expressing B cells. Since the endogenous IgM+ cells are B-1 cells (both B-1a and B-1b), the data strongly indicate that the intestinal IgA plasma cells also belong to the B-1 cell lineage. PMID:7505612

  3. Serum immunoglobulin levels in healthy adults of various ethnic groups in a rural family practice in Israel.

    PubMed

    Yodfat, Y; Keren, L; Zlotnick, A

    1975-12-01

    A study on the immunoglobulin levels of five ethnic groups in a rural population in Israel was carried out. The ethnic group comprised Yemenite, Cochin, Kurd, North African, and Ashkenazi Jews. Yemenites have a low level of IgA, Ashkenazis have a high IgM level, Cochins and North Africans have high levels of IgG and IgA, and Kurds show low IgM levels. Females have higher IgM levels than males. No positive correlation between immunoglobulin levels and age could be demonstrated. A connection between these levels and exogenous and endogenous factors in the various ethnic groups is discussed. PMID:1230499

  4. Plasma effects on extragalactic ultra-high-energy cosmic ray hadron beams in cosmic voids

    SciTech Connect

    Krakau, S.; Schlickeiser, R. E-mail: rsch@tp4.rub.de

    2014-07-01

    The linear instability of an ultrarelativistic hadron beam (Γ {sub b} ≈ 10{sup 6}) in the unmagnetized intergalactic medium (IGM) is investigated with respect to the excitation of collective electrostatic and aperiodic electromagnetic fluctuations. This analysis is important for the propagation of extragalactic ultrarelativistic cosmic rays (E > 10{sup 15} eV) from their distant sources to Earth. We calculate minimum instability growth times that are orders of magnitude shorter than the cosmic ray propagation time in the IGM. Due to nonlinear effects, especially the modulation instability, the cosmic ray beam stabilizes and can propagate with nearly no energy loss through the IGM.

  5. Conjunctival Flap Covering Combined with Antiviral and Steroid Therapy for Severe Herpes Simplex Virus Necrotizing Stromal Keratitis

    PubMed Central

    Jia, Yanni; Li, Suxia; Wang, Ting; Tan, Yaohong; Shi, Weiyun

    2015-01-01

    Herpes simplex virus (HSV) necrotizing stromal keratitis is a common type of herpetic stromal keratitis (HSK). Antiviral medication alone cannot control the disease, and corticosteroid eye drops may aggravate the ulcer and result in corneal perforation. Amniotic membrane transplantation effectively treats superficial corneal ulcer resulting from necrotizing stromal HSK. However, the efficacy of this approach seems to be limited for more serious cases. This study presented the clinical treatment of severe HSV necrotizing stromal keratitis (ulcer depth greater than half of the corneal stroma) by conjunctival flap covering surgery in 25 patients (25 eyes) combined with antivirus and corticosteroid treatment at Shandong Eye Hospital from January 2007 to December 2013. Clinical results showed that the mean best spectacle-corrected visual acuity improved from preoperative 20/333 to postoperative 20/40 (P < 0.05). All patients recovered ocular surface stabilization. There was recurrence in two eyes, which was cured with antiviral medication. Conjunctival flap covering combined with antivirus and corticosteroid treatment is effective in treating severe HSV necrotizing stromal keratitis. PMID:25785282

  6. Cytokine profiles in multifocal motor neuropathy and progressive muscular atrophy.

    PubMed

    Vlam, L; Stam, M; de Jager, W; Cats, E A; van den Berg, L H; van der Pol, W L

    2015-09-15

    Multifocal motor neuropathy (MMN) and progressive muscular atrophy (PMA) are associated with IgM monoclonal gammopathy or the presence IgM anti-GM1-antibodies. To further investigate the pathophysiology of MMN and PMA we determined concentrations of 16 mainly B-cell associated inflammatory markers in serum from 25 patients with MMN, 55 patients with PMA, 25 patients with amyotrophic lateral sclerosis (ALS) and 50 healthy controls. Median serum concentrations of the 16 tested cytokines and chemokines were not significantly increased in patients with MMN or patients with PMA, irrespective of the presence of IgM monoclonal gammopathy or high IgM anti-GM1 antibodies. These results argue against a systemic B-cell mediated immune response underlying the pathogenesis of MMN and PMA. PMID:26298317

  7. Hepatitis B Test

    MedlinePLUS

    ... IgM; anti-HBe; Hepatitis B e Antibody; HBV DNA Formal name: Hepatitis B Virus Testing Related tests: ... produced by the virus, and others detect viral DNA . The main uses for HBV tests include: To ...

  8. [Relationships between the content of circulating immune complexes, the concentration of serum immunoglobulins and the titers of specific antibodies in patients with tick-borne encephalitis].

    PubMed

    Ivanov, V G; Ivanov, G G; Barsukov, A K; Kuznetsova, A I

    2004-01-01

    In the blood serum of tick-borne encephalitis (TBE) patients the detection rate and concentration of circulating immune complexes, as well as the content of serum IgA, IgM and IgG, were evaluated. The formation of immune complexes was found to depend on IgM and IgG specific antibodies to TBE virus, the period of the disease and the clinical form of virus infection. PMID:15346962

  9. Modulation of the IL-6 Receptor α Underlies GLI2-Mediated Regulation of Ig Secretion in Waldenström Macroglobulinemia Cells.

    PubMed

    Jackson, David A; Smith, Timothy D; Amarsaikhan, Nansalmaa; Han, Weiguo; Neil, Matthew S; Boi, Shannon K; Vrabel, Anne M; Tolosa, Ezequiel J; Almada, Luciana L; Fernandez-Zapico, Martin E; Elsawa, Sherine F

    2015-09-15

    Ig secretion by terminally differentiated B cells is an important component of the immune response to foreign pathogens. Its overproduction is a defining characteristic of several B cell malignancies, including Waldenström macroglobulinemia (WM), where elevated IgM is associated with significant morbidity and poor prognosis. Therefore, the identification and characterization of the mechanisms controlling Ig secretion are of great importance for the development of future therapeutic approaches for this disease. In this study, we define a novel pathway involving the oncogenic transcription factor GLI2 modulating IgM secretion by WM malignant cells. Pharmacological and genetic inhibition of GLI2 in WM malignant cells resulted in a reduction in IgM secretion. Screening for a mechanism identified the IL-6Rα (gp80) subunit as a downstream target of GLI2 mediating the regulation of IgM secretion. Using a combination of expression, luciferase, and chromatin immunoprecipitation assays we demonstrate that GLI2 binds to the IL-6Rα promoter and regulates its activity as well as the expression of this receptor. Additionally, we were able to rescue the reduction in IgM secretion in the GLI2 knockdown group by overexpressing IL-6Rα, thus defining the functional significance of this receptor in GLI2-mediated regulation of IgM secretion. Interestingly, this occurred independent of Hedgehog signaling, a known regulator of GLI2, as manipulation of Hedgehog had no effect on IgM secretion. Given the poor prognosis associated with elevated IgM in WM patients, components of this new signaling axis could be important therapeutic targets. PMID:26238488

  10. TEMPORAL SMEARING OF TRANSIENT RADIO SOURCES BY THE INTERGALACTIC MEDIUM

    SciTech Connect

    Macquart, Jean-Pierre; Koay, Jun Yi

    2013-10-20

    The temporal smearing of impulsive radio events at cosmological redshifts probes the properties of the ionized intergalactic medium (IGM). We relate the degree of temporal smearing and the profile of a scattered source to the evolution of a turbulent structure in the IGM as a function of redshift. We estimate the degree of scattering expected by analyzing the contributions to the scattering measure of the various components of baryonic matter embedded in the IGM, including the diffuse IGM, intervening galaxies, and intracluster gas. These estimates predict that the amount of temporal smearing expected at 300 MHz is typically as low as ?1 ms and suggests that these bursts may be detectable with low-frequency widefield arrays. A generalization of the dispersion-measure-scattering-measure relation observed for Galactic scattering to the densities and turbulent conditions relevant to the IGM suggests that scattering measures on the order of 10{sup 6} kpc m{sup 20/3} would be expected at z ? 1. This scattering is sufficiently low enough that its effects would not, for most lines of sight, be manifested in existing observations of the scatter broadening in images of extragalactic compact sources. The redshift dependence on the temporal smearing discriminates between scattering that occurs in the host galaxy of the burst and the IGM, with ?{sub host}?(1 + z){sup 3} if the scattering probes length scales below the inner scale of the turbulence or ?{sub host}?(1 + z){sup 17/5} if the turbulence follows a Kolmogorov spectrum. This differs strongly from the expected IGM scaling ?{sub IGM} ? z {sup 2} for z ?< 1 and (1 + z){sup 0.20.5} for z ?> 1.

  11. Rapid diagnosis of acute mumps infection by a direct immunoglobulin M antibody capture enzyme immunoassay with labeled antigen.

    PubMed Central

    Gut, J P; Spiess, C; Schmitt, S; Kirn, A

    1985-01-01

    A new immunoglobulin M (IgM) antibody capture enzyme immunoassay with peroxidase-labeled mumps antigen (dMACEIA) is described, and its suitability for practical diagnosis of acute mumps infection is evaluated. All 54 patients with proven mumps infection that were tested showed mumps-specific IgM antibodies. On the other hand, no specific IgM antibodies were present in 16 cases of suspected mumps that could not be confirmed by classical complement fixation serology, and IgM mumps virus antibodies could be detected neither in the sera of 100 healthy individuals nor in those of 16 patients positive for rheumatoid factor. In all, 22 children with acute respiratory illness caused by parainfluenza virus and 44 patients with infections due to other viruses showed no IgM response in mumps dMACEIA. The particular characteristic in which complement fixation antibodies against mumps nucleocapsids appear before and disappear earlier than antibodies to the enveloped mumps virus could not be demonstrated in the dMACEIA. In an extensive epidemic of mumps virus infection, the dMACEIA gave a clear diagnosis of mumps infection in 200 out of 371 suspected cases. By day 2 of the illness, 71% of the patients had detectable IgM, and by day 3, all of them had detectable IgM. In 99% of the cases, dMACEIA gave a positive result in the first available serum specimens, most of which were negative for complement fixation antibodies. A positive but only moderate correlation was thus observed between the two serological procedures. IgM antibodies persisted for at least 6 weeks. The dMACEIA, performed in 3 h, offers a reliable, simple, and rapid alternative to routine methods for detection of acute mumps infection. PMID:3884652

  12. Analysis of complement fixation and commercial enzyme immunoassays for detection of antibodies to Mycoplasma pneumoniae in human serum.

    PubMed

    Thacker, W L; Talkington, D F

    2000-09-01

    The Meridian ImmunoCard (IC), GenBio ImmunoWELL-IgM, and Remel EIA commercial antibody tests are qualitative enzyme immunoassays that detect antibodies to Mycoplasma pneumoniae in serum. These tests were compared to an M. pneumoniae complement fixation (CF) assay, which uses a commercially available antigen component. The Meridian IC and the ImmunoWELL-IgM detect immunoglobulin M (IgM) only; the Remel EIA and the CF test detect both IgM and IgG antibodies. Detection of specific IgM antibody, which appears early in infection, can be, but is not always, indicative of a recent or current infection. Paired serum samples from 64 adult patients with probable M. pneumoniae infection were examined with each of the four tests. Thirty (47%) of the 64 acute-phase sera were IgM positive by Meridian IC, 26 (41%) were positive by Remel EIA, 24 (38%) were positive by CF, and 15 (23%) were positive by ImmunoWELL-IgM. When both the acute- and convalescent-phase serum samples from each patient were examined, 61 (95%) of the 64 patients were positive by CF, 60 patients (94%) were positive by Remel EIA, 52 patients (81%) were IgM positive by the Meridian IC, and 29 patients (45%) were IgM positive by the ImmunoWELL-IgM assay. The Meridian IC was more sensitive than the other tests for early detection of IgM antibodies. However, after examining paired serum samples, we concluded that the detection of IgM alone may not be useful for all cases of mycoplasma infection, especially in an adult population. PMID:10973454

  13. How to Determine the Accuracy of an Alternative Diagnostic Test when It Is Actually Better than the Reference Tests: A Re-Evaluation of Diagnostic Tests for Scrub Typhus Using Bayesian LCMs

    PubMed Central

    Lim, Cherry; Paris, Daniel H.; Blacksell, Stuart D.; Laongnualpanich, Achara; Kantipong, Pacharee; Chierakul, Wirongrong; Wuthiekanun, Vanaporn; Day, Nicholas P. J.; Cooper, Ben S.; Limmathurotsakul, Direk

    2015-01-01

    Background The indirect immunofluorescence assay (IFA) is considered a reference test for scrub typhus. Recently, the Scrub Typhus Infection Criteria (STIC; a combination of culture, PCR assays and IFA IgM) were proposed as a reference standard for evaluating alternative diagnostic tests. Here, we use Bayesian latent class models (LCMs) to estimate the true accuracy of each diagnostic test, and of STIC, for diagnosing scrub typhus. Methods/Principal Findings Data from 161 patients with undifferentiated fever were re-evaluated using Bayesian LCMs. Every patient was evaluated for the presence of an eschar, and tested with blood culture for Orientia tsutsugamushi, three different PCR assays, IFA IgM, and the Panbio IgM immunochromatographic test (ICT). True sensitivity and specificity of culture (24.4% and 100%), 56kDa PCR assay (56.8% and 98.4%), 47kDa PCR assay (63.2% and 96.1%), groEL PCR assay (71.4% and 93.0%), IFA IgM (70.0% and 83.8%), PanBio IgM ICT (72.8% and 96.8%), presence of eschar (42.7% and 98.9%) and STIC (90.5% and 82.5%) estimated by Bayesian LCM were considerably different from those obtained when using STIC as a reference standard. The IgM ICT had comparable sensitivity and significantly higher specificity compared to IFA (p=0.34 and p<0.001, respectively). Conclusions The low specificity of STIC was caused by the low specificity of IFA IgM. Neither STIC nor IFA IgM can be used as reference standards against which to evaluate alternative diagnostic tests. Further evaluation of new diagnostic tests should be done with a carefully selected set of diagnostic tests and appropriate statistical models. PMID:26024375

  14. PAPER-64 Constraints On Reionization. II. The Temperature of the z =8.4 Intergalactic Medium

    NASA Astrophysics Data System (ADS)

    Pober, Jonathan C.; Ali, Zaki S.; Parsons, Aaron R.; McQuinn, Matthew; Aguirre, James E.; Bernardi, Gianni; Bradley, Richard F.; Carilli, Chris L.; Cheng, Carina; DeBoer, David R.; Dexter, Matthew R.; Furlanetto, Steven R.; Grobbelaar, Jasper; Horrell, Jasper; Jacobs, Daniel C.; Klima, Patricia J.; Kohn, Saul A.; Liu, Adrian; MacMahon, David H. E.; Maree, Matthys; Mesinger, Andrei; Moore, David F.; Razavi-Ghods, Nima; Stefan, Irina I.; Walbrugh, William P.; Walker, Andre; Zheng, Haoxuan

    2015-08-01

    We present constraints on both the kinetic temperature of the intergalactic medium (IGM) at z = 8.4, and on models for heating the IGM at high-redshift with X-ray emission from the first collapsed objects. These constraints are derived using a semi-analytic method to explore the new measurements of the 21 cm power spectrum from the Donald C. Backer Precision Array for Probing the Epoch of Reionization (PAPER), which were presented in a companion paper, Ali et al. Twenty-one cm power spectra with amplitudes of hundreds of mK2 can be generically produced if the kinetic temperature of the IGM is significantly below the temperature of the cosmic microwave background (CMB); as such, the new results from PAPER place lower limits on the IGM temperature at z = 8.4. Allowing for the unknown ionization state of the IGM, our measurements find the IGM temperature to be above ?5 K for neutral fractions between 10% and 85%, above ?7 K for neutral fractions between 15% and 80%, or above ?10 K for neutral fractions between 30% and 70%. We also calculate the heating of the IGM that would be provided by the observed high redshift galaxy population, and find that for most models, these galaxies are sufficient to bring the IGM temperature above our lower limits. However, there are significant ranges of parameter space that could produce a signal ruled out by the PAPER measurements; models with a steep drop-off in the star formation rate density at high redshifts or with relatively low values for the X-ray to star formation rate efficiency of high redshift galaxies are generally disfavored. The PAPER measurements are consistent with (but do not constrain) a hydrogen spin temperature above the CMB temperature, a situation which we find to be generally predicted if galaxies fainter than the current detection limits of optical/NIR surveys are included in calculations of X-ray heating.

  15. Immunoglobulins in the jejunal mucosa in adult coeliac disease and dermatitis herpetiformis after the reintroduction of dietary gluten.

    PubMed Central

    Lancaster-Smith, M; Joyce, S; Kumar, P

    1977-01-01

    Cells containing immunoglobulin (IgA, IgG, IgM) have been measured and the distribution of extracellular and epithelial cell immunoglobulin assessed in treated patients with adult coeliac disease (ACD) and dermatitis herpetiformis (DH) before and after gluten was reintroduced to the diet. Patients with ACD and DH frequently had IgM and IgG cells above the normal range even before re-exposure to gluten, although the range of IgA cells was normal. In both diseases IgA and IgM cells increased after gluten with a proportionally greater rise in the latter, so that numbers of IgM cells, but not of IgA, exceeded the control range in all but one patient. There were increased quantities of IgA and IgM extracellularly in the lamina propria and in epithelial cells after challenge with gluten. Third component of complement was also found in some biopsies after re-exposure to gluten. These findings support the suggestion that gluten induces a humoral immunological response within the small intestinal mucosa and that both IgA and IgM systems are involved. PMID:338443

  16. Preheating of the Universe by cosmic rays from primordial supernovae at the beginning of cosmic reionization

    NASA Astrophysics Data System (ADS)

    Sazonov, S.; Sunyaev, R.

    2015-12-01

    The 21-cm signal from the cosmic reionization epoch can shed light on the history of heating of the primordial intergalactic medium (IGM) at z ˜ 30-10. It has been suggested that X-rays from the first accreting black holes could significantly heat the Universe at these early epochs. Here we propose another IGM heating mechanism associated with the first stars. As known from previous work, the remnants of powerful supernovae (SNe) ending the lives of massive Population III stars could readily expand out of their host dark matter minihaloes into the surrounding IGM, aided by the preceding photo-evaporation of the halo's gas by the UV radiation from the progenitor star. We argue that during the evolution of such a remnant, a significant fraction of the SN kinetic energy can be put into low-energy (E ≲ 30 MeV) cosmic rays that will eventually escape into the IGM. These subrelativistic cosmic rays could propagate through the Universe and heat the IGM by ˜10-100 K by z ˜ 15, before more powerful reionization/heating mechanisms associated with the first galaxies and quasars came into play. Future 21-cm observations could thus constrain the energetics of the first SNe and provide information on the magnetic fields in the primordial IGM.

  17. Unveiling the nature of dark matter with high redshift 21 cm line experiments

    SciTech Connect

    Evoli, C.; Mesinger, A.; Ferrara, A. E-mail: andrei.mesinger@sns.it

    2014-11-01

    Observations of the redshifted 21 cm line from neutral hydrogen will open a new window on the early Universe. By influencing the thermal and ionization history of the intergalactic medium (IGM), annihilating dark matter (DM) can leave a detectable imprint in the 21 cm signal. Building on the publicly available 21cmFAST code, we compute the 21 cm signal for a 10 GeV WIMP DM candidate. The most pronounced role of DM annihilations is in heating the IGM earlier and more uniformly than astrophysical sources of X-rays. This leaves several unambiguous, qualitative signatures in the redshift evolution of the large-scale (k?0.1 Mpc{sup -1}) 21 cm power amplitude: (i) the local maximum (peak) associated with IGM heating can be lower than the other maxima; (ii) the heating peak can occur while the IGM is in emission against the cosmic microwave background (CMB); (iii) there can be a dramatic drop in power (a global minimum) corresponding to the epoch when the IGM temperature is comparable to the CMB temperature. These signatures are robust to astrophysical uncertainties, and will be easily detectable with second generation interferometers. We also briefly show that decaying warm dark matter has a negligible role in heating the IGM.

  18. Suppression of Immunoglobulin G Synthesis as a Result of Antibody-Mediated Suppression of Immunoglobulin M Synthesis in Chickens*

    PubMed Central

    Kincade, Paul W.; Lawton, Alexander R.; Bockman, Dale E.; Cooper, Max D.

    1970-01-01

    Development of heterogeneity of immunoglobulin classes has been investigated in the chicken by studying the effects of antibody-mediated suppression of IgM synthesis. Treatment of 13-day embryos with purified goat antibodies to IgM resulted in the elimination of IgM-containing cells from the bursa of Fabricius of 16- and 19-day embryos. When combined with bursectomy at hatching, administration of anti-IgM in ovo suppressed the synthesis not only of IgM but also of IgG. A number of experimental birds lacked detectable circulating immunoglobulins, plasma cells, and germinal centers when killed at 10 weeks of age. Contrasting results were obtained when IgM synthesis was suppressed after bursectomy at hatching. Birds so treated produced little or no IgM but synthesized normal amounts of IgG. The results suggest that, within the bursal environment, IgG-producing cells arise exclusively from cells that previously synthesized IgM. A model for generation of antibody variability is presented. Images PMID:5275387

  19. Mobilizable narrow host range plasmids as natural suicide vectors enabling horizontal gene transfer among distantly related bacterial species.

    PubMed

    Smorawinska, Maria; Szuplewska, Magdalena; Zaleski, Piotr; Wawrzyniak, Pawe?; Maj, Anna; Plucienniczak, Andrzej; Bartosik, Dariusz

    2012-01-01

    Klebsiella pneumoniae 287-w carries three small narrow host range (NHR) plasmids (pIGMS31, pIGMS32, and pIGRK), which could be maintained in several closely related species of Gammaproteobacteria, but not in Alphaproteobacteria. The plasmids contain different mobilization systems (MOB), whose activity in Escherichia coli was demonstrated in the presence of the helper transfer system originating from plasmid RK2. The MOBs of pIGMS31 and pIGMS32 are highly conserved in many bacterial plasmids (members of the MOB family), while the predicted MOB of pIGRK has a unique structure, encoding a protein similar to phage-related integrases. The MOBs of pIGMS31 and pIGMS32 enabled the transfer of heterologous replicons from E. coli into both gammaproteobacterial and alphaproteobacterial hosts, which suggests that these NHR plasmids contain broad host range MOB systems. Such plasmids therefore represent efficient carrier molecules, which may act as natural suicide vectors promoting the spread of diverse genetic information (including other types of mobile elements, e.g. resistance transposons) among evolutionarily distinct bacterial species. Thus, mobilizable NHR plasmids may play a much more important role in horizontal gene transfer than previously thought. PMID:22092700

  20. Redshifted 21 cm Emission from Minihalos before Reionization

    NASA Astrophysics Data System (ADS)

    Furlanetto, Steven R.; Oh, S. Peng

    2006-12-01

    Before reionization, the intergalactic medium (IGM) may have been sufficiently cold for low-mass ``minihalos'' to condense out of the gas and subsequently affect reionization. Previous work has shown that minihalos generate reasonably large 21 cm fluctuations. Here we consider this signal in its proper cosmological context and show that isolating minihalos from the rest of the IGM is extremely difficult. Using the well-known halo model, we compute the power spectrum of 21 cm fluctuations from minihalos and show that the signal decreases rapidly as feedback increases the Jeans mass. We then show that even a small Ly? background increases the 21 cm fluctuations of the diffuse IGM well beyond those of the minihalos; because the mass fraction in the IGM is much larger, minihalos will lie buried within the IGM signal. The distinctive signatures of nonlinear bias and minihalo structure emerge only at much smaller scales, well beyond the resolution of any upcoming instrument. Using simple but representative reionization histories, we then show that the required Ly? background level is most likely achieved at z>~15, while minihalos are still rare, so that they are almost always degenerate with the diffuse IGM.

  1. ANISOTROPIC ACTIVE GALACTIC NUCLEUS OUTFLOWS AND ENRICHMENT OF THE INTERGALACTIC MEDIUM. II. METALLICITY

    SciTech Connect

    Barai, Paramita; Martel, Hugo; Germain, Joel

    2011-01-20

    We investigate the large-scale influence of outflows from active galactic nuclei (AGNs) in enriching the intergalactic medium (IGM) with metals in a cosmological context. We combine cosmological simulations of large-scale structure formation with a detailed model of metal enrichment, in which outflows expand anisotropically along the direction of least resistance, distributing metals into the IGM. The metals carried by the outflows are generated by two separate stellar populations: stars located near the central AGN, and stars located in the greater galaxy. Using this algorithm, we performed a series of five simulations of the propagation of AGN-driven outflows in a cosmological volume of size (128 h{sup -1} Mpc){sup 3} in a {Lambda}CDM universe, and analyze the resulting metal enrichment of the IGM. We found that the metallicity induced in the IGM is greatly dominated by AGNs having bolometric luminosity L>10{sup 9} L{sub sun}, sources with 10{sup 8} < L/L{sub sun} < 10{sup 9} having a negligible contribution. Our simulations produced an average IGM metallicity of [O/H] = -5 at z = 5.5, which then rises gradually, and remains relatively flat at a value [O/H] = -2.8 between z = 2 and z = 0. The ejection of metals from AGN host galaxies by AGN-driven outflows is found to enrich the IGM to >10%-20% of the observed values, the number dependent on redshift. The enriched IGM volume fractions are small at z>3, then rise rapidly to the following values at z = 0: 6%-10% of the volume enriched to [O/H]> - 2.5, 14%-24% volume to [O/H]> - 3, and 34%-45% volume to [O/H]> - 4. At z {>=} 2, there is a gradient of the induced enrichment, the metallicity decreasing with increasing IGM density, enriching the underdense IGM to higher metallicities, a trend more prominent with increasing anisotropy of the outflows. This can explain observations of the metal-enriched low-density IGM at z {approx} 3-4.

  2. Deep PDF parsing to extract features for detecting embedded malware.

    SciTech Connect

    Munson, Miles Arthur; Cross, Jesse S.

    2011-09-01

    The number of PDF files with embedded malicious code has risen significantly in the past few years. This is due to the portability of the file format, the ways Adobe Reader recovers from corrupt PDF files, the addition of many multimedia and scripting extensions to the file format, and many format properties the malware author may use to disguise the presence of malware. Current research focuses on executable, MS Office, and HTML formats. In this paper, several features and properties of PDF Files are identified. Features are extracted using an instrumented open source PDF viewer. The feature descriptions of benign and malicious PDFs can be used to construct a machine learning model for detecting possible malware in future PDF files. The detection rate of PDF malware by current antivirus software is very low. A PDF file is easy to edit and manipulate because it is a text format, providing a low barrier to malware authors. Analyzing PDF files for malware is nonetheless difficult because of (a) the complexity of the formatting language, (b) the parsing idiosyncrasies in Adobe Reader, and (c) undocumented correction techniques employed in Adobe Reader. In May 2011, Esparza demonstrated that PDF malware could be hidden from 42 of 43 antivirus packages by combining multiple obfuscation techniques [4]. One reason current antivirus software fails is the ease of varying byte sequences in PDF malware, thereby rendering conventional signature-based virus detection useless. The compression and encryption functions produce sequences of bytes that are each functions of multiple input bytes. As a result, padding the malware payload with some whitespace before compression/encryption can change many of the bytes in the final payload. In this study we analyzed a corpus of 2591 benign and 87 malicious PDF files. While this corpus is admittedly small, it allowed us to test a system for collecting indicators of embedded PDF malware. We will call these indicators features throughout the rest of this report. The features are extracted using an instrumented PDF viewer, and are the inputs to a prediction model that scores the likelihood of a PDF file containing malware. The prediction model is constructed from a sample of labeled data by a machine learning algorithm (specifically, decision tree ensemble learning). Preliminary experiments show that the model is able to detect half of the PDF malware in the corpus with zero false alarms. We conclude the report with suggestions for extending this work to detect a greater variety of PDF malware.

  3. Reionization in a cold dark matter universe: The feedback of galaxy formation on the intergalactic medium

    NASA Technical Reports Server (NTRS)

    Shapiro, Paul R.; Giroux, Mark L.; Babul, Arif

    1994-01-01

    We study the coupled evolution of the intergalactic medium (IGM) and the emerging structure in the universe in the context of the cold dark matter (CDM) model, with a special focus on the consequences of imposing reionization and the Gunn-Peterson constraint as a boundary condition on the model. We have calculated the time-varying density of the IGM by coupling our detailed, numerical calculations of the thermal and ionization balance and radiative transfer in a uniform, spatially averaged IGM of H and He, including the mean opacity of an evolving distribution of gas clumps which correspond to quasar absorption line clouds, to the linearized equations for the growth of density fluctuations in both the gaseous and dark matter components in a CDM universe. We use the linear growth equations to identify the fraction of the gas which must have collapsed out at each epoch, an approach similar in spirit to the so-called Press-Schechter formalism. We identify the IGM density with the uncollapsed baryon fraction. The collapsed fraction is postulated to be a source of energy injection into the IGM, by radiation or bulk hydrodynamical heating (e.g., via shocks) or both, at a rate which is marginally enough to satisfy the Gunn-Peterson constraint at z less than 5. Our results include the following: (1) We find that the IGM in a CDM model must have contained a substantial fraction of the total baryon density of the universe both during and after its reionization epoch. (2) As a result, our previous conclusion that the observed Quasi-Stellar Objects (QSOs) at high redshift are not sufficient to ionize the IGM enough to satisfy the Gunn-Peterson constraint is confirmed. (3) We predict a detectable He II Gunn-Peterson effect at 304(1 + z) A in the spectra of quasars at a range of redshift z greater than or approx. 3, depending on the nature of the sources of IGM reionization. (4) We find, moreover, that a CDM model with high bias parameter b (i.e., b greater than or approx. 2) cannot account for the baryon content of the universe at z approximately 3 observed in quasar absorption line gas unless Omega (sub B) significantly exceeds the maximum value allowed by big bang nucleocynthesis. (5) For a CDM model with bias parameter within the allowed range of (lower) values, the lower limit to Omega(sub B) imposed by big bang nucleosynthesis (Omega(sub B) h(sup 2) greater than or equal to 0.01) combines with our results to yield the minimum IGM density for the CDM fodel. For CDM with b = 1 (Cosmic Background Explorer (COBE) normalization), we find Omega(sub IGM)(sup min) (z approximately 4) approx. equal 0.02-0.03, and Omega(sub IGM)(sup min)(z approximately 0) approx. equal 0.005-0.03, depending upon the nature of the sources of IGM reionization. (6) In general, we find that self-consistent reionization of the IGM by the collapsed baryon fraction has a strong effect on the rate of collapse. (7) As a further example, we show that the feedback effect on the IGM of energy release by the collapsed baryon fraction may explain the slow evolution of the observed comoving QSO number density between z = 5 and z = 2, followed by the sharp decline after z = 2.

  4. Diagnostic Potential and Antigenic Properties of Recombinant Tick-Borne Encephalitis Virus Subviral Particles Expressed in Mammalian Cells from Semliki Forest Virus Replicons

    PubMed Central

    Kuivanen, Suvi; Matveev, Andrey; Swaminathan, Sathyamangalam; Jskelinen-Hakala, Anu; Vapalahti, Olli

    2014-01-01

    The precursor membrane envelope (prME) proteins of all three tick-borne encephalitis virus (TBEV) subtypes were produced based on expression from Semliki Forest virus (SFV) replicons transcribed from recombinant plasmids. Vero E6 cells transfected by these plasmids showed specific reactivities in immunofluorescence and immunoblot assays by monoclonal antibodies against European and Far-Eastern subtype strains of TBEV, indicating proper folding of the expressed glycoproteins. The prME glycoproteins were secreted into the cell culture supernatant, forming TBEV subviral particles of 20 to 30 nm in diameter. IgM ?-capture and IgG monoclonal antibody (MAb)-capture enzyme immunoassays (EIAs) were developed based on prME Karelia-94 (Siberian subtype) particles. Altogether, 140 human serum samples were tested using these assays, and the results were compared to those obtained with a commercial IgM EIA, an in-house ?-capture IgM assay based on baculovirus-expressed antigen, a commercial IgG EIA, and a hemagglutination inhibition test. Compared to reference enzyme-linked immunosorbent assays (ELISAs), the sensitivities of the generated ?-capture IgM SFV-prME and IgG MAb-capture SFV-prME EIAs were 97.4 to 100% and 98.7%, respectively, and the specificities of the two assays were 100%. IgM and IgG immunofluorescence assays (IFAs) were created based on Vero E6 cells transfected with the recombinant plasmid carrying the TBEV Karelia-94 prME glycoproteins. The IgM IFA was 100% concordant with the ?-capture IgM bac-prME ELISA. The IgG IFA sensitivity and specificity were 98.7% and 100%, respectively, compared to those of the commercial ELISA. In conclusion, the tests developed based on SFV replicon-driven expression of TBEV glycoproteins provide safe and robust alternatives for conducting TBEV serology. PMID:24371235

  5. Studying reionization with the next generation of Ly? emitter surveys

    NASA Astrophysics Data System (ADS)

    Jensen, H.; Hayes, M.; Iliev, I. T.; Laursen, P.; Mellema, G.; Zackrisson, E.

    2014-11-01

    We study the prospects for constraining the ionized fraction of the intergalactic medium (IGM) at z > 6 with the next generation of large Ly? emitter surveys. We make predictions for the upcoming Subaru Hyper Suprime-Cam (HSC) Ly? survey and a hypothetical spectroscopic survey performed with the James Webb Space Telescope (JWST). Considering various scenarios where the observed evolution of the Ly? luminosity function of Ly? emitters at z > 6 is explained partly by an increasingly neutral IGM and partly by intrinsic galaxy evolution, we show how clustering measurements will be able to distinguish between these scenarios. We find that the HSC survey should be able to detect the additional clustering induced by a neutral IGM if the global IGM neutral fraction is greater than 20 per cent at z = 6.5. If measurements of the Ly? equivalent widths (EWs) are also available, neutral fractions as small as 10 per cent may be detectable by looking for correlation between the EW and the local number density of objects. In this case, if it should turn out that the IGM is significantly neutral at z = 6.5 and the intrinsic EW distribution is relatively narrow, the observed EWs can also be used to construct a map of the locations and approximate sizes of the largest ionized regions. For the JWST survey, the results appear a bit less optimistic. Since such surveys probe a large range of redshifts, the effects of the IGM will be mixed up with any intrinsic galaxy evolution that is present, making it difficult to disentangle the effects. However, we show that a survey with the JWST will have a possibility of observing a large group of galaxies at z 7, which would be a strong indication of a partially neutral IGM.

  6. THE 21 cm FOREST AS A PROBE OF THE REIONIZATION AND THE TEMPERATURE OF THE INTERGALACTIC MEDIUM

    SciTech Connect

    Xu Yidong; Fan Zuhui; Chen Xuelei; Trac, Hy; Cen, Renyue

    2009-10-20

    Using high-redshift radio sources as background, the 21 cm forest observations probe the neutral hydrogen absorption signatures of early structures along the lines of sight. Directly sensitive to the spin temperature of the hydrogen atoms, it complements the 21 cm tomography observations, and provides information on the temperature as well as the ionization state of the intergalactic medium (IGM). We use a radiative transfer simulation to investigate the 21 cm forest signals during the epoch of reionization. We first confirmed that the optical depth and equivalent width (EW) are good representations of the ionization and thermal state of the IGM. The features selected by their relative optical depth are excellent tracers of ionization fields, and the features selected by their absolute optical depth are very sensitive to the IGM temperature, so the IGM temperature information could potentially be extracted from 21 cm forest observation, thus breaking a degeneracy in 21 cm tomographic observation. With the EW statistics, we predict some observational consequences for 21 cm forest. From the distributions of EWs and the number evolution of absorbers and leakers with different EWs, we see clearly the cosmological evolution of ionization state of the IGM. The number density of potentially observable features decreases rapidly with increasing gas temperature. The sensitivity of the proposed EW statistic to the IGM temperature makes it a unique and potentially powerful probe of reionization. Missing small-scale structures, such as small filaments and minihalos that are unresolved in our current simulation, and lack of an accurate calculation of the IGM temperature, however, likely have rendered the presented signals quantitatively inaccurate. Finally, we discuss the requirements of the background radio sources for such observations, and find that signals with equivalent widths larger than 1 kHz are hopeful to be detected.

  7. Problem of immunoglobulin M co-detection in serological response to bacterial and viral respiratory pathogens among children suspected of legionellosis

    PubMed Central

    2015-01-01

    The objective of this research was an analysis of the serological response to respiratory bacterial and viral pathogens, in 156 children admitted to hospital in Warsaw with a suspicion of legionellosis. Levels of immunoglobulin (Ig) M to Bordetella pertussis, Mycoplasma pneumoniae, respiratory syncytial virus (RSV), adenoviruses, human parainfluenza virus (HPIV) t. 1-4 and influenza t. A + B viruses were determined retrospectively by ELISAs. In the prospective examinations (only Legionella pneumophila sg1), a positive level of IgM was found in 35 patients, but in 59 children together with retrospective tests. There were positive results for B. pertussis (21 children), followed by HPIV (10 children), M. pneumoniae (5 patients), RSV (4 persons), adenoviruses (3 children), and influenza A + B virus (3 persons). Positive results for > 1 agent were found in 16 children. The most often co-detected IgM were to L. pneumophila sg1 and B. pertussis (9 children) and L. pneumophila sg1 and M. pneumoniae (5 patients). The distribution of IgM to L. pneumophila sg1, B. pertussis and HPIV among children ≤ 4 years differed significantly from IgM specific to other pathogens. A high number of HPIV infections, mainly single, was found among infants. Positive results of IgM to L. pneumophila sg1 were mainly found in children aged 4-5 years. and the oldest children (over 10 years.). However, among the oldest children, anti-L. pneumophila sg1 antibodies were often found together with IgM to B. pertussis. Infections due to more than 2 pathogens were only observed among patients with pneumonia, especially due to L. pneumophila sg1 and/or B. pertussis. Conversely, co-detection of IgM ELISA for L. pneumophila and M. pneumoniae were mainly detected among patients hospitalized without pneumonia. PMID:26557031

  8. The reionization of the universe: The feedback of galaxy formation on the intergalactic medium

    NASA Technical Reports Server (NTRS)

    Shapiro, Paul R.; Giroux, Mark L.

    1993-01-01

    The thermal and ionization evolution of a uniform intergalactic medium (IGM) composed of H and He, undergoing reionization, including the mean effect of gas clumps embedded in a smoothly distributed ambient gas were calculated. The rate equations for ionization and recombination were solved together with the equations of energy conservation, including the effects of cosmological expansion, radiative and Compton cooling, and the diffuse flux emitted by the gas, and radiative transfer. The contribution to the continuum opacity of the universe due to the observed quasar absorption line clouds (QALC'S) were included. A variety of sources of photoionization, including quasars and primeval galaxies, as well as the possibility that hydrodynamical processes deposit thermal energy in the IGM were considered. Applications of these calculations including the evolution of the Ly-alpha forest clouds are described. A self-consistent treatment of the thermal and ionization history of the intergalactic medium (IGM) must take account of the growth of structure in the universe, since the mean density of the IGM corresponds primarily to the time-varying uncollapsed fraction of the baryon-electron component of the matter, and the collapsed fraction, in turn, can have a feedback effect on this uncollapsed fraction by releasing ionizing radiation and thermal energy and by contributing to the opacity of the universe. The coupled evolution of the IGM and the emerging structure with a special focus on the reionization of the IGM, which is believed to have been completed by some redshift z is approximately greater than 4, as inferred from the absence of the Gunn-Peterson effect in the spectra of high z quasars, are studied. The results and implications of detailed, numerical calculations of the thermal and ionization balance and radiative transfer in a uniform IGM of H and He, including the mean effect of an evolving distribution of gas clumps embedded in a smoothly distributed ambient gas is described.

  9. Tyrosine sulfation is a trans-Golgi-specific protein modification

    SciTech Connect

    Baeuerle, P.A.; Huttner, W.B.

    1987-12-01

    The trans-Golgi has been recognized as having a key role in terminal glycosylation and sorting of proteins. Here we show that tyrosine sulfation, a frequent modification of secretory proteins, occurs specifically in the trans-Golgi. The heavy chain of immunoglobulin M (IgM) produced by hybridoma cells was found to contain tyrosine sulfate. This finding allowed the comparison of the state of sulfation of the heavy chain with the state of processing of its N-linked oligosaccharides. First, the pre-trans-Golgi forms of the IgM heavy chain, which lacked galactose and sialic acid, were unsulfated, whereas the trans-Golgi form, identified by the presence of galactose and sialic acid, and the secreted form of the IgM heavy chain were sulfated. Second, the earliest form of the heavy chain detectable by sulfate labeling, as well as the heavy chain sulfated in a cell-free system in the absence of vesicle transport, already contained galactose and sialic acid. Third, sulfate-labeled IgM moved to the cell surface with kinetics identical to those of galactose-labeled IgM. Lastly, IgM labeled with sulfate at 20/sup 0/C was not transported to the cell surface at 20/sup 0/C but reached the cell surface at 37/sup 0/C. The data suggest that within the trans-Golgi, tyrosine sulfation of IgM occurred at least in part after terminal glycosylation and therefore appeared to be the last modification of this constitutively secreted protein before its exit from this compartment. Furthermore, the results establish the covalent modification of amino acid side chains as a novel function of the trans-Golgi.

  10. Dissection of the human antigammaglobulin idiotype system with monoclonal antibodies.

    PubMed

    Posnett, D N; Wisniewolski, R; Pernis, B; Kunkel, H G

    1986-02-01

    Murine monoclonal antibodies (MoAb) were prepared by immunizing mice with human monoclonal rheumatoid factors from patients with mixed cryoglobulinaemia. Indirect solid phase radioimmunoassay and haemagglutination inhibition were used to screen the MoAb. Reactivity patterns of MoAb were determined using (a) polyclonal and monoclonal IgM proteins, (b) monoclonal IgM proteins from patients with neuropathy, (c) monoclonal and polyclonal IgM antigammaglobulins, and (d) various isolated VkIIIb-positive immunoglobulins. Several patterns were obtained: MoAb reacting with private idiotypic determinants, with VkIIIb-related determinants, and with cross-reactive idiotypes (CRI). Two MoAb of the second type reacted with VkIIIb-positive immunoglobulins and light chains regardless of their antigenic activity. Another MoAb reacted with VkIII light chains only when in association with mu heavy chains. MoAb of the third type defined distinct CRI systems. One of these was restricted to antigammaglobulins and another also involved neuropathy-associated monoclonal IgM proteins. All MoAb clearly reacted with a minor population of normal polyclonal IgM, except for the MoAb detecting private idiotypic determinants. Studies using inhibition of binding by enzyme-linked immunosorbent assay showed that polyclonal IgM antigammaglobulins may carry a CRI determinant detected by one of the MoAb. This CRI system, defined by the MoAb Glo 86.3, was similar to but not identical with the previously described Wa CRI, which is widely prevalent among IgM antigammaglobulins of rheumatoid arthritis. PMID:2419964

  11. Adaptive prior probability and spatial temporal intensity change estimation for segmentation of the one-year-old human brain

    PubMed Central

    Kim, Sun Hyung; Fonov, Vladimir; Dietrich, Cheryl; Vachet, Clement; Hazlett, Heather C.; Smith, Rachel G.; Graves, Mike; Piven, Joseph; Gilmore, John H.; Collins, D. Louis; Gerig, Guido; Styner, Martin

    2012-01-01

    The degree of white matter (WM) myelination is rather inhomogeneous across the brain. White matter appears differently across the cortical lobes in MR images acquired during early postnatal development. Specifically at 1-year of age, the gray/white matter contrast of MR T1 and T2 weighted images in prefrontal and temporal lobes is reduced as compared to the rest of the brain, and thus, tissue segmentation results commonly show lower accuracy in these lobes. In this novel work, we propose the use of spatial intensity growth maps (IGM) for T1 and T2 weighted images to compensate for local appearance inhomogeneity. The IGM captures expected intensity changes from 1 to 2 years of age, as appearance homogeneity is greatly improved by the age of 24 months. The IGM was computed as the coefficient of a voxel-wise linear regression model between corresponding intensities at 1 and 2 years. The proposed IGM method revealed low regression values of 110% in GM and CSF regions, as well as in WM regions at maturation stage of myelination at 1 year. However, in the prefrontal and temporal lobes we observed regression values of 2025%, indicating that the IGM appropriately captures the expected large intensity change in these lobes mainly due to myelination. The IGM is applied to cross-sectional MRI datasets of 1-year-old subjects via registration, correction and tissue segmentation of the IGM-corrected dataset. We validated our approach in a small leave-one-out study of images with known, manual ground truth segmentations. PMID:23032117

  12. Laboratory confirmation of measles in elimination settings: experience from the Republic of the Marshall Islands, 2003

    PubMed Central

    Nandy, Robin; Hickman, Carole J; Langidrik, Justina R; Strebel, Peter M; Papania, Mark J; Seward, Jane F; Bellini, William J

    2009-01-01

    Abstract Objective To highlight the complications involved in interpreting laboratory tests of measles immunoglobulin M (IgM) for confirmation of infection during a measles outbreak in a highly vaccinated population after conducting a mass immunization campaign as a control measure. Methods This case study was undertaken in the Republic of the Marshall Islands during a measles outbreak in 2003, when response immunization was conducted. A measles case was defined as fever and rash and one or more of cough, coryza or conjunctivitis. Between 13 July and 7 November 2003, serum samples were obtained from suspected measles cases for serologic testing and nasopharyngeal swabs were taken for viral isolation by reverse transcriptase polymerase chain reaction (RT–PCR). Findings Specimens were collected from 201 suspected measles cases (19% of total): of the ones that satisfied the clinical case definition, 45% were IgM positive (IgM+) and, of these, 24% had received measles vaccination within the previous 45 days (up to 45 days after vaccination an IgM+ result could be due to either vaccination or wild-type measles infection). The proportion of IgM+ results varied with clinical presentation, the timing of specimen collection and vaccination status. Positive results on RT–PCR occurred in specimens from eight IgM-negative and four IgM+ individuals who had recently been vaccinated. Conclusion During measles outbreaks, limiting IgM testing to individuals who meet the clinical case definition and have not been recently vaccinated allows for measles to be confirmed while conserving resources. PMID:19274360

  13. Collecting Autonomous Spreading Malware Using High-Interaction Honeypots

    NASA Astrophysics Data System (ADS)

    Zhuge, Jianwei; Holz, Thorsten; Han, Xinhui; Song, Chengyu; Zou, Wei

    Autonomous spreading malware in the form of worms or bots has become a severe threat in today's Internet. Collecting the sample as early as possible is a necessary precondition for the further treatment of the spreading malware, e.g., to develop antivirus signatures. In this paper, we present an integrated toolkit called HoneyBow, which is able to collect autonomous spreading malware in an automated manner using high-interaction honeypots. Compared to low-interaction honeypots, HoneyBow has several advantages due to a wider range of captured samples and the capability of collecting malware which propagates by exploiting new vulnerabilities. We validate the properties of HoneyBow with experimental data collected during a period of about nine months, in which we collected thousands of malware binaries. Furthermore, we demonstrate the capability of collecting new malware via a case study of a certain bot.

  14. A Study on Architecture of Malicious Code Blocking Scheme with White List in Smartphone Environment

    NASA Astrophysics Data System (ADS)

    Lee, Kijeong; Tolentino, Randy S.; Park, Gil-Cheol; Kim, Yong-Tae

    Recently, the interest and demands for mobile communications are growing so fast because of the increasing prevalence of smartphones around the world. In addition, the existing feature phones were replaced by smartphones and it has widely improved while using the explosive growth of Internet users using smartphones, e-commerce enabled Internet banking transactions and the importance of protecting personal information. Therefore, the development of smartphones antivirus products was developed and launched in order to prevent malicious code or virus infection. In this paper, we proposed a new scheme to protect the smartphone from malicious codes and malicious applications that are element of security threats in mobile environment and to prevent information leakage from malicious code infection. The proposed scheme is based on the white list smartphone application which only allows installing authorized applications and to prevent the installation of malicious and untrusted mobile applications which can possibly infect the applications and programs of smartphones.

  15. Tyrosinase Inhibitory Effects and Antioxidative Activities of Saponins from Xanthoceras Sorbifolia Nutshell

    PubMed Central

    Zhang, Hongmei; Zhou, Quancheng

    2013-01-01

    Certain saponins are bioactive compounds with anticancer, antivirus and antioxidant activities. This paper discussed inhibitory effects of saponins from Xanthoceras Sorbifolia on tyrosinase, through the research of the rate of tyrosinase catalyzed L-DOPA oxidation. The inhibition rate of tyrosinase activity presented non-linear changes with the saponins concentration. The rate reached 52.0% when the saponins concentration was 0.96 mg/ml. Antioxidant activities of saponins from Xanthoceras Sorbifolia were evaluated by using hydroxyl and superoxide radical scavenging assays. The hydroxyl radical scavenging effects of the saponins were 15.568.7%, respectively at the concentration of 0.182.52 mg/ml. The superoxide radical scavenging activity reduced from 96.6% to 7.05% with the time increasing at the concentration of 1.44 mg/ml. All the above antioxidant evaluation indicated that saponins from Xanthoceras Sorbifolia exhibited good antioxidant activity in a concentration- dependent manner. PMID:23990897

  16. The Unknown Computer Viruses Detection Based on Similarity

    NASA Astrophysics Data System (ADS)

    Liu, Zhongda; Nakaya, Naoshi; Koui, Yuuji

    New computer viruses are continually being generated and they cause damage all over the world. In general, current anti-virus software detects viruses by matching a pattern based on the signature; thus, unknown viruses without any signature cannot be detected. Although there are some static analysis technologies that do not depend on signatures, virus writers often use code obfuscation techniques, which make it difficult to execute a code analysis. As is generally known, unknown viruses and known viruses share a common feature. In this paper we propose a new static analysis technology that can circumvent code obfuscation to extract the common feature and detect unknown viruses based on similarity. The results of evaluation experiments demonstrated that this technique is able to detect unknown viruses without false positives.

  17. Interaction of nanodiamonds materials with influenza viruses

    NASA Astrophysics Data System (ADS)

    Ivanova, V. T.; Ivanova, M. V.; Spitsyn, B. V.; Garina, K. O.; Trushakova, S. V.; Manykin, A. A.; Korzhenevsky, A. P.; Burseva, E. I.

    2012-02-01

    The perspectives of the application of modern materials contained nanodiamonds (ND) are considered in this study. The interaction between detonation paniculate ND, soot and influenza A and B viruses, fragments of cDNA were analyzed at the normal conditions. It was shown that these sorbents can interact with the following viruses: reference epidemic strains of influenza A(H1N1), A(H1N1)v, A(H3N2) and B viruses circulated in the word in 2000-2010. The allantoises, concentrated viruses, cDNA can be absorbed by ND sorbents and getting removed from water solutions within 20 min. ND sorbents can be used for the preparation of antivirus filters for water solution and for future diagnostic systems in virology.

  18. The effect of infected external computers on the spread of viruses: A compartment modeling study

    NASA Astrophysics Data System (ADS)

    Yang, Lu-Xing; Yang, Xiaofan

    2013-12-01

    Inevitably, there exist infected computers outside of the Internet. This paper aims to understand how infected external computers affect the spread of computer viruses. For that purpose, a new virus-antivirus spreading model, which takes into account the effect of infected/immune external computers, is established. A systematic study shows that, unlike most previous models, the proposed model admits no virus-free equilibrium and admits a globally asymptotically stable viral equilibrium. This result implies that it would be practically impossible to eradicate viruses on the Internet. As a result, inhibiting the virus prevalence to below an acceptable level would be the next best thing. A theoretical study reveals the effect of different parameters on the steady virus prevalence. On this basis, a number of suggestions are made so as to contain virus spreading.

  19. Studying classical swine fever virus: making the best of a bad virus.

    PubMed

    Ji, Wei; Guo, Zhen; Ding, Nai-Zheng; He, Cheng-Qiang

    2015-02-01

    Classical swine fever (CSF) is a highly contagious and often fatal disease that affects domestic pigs and wild boars. Outbreak of CSF can cause heavy economic losses to the pig industry. The strategies to prevent, control and eradicate CSF disease are based on containing the disease through a systematic prophylactic vaccination policy and a non-vaccination stamping-out policy. The quest for prevention, control and eradication of CSF has moved research forward in academia and industry, and has produced noticeable advances in understanding fundamental aspects of the virus replication mechanisms, virulence, and led to the development of new vaccines. In this review we summarize recent progress in CSFV epidemiology, molecular features of the genome and proteome, the molecular basis of virulence, and the development of anti-virus technologies. PMID:25510481

  20. Access Control of Web and Java Based Applications

    NASA Technical Reports Server (NTRS)

    Tso, Kam S.; Pajevski, Michael J.; Johnson, Bryan

    2011-01-01

    Cyber security has gained national and international attention as a result of near continuous headlines from financial institutions, retail stores, government offices and universities reporting compromised systems and stolen data. Concerns continue to rise as threats of service interruption, and spreading of viruses become ever more prevalent and serious. Controlling access to application layer resources is a critical component in a layered security solution that includes encryption, firewalls, virtual private networks, antivirus, and intrusion detection. In this paper we discuss the development of an application-level access control solution, based on an open-source access manager augmented with custom software components, to provide protection to both Web-based and Java-based client and server applications.

  1. Global dynamics of a novel multi-group model for computer worms

    NASA Astrophysics Data System (ADS)

    Gong, Yong-Wang; Song, Yu-Rong; Jiang, Guo-Ping

    2013-04-01

    In this paper, we study worm dynamics in computer networks composed of many autonomous systems. A novel multi-group SIQR (susceptible-infected-quarantined-removed) model is proposed for computer worms by explicitly considering anti-virus measures and the network infrastructure. Then, the basic reproduction number of worm R0 is derived and the global dynamics of the model are established. It is shown that if R0 is less than or equal to 1, the disease-free equilibrium is globally asymptotically stable and the worm dies out eventually, whereas, if R0 is greater than 1, one unique endemic equilibrium exists and it is globally asymptotically stable, thus the worm persists in the network. Finally, numerical simulations are given to illustrate the theoretical results.

  2. A study of malware detection on smart mobile devices

    NASA Astrophysics Data System (ADS)

    Yu, Wei; Zhang, Hanlin; Xu, Guobin

    2013-05-01

    The growing in use of smart mobile devices for everyday applications has stimulated the spread of mobile malware, especially on popular mobile platforms. As a consequence, malware detection becomes ever more critical in sustaining the mobile market and providing a better user experience. In this paper, we review the existing malware and detection schemes. Using real-world malware samples with known signatures, we evaluate four popular commercial anti-virus tools and our data shows that these tools can achieve high detection accuracy. To deal with the new malware with unknown signatures, we study the anomaly based detection using decision tree algorithm. We evaluate the effectiveness of our detection scheme using malware and legitimate software samples. Our data shows that the detection scheme using decision tree can achieve a detection rate up to 90% and a false positive rate as low as 10%.

  3. Design of Cyber Attack Precursor Symptom Detection Algorithm through System Base Behavior Analysis and Memory Monitoring

    NASA Astrophysics Data System (ADS)

    Jung, Sungmo; Kim, Jong Hyun; Cagalaban, Giovanni; Lim, Ji-Hoon; Kim, Seoksoo

    More recently, botnet-based cyber attacks, including a spam mail or a DDos attack, have sharply increased, which poses a fatal threat to Internet services. At present, antivirus businesses make it top priority to detect malicious code in the shortest time possible (Lv.2), based on the graph showing a relation between spread of malicious code and time, which allows them to detect after malicious code occurs. Despite early detection, however, it is not possible to prevent malicious code from occurring. Thus, we have developed an algorithm that can detect precursor symptoms at Lv.1 to prevent a cyber attack using an evasion method of 'an executing environment aware attack' by analyzing system behaviors and monitoring memory.

  4. Structure-activity relationship of N-benzenesulfonyl matrinic acid derivatives as a novel class of coxsackievirus B3 inhibitors.

    PubMed

    Wang, Sheng-Gang; Kong, Lan-Ying; Li, Ying-Hong; Cheng, Xin-Yue; Su, Feng; Tang, Sheng; Bi, Chong-Wen; Jiang, Jian-Dong; Li, Yu-Huan; Song, Dan-Qing

    2015-09-01

    A novel series of N-benzenesulfonyl matrinic amine/amide and matrinic methyl ether analogues were designed, synthesized and evaluated for their in vitro anti-coxsackievirus B3 (CVB3) activities. The structure-activity relationship (SAR) studies revealed that introduction of a suitable amide substituent on position 4' could greatly enhance the antivirus potency. Compared to the lead compounds, the newly synthesized matrinic amide derivatives 21c-d and 21j exhibited stronger anti-CVB3 activities with lower micromolar IC50 from 2.5 ?M to 2.7 ?M, and better therapeutic properties with improved selectivity index (SI) from 63 to 67. The SAR results provided powerful information for further strategic optimization, and these top compounds were selected for the next evaluation as novel enterovirus inhibitors. PMID:26112440

  5. [Advance in study on pharmacological effect of Eucommiae Folium].

    PubMed

    Yuan, Tian-Yi; Fang, Lian-Hua; Lv, Yang; Du, Guan-Hu

    2013-03-01

    Eucommia ulmoides is a valuable traditional Chinese medicine, whose cortexes have long been used as medi cines. Due to the scarcity of its resources, people began using its leaves instead of cortexes in medicines. Eucommiae Folium and its leaves have many pharmacological effects and thereby being clinically applied as genuine traditional Chinese medicines. Modern pharmological studies have showed that Eucommiae Folium leaves have such effects as blood pressure reduction, blood lipid regulation, cardiovascular protection, anti-obesity, anti-inflammation, anti-virus, enhancement of immunologic function, resistance against senility and anti-fatigue. In clinic, Eucommiae Folium is mainly used to treat hypertention and obstetrical and gynecological disease. The essay summarizes the latest advance in domestic and foreign studie on pharmacological effeets and clinical applications of Eucommiae Folium leaves, and thus providing reference for studies on new drugs of Eucommiae Folium leave. PMID:23717951

  6. ISOLATION OF CAFFEIC ACID FROM EUPATORIUM ADENOPHORUM SPRENG BY HIGH-SPEED COUNTERCURRENT CHROMATOGRAPHY AND SYNTHESIS OF CAFFEIC ACID-INTERCALATED LAYERED DOUBLE HYDROXIDE

    PubMed Central

    Wei, Yun; Gao, Yali; Zhang, Kai; Ito, Yoichiro

    2010-01-01

    Preparative high-speed countercurrent chromatography (HSCCC) was successfully used for isolation and purification of caffeic acid from Eupatorium adenophorum Spreng with a solvent system composed of ethyl acetate-methanol-water at a volume ratio of 10:1:10, v/v. Using a preparative unit of the HSCCC centrifuge, about a 938 mg amount of the crude extract was separated, yielding 63.2 mg of caffeic acid at purity of 96.0%. Then, the anti-microbial and anti-virus drug caffeic acid (C9H8O4) was intercalated into layered double hydroxides for the first time by anion exchange under a nitrogen atmosphere. The product caffeic acidLDH has been characterized by powder X-ray diffraction (XRD), Fourier transform-infrared (FT-IR), Scanning electron micrographs (SEM), indicating that the drug has been successfully intercalated into LDH. PMID:20454592

  7. [Review of bioactivities of natural cycloartane triterpenoids].

    PubMed

    Tian, Ze; Xiao, Pei-gen; Wen, Jie; Huang, Feng; Yang, Meng-su; Chen, Shi-lin

    2006-04-01

    Cycloartane triterpenoids, which exist widely in nature, are mainly distributed in Astragalus (Leguminosae) species, Trib. Cimicifuga (Ranunculaceae) and Thalictrium (Ranunculaceae) species and possess various bioactivities. Along with the development of isolation techniques of phytochemistry, more and more this kind of compounds are isolated and identified. However, bioactivity researches on the compounds are relatively lagged behind. Most researches are still in screening level, deficient in mechanism elucidation, short of action proven in vivo and SAR analysis. The author summarized the bioactivity of this kind of compounds from all aspects: anti-tumor, anti-virus, antibacterial, anti-inflammation, immune-regulatory, cardiovascular system, hepatic protection and so forth. This will be benefit for the further research and development of the compounds. PMID:16830816

  8. Identification of Potential Serodiagnostic and Subunit Vaccine Antigens by Antibody Profiling of Toxoplasmosis Cases in Turkey*

    PubMed Central

    Liang, Li; D?kaya, Mert; Juarez, Silvia; Caner, Ay?e; Jasinskas, Algis; Tan, Xiaolin; Hajagos, Bettina E.; Bradley, Peter J.; Korkmaz, Metin; Grz, Yksel; Felgner, Philip L.; Davies, D. Huw

    2011-01-01

    Toxoplasmosis, caused by infection of the protozoan parasite Toxoplasma gondii, is associated with mild disease in healthy individuals, whereas individuals with depressed immunity may develop encephalitis, neurologic disorders, and other organ diseases. Women who develop acute toxoplasmosis during pregnancy are at risk of transmitting the infection to the fetus, which may lead to fetal damage. A diagnosis is usually confirmed by measuring IgG, or IgM where it is important to determine the onset of infection. A negative IgM result essentially excludes acute infection, whereas a positive IgM test is largely uninterpretable because IgM can persist for up to 18 months after infection. To identify antigens for improved diagnosis of acute infection, we probed protein microarrays displaying the polypeptide products of 1357 Toxoplasma exons with well-characterized sera from Turkey. The sera were classified according to conventional assays into (1) seronegative individuals with no history of T. gondii infection; (2) acute infections defined by clinical symptoms, high IgM titers, and low avidity IgG; (3) chronic/convalescent cases with high avidity IgG but persisting IgM; (iv) true chronic infections, defined by high avidity IgG and no IgM. We have identified 38 IgG target antigens and 108 IgM target antigens that can discriminate infected patients from healthy controls, one or more of which could form the basis of a tier-1? test to determine current or previous exposure. Of these, three IgG antigens and five IgM antigens have the potential to discriminate chronic/IgM persisting or true chronics from recent acutely infected patients (a tier-2? test). Our analysis of the antigens revealed several enriched features relative to the whole proteome, which include transmembrane domains, signal peptides, or predicted localization at the outer membrane. This is the first protein microarray survey of the antibody response to T. gondii, and will help in the development of improved serodiagnostics and vaccines. PMID:21512035

  9. Lentivirus-mediated expression of MxA in chicken spermatogonial stem cells.

    PubMed

    Liu, L; He, P; Cai, K; Zhang, Y; Li, J; Cao, F; Ding, Z; Zhang, N

    2010-10-01

    The aim of this study was to construct a lentivirus vector that carries the human myxovirus-resistant A (MxA) anti-virus gene for efficiently infecting rooster spermatogonial stem cells (SSCs). A lentiviral vector carrying the enhanced green fluorescent protein (EGFP) and MxA fusion gene (EGFP-MxA) was constructed using TOPO technology in this study. Enhanced green fluorescent protein-MxA was inserted in the right orientation as determined by restriction enzyme digest. No gene recombination in the vector occurred. After infecting 293FT cells, EGFP-MxA fusion protein was expressed as granular green fluorescence characteristic of EGFP-MxA expression, suggesting that the TOPO expression vector was properly constructed and the fusion protein expressed correctly. The EGFP-MxA recombinant lentivirus was packaged by cotransfecting 293FT cells with EGFP-MxA and the packaging plasmids. We also purified SSCs from testicle tissues from 25-day-old roosters for infection with the EGFP-MxA recombinant virus. After infecting rooster SSCs with the recombinant virus for 72 h, EGFP-MxA expression was detected by EGFP expression. Enhanced green fluorescent protein-MxA expression in SSCs was further confirmed at the transcription level by RT-PCR and at the protein level by immunocytochemistry. Staining with Hoechst 33342 showed that infected SSCs differed from the sertoli cells. Similar to stem cells, SSCs were positive for alkaline phosphoric acid enzyme and for stage-specific embryonic antigen-1 stem cell factor. The results demonstrated that the recombinant virus made in our study can infect rooster SSCs efficiently to express the anti-virus protein MxA, establishing the basis of transferring MxA into SSCs to obtain virus-resistant, genetically-modified roosters. PMID:20412511

  10. Baculoviruses Modulate a Proapoptotic DNA Damage Response To Promote Virus Multiplication

    PubMed Central

    Mitchell, Jonathan K.

    2012-01-01

    The baculovirus Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) initiates apoptosis in diverse insects through events triggered by virus DNA (vDNA) replication. To define the proapoptotic pathway and its role in antivirus defense, we investigated the link between the host's DNA damage response (DDR) and apoptosis. We report here that AcMNPV elicits a DDR in the model insect Drosophila melanogaster. Replication of vDNA activated DDR kinases, as evidenced by ATM-driven phosphorylation of the Drosophila histone H2AX homolog (H2Av), a critical regulator of the DDR. Ablation or inhibition of ATM repressed H2Av phosphorylation and blocked virus-induced apoptosis. The DDR kinase inhibitors caffeine and KU55933 also prevented virus-induced apoptosis in cells derived from the permissive AcMNPV host, Spodoptera frugiperda. This block occurred at a step upstream of virus-mediated depletion of the cellular inhibitor-of-apoptosis protein, an event that initiates apoptosis in Spodoptera and Drosophila. Thus, the DDR is a conserved, proapoptotic response to baculovirus infection. DDR inhibition also repressed vDNA replication and reduced virus yields 100,000-fold, demonstrating that the DDR contributes to virus production, despite its recognized antivirus role. In contrast to virus-induced phosphorylation of Drosophila H2Av, AcMNPV blocked phosphorylation of the Spodoptera H2AX homolog (SfH2AX). Remarkably, AcMNPV also suppressed SfH2AX phosphorylation following pharmacologically induced DNA damage. These findings indicate that AcMNPV alters canonical DDR signaling in permissive cells. We conclude that AcMNPV triggers a proapoptotic DDR that is subsequently modified, presumably to stimulate vDNA replication. Thus, manipulation of the DDR to facilitate multiplication is an evolutionarily conserved strategy among DNA viruses of insects and mammals. PMID:23035220

  11. Lack of security of networked medical equipment in radiology.

    PubMed

    Moses, Vinu; Korah, Ipeson

    2015-02-01

    OBJECTIVE. There are few articles in the literature describing the security and safety aspects of networked medical equipment in radiology departments. Most radiologists are unaware of the security issues. We review the security of the networked medical equipment of a typical radiology department. MATERIALS AND METHODS. All networked medical equipment in a radiology department was scanned for vulnerabilities with a port scanner and a network vulnerability scanner, and the vulnerabilities were classified using the Common Vulnerability Scoring System. A network sniffer was used to capture and analyze traffic on the radiology network for exposure of confidential patient data. We reviewed the use of antivirus software and firewalls on the networked medical equipment. USB ports and CD and DVD drives in the networked medical equipment were tested to see whether they allowed unauthorized access. Implementation of the virtual private network (VPN) that vendors use to access the radiology network was reviewed. RESULTS. Most of the networked medical equipment in our radiology department used vulnerable software with open ports and services. Of the 144 items scanned, 64 (44%) had at least one critical vulnerability, and 119 (83%) had at least one high-risk vulnerability. Most equipment did not encrypt traffic and allowed capture of confidential patient data. Of the 144 items scanned, two (1%) used antivirus software and three (2%) had a firewall enabled. The USB ports were not secure on 49 of the 58 (84%) items with USB ports, and the CD or DVD drive was not secure on 17 of the 31 (55%) items with a CD or DVD drive. One of three vendors had an insecure implementation of VPN access. CONCLUSION. Radiologists and the medical industry need to urgently review and rectify the security issues in existing networked medical equipment. We hope that the results of our study and this article also raise awareness among radiologists about the security issues of networked medical equipment. PMID:25615757

  12. [Clinical trials and intensive therapy of the swine flu (H1N1)].

    PubMed

    Nakashidze, I M; Tsintsadze, N G; Potskhishvili, Sh N; Dzhibladze, K M

    2012-01-01

    During the recent years there's a high index of the swine flu А (H1N1) disease in the whole world. In Georgia it began to spread at the end of Autumn 2009. The aim of our study was to define clinical trials of the swine flu (H1N1) in patients of Republic Clinical Hospital in Batumi from 2009 to 2011 and to generalize the methods of treatment. In the hospital there were 94 patients suffering from the swine flu (H1N1) disease, 20 of which due to their critical situation of the disease were treated in the department of the intensive therapy. We studied case histories of 20 patients, who were undergoing treatment in the department of the intensive therapy by the generally acknowledged programme of study and monitoring due to their hard disease. Among these 20 patients 10 were women and 10 men. 10 patients died. The programme of intensive treatment consisted of infusive-transfusive therapy by the negative water balance, antivirus treatment (Tamiflu/Relenza), de-escalation antibiotic therapy, mechanic ventilation of lungs, aerosol therapy, plus symptom treatment. In 2011 there were fewer cases of the swine flu and the death rate compared to the earlier years. In 2011 of 25 patients only one patient died, but in 2009-2010 of 69 patients 7 patients died), which was conditioned by immunity development. The most frequently used regime of lung mechanic ventilation was BIPAR. In the first days antibiotic therapy is not defining. It is necessary to find more effective method of antivirus treatment. PMID:22392781

  13. Baculoviruses modulate a proapoptotic DNA damage response to promote virus multiplication.

    PubMed

    Mitchell, Jonathan K; Friesen, Paul D

    2012-12-01

    The baculovirus Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) initiates apoptosis in diverse insects through events triggered by virus DNA (vDNA) replication. To define the proapoptotic pathway and its role in antivirus defense, we investigated the link between the host's DNA damage response (DDR) and apoptosis. We report here that AcMNPV elicits a DDR in the model insect Drosophila melanogaster. Replication of vDNA activated DDR kinases, as evidenced by ATM-driven phosphorylation of the Drosophila histone H2AX homolog (H2Av), a critical regulator of the DDR. Ablation or inhibition of ATM repressed H2Av phosphorylation and blocked virus-induced apoptosis. The DDR kinase inhibitors caffeine and KU55933 also prevented virus-induced apoptosis in cells derived from the permissive AcMNPV host, Spodoptera frugiperda. This block occurred at a step upstream of virus-mediated depletion of the cellular inhibitor-of-apoptosis protein, an event that initiates apoptosis in Spodoptera and Drosophila. Thus, the DDR is a conserved, proapoptotic response to baculovirus infection. DDR inhibition also repressed vDNA replication and reduced virus yields 100,000-fold, demonstrating that the DDR contributes to virus production, despite its recognized antivirus role. In contrast to virus-induced phosphorylation of Drosophila H2Av, AcMNPV blocked phosphorylation of the Spodoptera H2AX homolog (SfH2AX). Remarkably, AcMNPV also suppressed SfH2AX phosphorylation following pharmacologically induced DNA damage. These findings indicate that AcMNPV alters canonical DDR signaling in permissive cells. We conclude that AcMNPV triggers a proapoptotic DDR that is subsequently modified, presumably to stimulate vDNA replication. Thus, manipulation of the DDR to facilitate multiplication is an evolutionarily conserved strategy among DNA viruses of insects and mammals. PMID:23035220

  14. Antibodies to islet cell autoantigens, rotaviruses and/or enteroviruses in cord blood and healthy mothers in relation to the 20102011 winter viral seasons in Israel: a pilot study

    PubMed Central

    Shulman, L.M.; Hampe, C.S.; Ben-Haroush, A.; Perepliotchikov, Y.; Vaziri-Sani, F.; Israel, S; Miller, K.; Bin, H.; Kaplan, B.; Laron, Z.

    2014-01-01

    Aims To determine whether antivirus and/or islet cell antibodies can be detected in healthy pregnant mothers without diabetes and/or their offspring at birth in two winter viral seasons. Methods Maternal and cord blood sera from 107 healthy pregnant women were tested for islet cell autoantibodies using radioligand binding assays and for anti-rotavirus and anti-CoxB3 antibody using an enzyme-linked immunosorbent assay. Results Glutamic acid decarboxylase (GAD)65 autoantibodies and rotavirus antibodies, present in both maternal and cord blood sera, correlated with an odds ratio of 6.89 (95% CI: 1.0146.78). For five, 22 and 17 pregnancies, antibodies to GAD65, rotavirus and CoxB3, respectively, were detected in cord blood only and not in the corresponding maternal serum. In 10 pregnancies, rotavirus antibody titres in the cord blood exceeded those in the corresponding maternal serum by 2.55-fold. Increased antibody titres after the 20th week of gestation suggested CoxB3 infection in one of the 20 pregnancies and rotavirus in another. Conclusion The concurrent presence of GAD65 antibodies in cord blood and their mothers may indicate autoimmune damage to islet cells during gestation, possibly caused by cross-placental transmission of viral infections and/or antivirus antibodies. Cord blood antibody titres that exceed those of the corresponding maternal sample by >2.5-fold, or antibody-positive cord blood samples with antibody-negative maternal samples, may imply an active in utero immune response by the fetus. PMID:24494628

  15. Does mitogen-induced antibody production by normal blood cells mimic spontaneous production in lupus?

    PubMed

    Dar, O; Salaman, M R; Seifert, M H; Isenberg, D A

    1992-01-01

    Blood cells from patients with systemic lupus erythematosus (SLE) showed a raised level of spontaneous IgG production that included antibodies to DNA and to common environmental antigens (influenza virus haemagglutinin, adenovirus hexon and mannan from Candida albicans). In contrast, no IgG antibody was produced against an antigen not normally encountered in the UK (egg antigen from Schistosoma mansoni) or a self-antigen not generally associated with SLE (thyroglobulin). IgM production was raised to a lesser extent and only antibodies to DNA were detected. When normal cells were stimulated with pokeweed mitogen or S. aureus organisms, the specificity pattern of IgG production was similar to that described above for SLE with the major exception of the absence of IgG anti-DNA. IgM antibodies to DNA and all the other antigens were detected, but the specificity of the IgM ELISA assays for the protein antigens needs further clarification. The activity of IgM anti-DNA relative to total IgM was far greater in the SLE system. These results provide further evidence that a response to self-antigen is required for production of pathogenic IgG autoantibodies in SLE. PMID:1472638

  16. Dermatitis Herpetiformis: A Review of Direct Immunofluorescence Findings.

    PubMed

    Barnadas, Maria A

    2016-04-01

    Direct immunofluorescence (DIF) findings in dermatitis herpetiformis (DH) are incompletely defined. The presence and localization of immune reactants in this disorder are reviewed. A retrospective study on 72 biopsies from 71 patients with DH was performed. Deposits of IgG, IgA, IgM, C'3, C1q, and fibrinogen in skin using a DIF test were analyzed. Granular IgA was observed at the dermal-epidermal junction in 65 biopsies and in the fibers of the papillary dermis in 72 samples. IgG, IgM, C'3, C1q, and fibrinogen were detected in the same locations in lower percentages. IgA was present in the vessels of the papillary dermis in 33 biopsies and in the reticular dermis in 10, followed by fibrinogen, C'3, IgM, and IgG. IgA and IgM were detected in the elastic fibers in 17 and 5 samples, respectively. IgA was observed in 19 cases in the arrector pili muscles, and in a few cases, C'3, IgM, and IgG. IgA and other immune reagents were present in the fibers around hair follicles and in the basement membrane of sweat glands and ducts. Immunofluorescence findings in routine DIF studies from skin biopsies of patients with DH cover a much wider spectrum than previously known. PMID:26630684

  17. Parvovirus B19 infections in state of Rio de Janeiro, Brazil: 526 sera analyzed by IgM-enzyme-linked immunosorbent assay and polymerase chain reaction.

    PubMed

    Mendonça, M C L; Ribeiro, S B; Couceiro, J N S S; von Hubinger, M G

    2005-12-01

    In this study were analyzed 526 sera; the patients aged from two days to 65 years old presenting exanthema, which was the most frequent symptom observed, besides fever, adenomegaly, and arthralgia. These sera were negative by enzyme-linked immunosorbent assay (IgM-ELISA) for either rubella (495), toxoplasma (41), cytomegalovirus (12), measles (40), dengue (56), and they were submitted to nested polymerase chain reaction (PCR) for B19 DNA and commercial IgM-ELISA for B19. In 39 abortion cases, IgM or DNA were not detected, therefore they were not took into account for analysis. Specific DNA and IgM were detected respectively in 71 (14.5%) and IgM in 62 (12.7%) sera from 487 sera analyzed. IgM and DNA were simultaneously detected in 43 (8.8%), while agreement among the results by PCR and IgM-ELISA was observed in 440 (90.4%). The sera were collected from January 1999 to December 2000, most of them in 1999 (325), during winter and spring. The major number of clinical cases was observed in the age group from one to ten years old. IgM or DNA were detected in 23 from 51 municipal districts of the state of Rio de Janeiro, where the samples were collected. PMID:16444415

  18. Deep Chandra observations of HCG 16. II. The development of the intra-group medium in a spiral-rich group

    SciTech Connect

    O'Sullivan, E.; Vrtilek, J. M.; David, L. P.; Zezas, A.; Nulsen, P.; Giacintucci, S.; Ponman, T. J.; Raychaudhury, S.; Mamon, G. A.

    2014-10-01

    We use a combination of deep Chandra X-ray observations and radio continuum imaging to investigate the origin and current state of the intra-group medium (IGM) in the spiral-rich compact group HCG 16. We confirm the presence of a faint (L {sub X,} {sub bolo} = 1.87{sub ?0.66}{sup +1.03}10{sup 41} erg s{sup 1}), low-temperature (0.30{sub ?0.05}{sup +0.07} keV) IGM extending throughout the ACIS-S3 field of view, with a ridge linking the four original group members and extending to the southeast, as suggested by previous ROSAT and XMM-Newton observations. This ridge contains 6.6{sub ?3.3}{sup +3.9} 10{sup 9} M {sub ?} of hot gas and is at least partly coincident with a large-scale H I tidal filament, indicating that the IGM in the inner part of the group is highly multi-phase. We present evidence that the group is not yet virialized, and show that gas has probably been transported from the starburst winds of NGC 838 and NGC 839 into the surrounding IGM. Considering the possible origin of the IGM, we argue that material ejected by galactic winds may have played a significant role, contributing 20%-40% of the observed hot gas in the system.

  19. The evolving intergalactic medium - The uncollapsed baryon fraction in a cold dark matter universe

    NASA Technical Reports Server (NTRS)

    Shapiro, Paul R.; Giroux, Mark L.; Babul, Arif

    1991-01-01

    The time-varying density of the intergalactic medium (IGM) is calculated by coupling detailed numerical calculations of the thermal and ionization balance and radiative transfer in a uniform IGM of H and He to the linearized equations for the growth of density fluctuations in both gases and a dark component in a cold dark matter universe. The IGM density is identified with the collapsed baryon fraction. It is found that even if the IGM is never reheated, a significant fraction of the baryons remain uncollapsed at redshifts of four. If instead the collapsed fraction releases enough ionizing radiation or thermal energy to reionize the IGM by z greater than four as required by the Gunn-Peterson (GP) constraint, the uncollapsed fraction at z of four is even higher. The known quasar distribution is insufficient to supply the ionizing radiation necessary to satisfy the GP constraint in this case and, if stars are instead responsible, a substantial metallicity must have been produced by z of four.

  20. On modeling and measuring the temperature of the z ? 5 intergalactic medium

    SciTech Connect

    Lidz, Adam; Malloy, Matthew

    2014-06-20

    The temperature of the low-density intergalactic medium (IGM) at high redshift is sensitive to the timing and nature of hydrogen and He II reionization, and can be measured from Lyman-alpha (Ly?) forest absorption spectra. Since the memory of intergalactic gas to heating during reionization gradually fades, measurements as close as possible to reionization are desirable. In addition, measuring the IGM temperature at sufficiently high redshifts should help to isolate the effects of hydrogen reionization since He II reionization starts later, at lower redshift. Motivated by this, we model the IGM temperature at z ? 5 using semi-numeric models of patchy reionization. We construct mock Ly? forest spectra from these models and consider their observable implications. We find that the small-scale structure in the Ly? forest is sensitive to the temperature of the IGM even at redshifts where the average absorption in the forest is as high as 90%. We forecast the accuracy at which the z ? 5 IGM temperature can be measured using existing samples of high resolution quasar spectra, and find that interesting constraints are possible. For example, an early reionization model in which reionization ends at z ? 10 should be distinguishableat high statistical significancefrom a lower redshift model where reionization completes at z ? 6. We discuss improvements to our modeling that may be required to robustly interpret future measurements.

  1. Assessment of Urinary Osteopontin in Association with Podocyte for Early Predication of Nephropathy in Diabetic Patients

    PubMed Central

    Al-Malki, Abdulrahman L.

    2014-01-01

    Objectives. Microalbuminuria has been clinically used for noninvasive evaluation of renal dysfunctions. However, it is a nonspecific marker of diabetic nephropathy (DN). Methods. This study was conducted from March 2012 to April 2013 at Biochemistry Unit, King Fahd Medical Research Center (KFMRC). In this study, urinary osteopontin, podocytes number, and levels of immunoglobulin M (IgM) were determined in 60 patients (diabetic normoalbuminuria, diabetic microalbuminuria, and nephritic syndrome) compared with healthy subjects. Results. It was found that in diabetic microalbuminuria patients have a highly significant increase in urinary IgM, osteopontin, and podocyte levels as compared to other groups. Nephrotic syndrome patients showed a moderate significant elevation of these parameters compared to control subjects. At a given specificity of 97%, podocytes yielded the highest sensitivity of all markers, 95.5%. The sensitivity was considerably higher compared to IgM and osteopontin. Podocyte number was positively correlated with serum IgM and osteopontin (r = 0.63 and 0.56), respectively. Its cutoff corresponding to the 10% coefficient of variation was most appropriate for early diagnosis of DN. Conclusion. Monitoring urinary podocyte may provide a noninvasive tool that is a sensitive, accurate, and specific biomarker of glomerular injury and can be used in combination with osteopontin and IgM to more reliably detect and monitor prognosis. PMID:24876663

  2. Specificity of immunoglobulin heavy chain switch correlates with activity of germline heavy chain genes prior to switching.

    PubMed Central

    Stavnezer-Nordgren, J; Sirlin, S

    1986-01-01

    IgM+ cells cultured from the I.29 B cell lymphoma can be induced with lipopolysaccharide (LPS) or, to a greater extent, with LPS plus anti-idiotype antibody to switch to IgG2a, IgE or IgA expression. The isotype switch is accompanied by rearrangement of immunoglobulin (Ig) heavy (H) chain genes. Here we demonstrate that the commitment of the I.29 IgM+ cells to switch to IgA appears to be manifested by hypomethylation of the alpha constant region genes in IgM+ cells, and by the presence of small amounts of RNAs transcribed from non-rearranged alpha gene(s) in IgM+ cells. The commitment to switch to IgE or IgG2a is also in accord with the presence of small amounts of RNA transcripts from the non-rearranged epsilon and gamma 2a genes, although the hypomethylation of the epsilon and gamma 2a genes is not as dramatic as that of the alpha genes. These results suggest that I.29 cells switch specifically to IgA, IgE or IgG2a due to the activation of the corresponding H chain constant region genes in IgM+ cells prior to the actual switch recombination event. Images Fig. 2. Fig. 4. Fig. 5. Fig. 6. PMID:3007121

  3. Non-coordinate expression of J-chain and Blimp-1 define nurse shark plasma cell populations during ontogeny

    PubMed Central

    Castro, Caitlin D.; Ohta, Yuko; Dooley, Helen; Flajnik, Martin F.

    2014-01-01

    Summary Blimp-1 is the master regulator of plasma cell development, controlling genes such as J-chain and secretory Ig heavy chain. However, some mammalian plasma cells do not express J-chain, and mammalian B1 cells secrete natural IgM antibodies without upregulating Blimp-1. While these results have been controversial in mammalian systems, here we describe subsets of normally occurring Blimp-1- antibody secreting cells in nurse sharks, found in lymphoid tissues at all ontogenic stages. Sharks naturally produce large amounts of both pentameric (classically 19S) and monomeric (classically 7S) IgM, the latter an indicator of adaptive immunity. Consistent with the mammalian paradigm, shark Blimp-1 is expressed in splenic 7S IgM-secreting cells, though rarely detected in the J-chain+ cells producing 19S IgM. Although IgM transcript levels are lower in J-chain+ cells, these cells nevertheless secrete 19S IgM in the absence of Blimp-1, as demonstrated by ELISPOT and metabolic labeling. Additionally, cells in the shark bone marrow equivalent (epigonal) are Blimp-1-. Our data suggest that, in sharks, 19S-secreting cells and other secreting memory B cells in the epigonal can be maintained for long periods without Blimp-1, but like in mammals, Blimp-1 is required for terminating the B cell program following an adaptive immune response in the spleen. PMID:23897025

  4. Local immunoglobulin production is different in gastritis associated with dermatitis herpetiformis and simple gastritis.

    PubMed Central

    Valnes, K; Brandtzaeg, P; Elgjo, K; Stave, R; Baklien, K; Fausa, O

    1987-01-01

    The degree of inflammation and atrophy in gastric body mucosal specimens (n = 38) from 28 patients with dermatitis herpetiformis (DH) was graded histologically. Immunoglobulin (Ig) producing cells were enumerated by paired immunofluorescence staining in a 500 microns wide section area from the muscularis mucosae to the lumen (mucosal 'tissue unit'). The number of immunocytes of the three main classes (IgA, IgM, and IgG) was significantly raised with increasing degree of gastritis. All three classes were increased in specimens showing atrophy compared with those without atrophy. IgA cells predominated as in simple gastritis, but a striking difference was a marked increase of IgM cells in specimens with the most pronounced DH-associated gastritis. Relative class distribution of immunocytes within different mucosal zones showed that the percentage of IgA cells was significantly higher in the luminal than in the basal zone, whereas the contrary was true for IgG cells. IgM cells did not show any zonal preference. No relation was seen between small bowel and gastric lesions. The disproportionate increase of gastric IgM producing cells in DH might nevertheless reflect seeding of precursor cells of the secretory immune system generated in the proximal small intestine where the local IgM response is relatively pronounced. PMID:3428685

  5. Inter-Specific coral chimerism: Genetically distinct multicellular structures associated with tissue loss in Montipora capitata

    USGS Publications Warehouse

    Work, T.M.; Forsman, Z.H.; Szabo, Z.; Lewis, T.D.; Aeby, G.S.; Toonen, R.J.

    2011-01-01

    Montipora white syndrome (MWS) results in tissue-loss that is often lethal to Montipora capitata, a major reef building coral that is abundant and dominant in the Hawai'ian Archipelago. Within some MWS-affected colonies in Kane ohe Bay, Oahu, Hawai'i, we saw unusual motile multicellular structures within gastrovascular canals (hereafter referred to as invasive gastrovascular multicellular structure-IGMS) that were associated with thinning and fragmentation of the basal body wall. IGMS were in significantly greater densities in coral fragments manifesting tissue-loss compared to paired normal fragments. Mesenterial filaments from these colonies yielded typical M. capitata mitochondrial haplotypes (CO1, CR), while IGMS from the same colony consistently yielded distinct haplotypes previously only found in a different Montipora species (Montipora flabellata). Protein profiles showed consistent differences between paired mesenterial filaments and IGMS from the same colonies as did seven microsatellite loci that also exhibited an excess of alleles per locus inconsistent with a single diploid organism. We hypothesize that IGMS are a parasitic cellular lineage resulting from the chimeric fusion between M. capitata and M. flabellata larvae followed by morphological reabsorption of M. flabellata and subsequent formation of cell-lineage parasites. We term this disease Montiporaiasis. Although intra-specific chimerism is common in colonial animals, this is the first suspected inter-specific example and the first associated with tissue loss.

  6. Inter-specific coral chimerism: Genetically distinct multicellular structures associated with tissue loss in Montipora capitata

    USGS Publications Warehouse

    Work, Thierry M.; Forsman, Zac H.; Szabo, Zoltan; Lewis, Teresa D.; Aeby, Greta S.; Toonen, Robert J.

    2011-01-01

    Montipora white syndrome (MWS) results in tissue-loss that is often lethal to Montipora capitata, a major reef building coral that is abundant and dominant in the Hawai'ian Archipelago. Within some MWS-affected colonies in Kane'ohe Bay, Oahu, Hawai'i, we saw unusual motile multicellular structures within gastrovascular canals (hereafter referred to as invasive gastrovascular multicellular structure-IGMS) that were associated with thinning and fragmentation of the basal body wall. IGMS were in significantly greater densities in coral fragments manifesting tissue-loss compared to paired normal fragments. Mesenterial filaments from these colonies yielded typical M. capitata mitochondrial haplotypes (CO1, CR), while IGMS from the same colony consistently yielded distinct haplotypes previously only found in a different Montipora species (Montipora flabellata). Protein profiles showed consistent differences between paired mesenterial filaments and IGMS from the same colonies as did seven microsatellite loci that also exhibited an excess of alleles per locus inconsistent with a single diploid organism. We hypothesize that IGMS are a parasitic cellular lineage resulting from the chimeric fusion between M. capitata and M. flabellata larvae followed by morphological reabsorption of M. flabellata and subsequent formation of cell-lineage parasites. We term this disease Montiporaiasis. Although intra-specific chimerism is common in colonial animals, this is the first suspected inter-specific example and the first associated with tissue loss.

  7. Characteristics of natural antibody-secreting cells.

    PubMed

    Savage, Hannah P; Baumgarth, Nicole

    2015-12-01

    Natural IgM plays a critical role in protection from pathogens and the prevention of autoimmunity. While its importance has been shown in many different settings, its origins are incompletely understood. This review focuses on the properties of the natural IgM antibody-secreting cells (ASCs), which arise mainly from the B-1 cell lineage. B-1 cells are generated in multiple waves during development, mostly in the fetal and early postfetal periods. The developmental time points can affect their repertoire: prenatal B-1 cells express a mainly germ line-encoded repertoire, while postnatally developing B-1 cells can express Ig with a greater degree of variation. Spleen and bone marrow, but not the body cavities, are primary sites of natural IgM secretion. Within these tissues heterogeneous populations of IgM ASCs can be found. While some ASCs express classical markers of B-1 lymphocytes, others express those of terminally differentiated plasma cells. A better understanding of the properties of these different natural IgM ASCs could aid their future therapeutic exploitation. PMID:26104151

  8. Serodiagnosis of Scrub Typhus at a Tertiary Care Hospital from Southern India

    PubMed Central

    Roopa, K.S.; Karthika, K.; Sugumar, Madhan; Bammigatti, Chanaveerappa; Shamanna, Suryanarayana Bettadpura

    2015-01-01

    Introduction Scrub typhus, a zoonotic disease is one of the most covert emerging and re-emerging Rickettsial infections. There is an upsurge in the incidence of the disease worldwide with ever-changing habitat. Clinical diagnosis of scrub typhus is challenging as the signs and symptoms of scrub typhus are similar to other febrile illnesses. In developing countries, among the various laboratory tests to diagnose scrub typhus, Weil-Felix test is commonly performed despite its low sensitivity. The Immunofluorescence antibody (IFA) test has its limitations in terms of cost and expertise required. The present study was conducted to determine the seropositivity of IgM ELISA for scrub typhus in clinically suspected cases. Materials and Methods Weil-Felix test and IgM ELISA were performed using clinically suspected cases of scrub typhus using commercially available kits. Results Out of 482 samples tested, 109 were positive by both Weil-Felix test and IgM ELISA. One hundred and sixteen samples which were negative by Weil-Felix test reacted positive by IgM ELISA. Fourteen samples which were positive by Weil-Felix test were negative by ELISA. Conclusion Owing to the limitations of the Weil-Felix test and IFA, commercially available recombinant IgM ELISA which has a good sensitivity and specificity may be an alternative in laboratories with moderate set up. PMID:26675629

  9. Superantigen properties of a human sialoprotein involved in gut-associated immunity.

    PubMed

    Silverman, G J; Roben, P; Bouvet, J P; Sasano, M

    1995-07-01

    Protein Fv (pFv) is a recently described 175-kD gut-associated sialoprotein with a potent capacity for augmentation of antibody-dependent immune functions. To investigate the molecular basis for Fab-mediated binding of pFv, we evaluated a panel of 52 monoclonal IgM and found that approximately 40% bound pFv. Whereas the majority (> or = 75%) of V H3 and V H6 IgM strongly bound pFv, only a small minority (< 20%) of IgM from other V H families bound pFv, and these antibodies had weaker binding interactions. Inhibition studies suggested that all binding occurred at the same (or overlapping) site(s) on pFv. Surface plasmon resonance studies demonstrated binding affinity constants up to 6.7 x 10(8) M-1 for pFv. Biopanning of IgM and IgG Fab phage-display libraries with pFv preferentially selected for V H3 and V H6 antibodies, but also obtained certain V H4 IgM. V H sequence analyses of 36 pFv-binding antibodies revealed that binding did not correlate with CDR sequence, JH, or L chain usage. However, there was preferential selection of pFv binders with V H CDR3 of small size. These studies demonstrate that a protein which enhances immune defense in the gut has structural and functional properties similar to known superantigens. PMID:7615813

  10. Physics of the Intergalactic Medium During the Epoch of Reionization

    NASA Astrophysics Data System (ADS)

    Lidz, Adam

    A major goal of observational and theoretical cosmology is to observe the largely unexplored time period in the history of our universe when the first galaxies form, and to interpret these measurements. Early galaxies dramatically impacted the gas around them in the surrounding intergalactic medium (IGM) by photoionzing the gas during the "Epoch of Reionization" (EoR). This epoch likely spanned an extended stretch in cosmic time: ionized regions formed and grew around early generations of galaxies, gradually filling a larger and larger fraction of the volume of the universe. At some time—thus far uncertain, but within the first billion years or so after the big bang—essentially the entire volume of the universe became filled with ionized gas. The properties of the IGM provide valuable information regarding the formation time and nature of early galaxy populations, and many approaches for studying the first luminous sources are hence based on measurements of the surrounding intergalactic gas. The prospects for improved reionization-era observations of the IGM and early galaxy populations over the next decade are outstanding. Motivated by this, we review the current state of models of the IGM during reionization. We focus on a few key aspects of reionization-era phenomenology and describe: the redshift evolution of the volume-averaged ionization fraction, the properties of the sources and sinks of ionizing photons, along with models describing the spatial variations in the ionization fraction, the ultraviolet radiation field, the temperature of the IGM, and the gas density distribution.

  11. Serological diagnosis of Epstein-Barr virus infection: Problems and solutions

    PubMed Central

    De Paschale, Massimo; Clerici, Pierangelo

    2012-01-01

    Serological tests for antibodies specific for Epstein-Barr virus (EBV) antigens are frequently used to define infection status and for the differential diagnosis of other pathogens responsible for mononucleosis syndrome. Using only three parameters [viral capsid antigen (VCA) IgG, VCA IgM and EBV nuclear antigen (EBNA)-1 IgG],it is normally possible to distinguish acute from past infection: the presence of VCA IgM and VCA IgG without EBNA-1 IgG indicates acute infection, whereas the presence of VCA IgG and EBNA-1 IgG without VCA IgM is typical of past infection. However, serological findings may sometimes be difficult to interpret as VCA IgG can be present without VCA IgM or EBNA-1 IgG in cases of acute or past infection, or all the three parameters may be detected simultaneously in the case of recent infection or during the course of reactivation. A profile of isolated EBNA-1 IgG may also create some doubts. In order to interpret these patterns correctly, it is necessary to determine IgG avidity, identify anti-EBV IgG and IgM antibodies by immunoblotting, and look for heterophile antibodies, anti-EA (D) antibodies or viral genome using molecular biology methods. These tests make it possible to define the status of the infection and solve any problems that may arise in routine laboratory practice. PMID:24175209

  12. Experimental induction of rheumatoid factor-like substances in animal trypanosomiasis

    PubMed Central

    Klein, F.; Mattern, P.; Kornman-v.d. Bosch, Hilda J.

    1970-01-01

    Rheumatoid factor-like substances were induced in rabbits by infection with Trypanosoma equiperdum. There was a certain parallelism with the phenomena described earlier with T. gambiense infections in man. The anti-IgG globulins were IgM with a preference for heterologous (human) IgG in the latex fixation test. A correlation was found between the latex fixation titres and the IgM levels in the sera. A naturally occurring pre-infectious agglutinator was not of IgM nature. The anti-IgG globulins developed in all the infected animals, mostly within 2 weeks and often before the IgG levels in the sera started to increase. The failure to induce rheumatoid factor-like substances in mice infected with a certain strain of T. gambiense indicates the importance of the hostparasite relationship for the formation of rheumatoid factors. The single radial diffusion method according to Mancini, Carbonara & Heremans (1965) did not give valid results for the determination of IgM in the rabbit sera, but could be used for IgG. IgM was determined by an indirect method. These experiments might form the basis of a model for investigating the nature of rheumatoid factor formation. PMID:4992786

  13. Inter-Specific Coral Chimerism: Genetically Distinct Multicellular Structures Associated with Tissue Loss in Montipora capitata

    PubMed Central

    Work, Thierry M.; Forsman, Zac H.; Szabó, Zoltán; Lewis, Teresa D.; Aeby, Greta S.; Toonen, Robert J.

    2011-01-01

    Montipora white syndrome (MWS) results in tissue-loss that is often lethal to Montipora capitata, a major reef building coral that is abundant and dominant in the Hawai'ian Archipelago. Within some MWS-affected colonies in Kane'ohe Bay, Oahu, Hawai'i, we saw unusual motile multicellular structures within gastrovascular canals (hereafter referred to as invasive gastrovascular multicellular structure-IGMS) that were associated with thinning and fragmentation of the basal body wall. IGMS were in significantly greater densities in coral fragments manifesting tissue-loss compared to paired normal fragments. Mesenterial filaments from these colonies yielded typical M. capitata mitochondrial haplotypes (CO1, CR), while IGMS from the same colony consistently yielded distinct haplotypes previously only found in a different Montipora species (Montipora flabellata). Protein profiles showed consistent differences between paired mesenterial filaments and IGMS from the same colonies as did seven microsatellite loci that also exhibited an excess of alleles per locus inconsistent with a single diploid organism. We hypothesize that IGMS are a parasitic cellular lineage resulting from the chimeric fusion between M. capitata and M. flabellata larvae followed by morphological reabsorption of M. flabellata and subsequent formation of cell-lineage parasites. We term this disease Montiporaiasis. Although intra-specific chimerism is common in colonial animals, this is the first suspected inter-specific example and the first associated with tissue loss. PMID:21829541

  14. Improved Diagnosis of Acute Pulmonary Histoplasmosis by Combining Antigen and Antibody Detection

    PubMed Central

    Richer, Sarah M.; Smedema, Melinda L.; Durkin, Michelle M.; Herman, Katie M.; Hage, Chadi A.; Fuller, Deanna; Wheat, L. Joseph

    2016-01-01

    Background. Acute pulmonary histoplasmosis can be severe, especially following heavy inoculum exposure. Rapid diagnosis is critical and often possible by detection of antigen, but this test may be falsely negative in 17% of such cases. Antibody detection by enzyme immunoassay (EIA) may increase sensitivity and permit the measurement of immunoglobulin M (IgM) and immunoglobulin G (IgG) classes of antibodies separately. Methods. Microplates coated with Histoplasma antigen were used for testing of serum from patients with acute pulmonary histoplasmosis and controls in the MVista Histoplasma antibody EIA. Results for IgG and IgM were reported independently. Results. IgG antibodies were detected in 87.5%, IgM antibodies in 67.5%, and IgG and/or IgM antibodies in 88.8% of patients with acute pulmonary histoplasmosis in this assay, while immunodiffusion, complement fixation, and antigen testing showed sensitivities of 55.0%, 73.1%, and 67.5%, respectively (n = 80). Combining antigen and antibody detection increased the sensitivity to 96.3%. Conclusions. The MVista Histoplasma antibody EIA offers increased sensitivity over current antibody tests while also allowing separate detection of IgG and IgM antibodies and complementing antigen detection. Combining antigen and EIA antibody testing provides an optimal method for diagnosis of acute pulmonary histoplasmosis. PMID:26797210

  15. Association of anti phosphatidyl ethanolamine antibodies and low complement levels in systemic sclerosis patients--results of a cross-sectional study.

    PubMed

    B?l?nescu, Paul; L?daru, Anca; B?l?nescu, Eugenia; B?icu?, Cristian; Dan, Gheorghe Andrei

    2015-10-01

    Some systemic sclerosis (Ssc) patients express antiphospholipid antibodies and their percentage varies within studies in the literature. The particular role of these antibodies in clinical manifestations of Ssc is still unknown. The aim of the study was to examine an extended panel of antiphospholipid antibodies in Ssc patients who did not have any clinical features of antiphospholipid antibody syndrome. A cross-sectional study was designed and 36 consecutive patients with Ssc were recruited. A relatively high proportion of patients (14 patients - 38.9%) had antiphospholipid antibody presence. Most Ssc patients (11 patients - 30.6%) had IgM anti phosphatidyl ethanolamine antibodies. Serum IgM anti phosphatidyl ethanolamine antibodies, IgM anti prothrombin and IgG anti ?2 glycoprotein 1 antibodies were associated with low complement levels in Ssc patients. In multivariate analysis, only serum IgM anti phosphatidyl ethanolamine antibodies concentration and serum IgG anti ?2 glycoprotein 1 antibodies concentration were independently associated with hypocomplementemia after adjusting for age and gender. No other correlations with Ssc clinical characteristics were found. In conclusion, antiphospholipid antibodies are present in a large proportion of Ssc patients who do not have clinical features or a history of antiphospholipid antibodies. IgM anti phosphatidyl ethanolamine antibodies seem to be more frequent and the dominant antiphospholipid antibody type in the group recruited from the Romanian Ssc population. PMID:26067612

  16. Evaluation of a rapid enzyme immunoassay system for serologic diagnosis of Mycoplasma pneumoniae infection.

    PubMed

    Fedorko, D P; Emery, D D; Franklin, S M; Congdon, D D

    1995-11-01

    A 5-min qualitative membrane enzyme-linked immunoassay (EIA) from Remel (Mycoplasma pneumoniae immunoglobulin G (IgG)/IgM Antibody Test System) was evaluated for its ability to detect IgM and IgG at levels indicating active or recent infection. Specimens from 131 patients were evaluated using an immunofluorescent antibody assay (IFA) to determine IgG and IgM titers and the membrane EIA. An enzyme-linked immunosorbent assay (ELISA) performed by a reference laboratory was used for discrepancy resolution. There were 34 IgM positive specimens (titer > or = 1:16), 19 IgG positive specimens (titer > or = 1:64), and 78 negative specimens. Compared with IFA and/or ELISA, the membrane EIA was 97% sensitive for the detection of IgM and 79% sensitive for the detection of IgG. Of the 78 specimens called negative, 17 specimens had IgG titers< or = 1:32) or an ELISA result indicating prior exposure, and the membrane EIA called seven of 17 (41%) positive. For the detection of both IgG and IgM, the membrane EIA had a sensitivity of 91%, specificity of 91%, and positive and negative predictive values of 87 and 93%, respectively. The Remel membrane EIA is a rapid and reliable assay for the diagnosis of active or recent M. pneumoniae respiratory tract infections. PMID:8849651

  17. Development of an Enzyme-Linked Immunosorbent Assay for Immunoglobulin M Antibodies against Measles Virus

    PubMed Central

    Roodbari, F.; Roustai, M. H.; Mostafaie, A.; Soleimanjdahi, H.; Foroshani, R. Sarrami; Sabahi, F.

    2003-01-01

    Measles is a highly contagious respiratory virus infection, with typical clinical symptoms including maculopapular rash, fever, cough, coryza, and conjunctivitis. Despite implementation of widespread vaccination programs throughout the world, the rates of global morbidity and mortality are still considerable. This study was performed to design a reliable indirect enzyme-linked immunosorbent assay (ELISA) to measure measles-specific immunoglobulin M (IgM). First, human IgM was purified, and then an anti-IgM antibody was produced in rabbits and purified in a multistep process. The rabbit IgG against human IgM was conjugated with peroxidase. Measles virus-infected Vero cells produced viral antigen. One hundred serum samples from infants of 9 to 18 months of age, mostly vaccinated, were evaluated for determining the presence of specific IgM antibodies against measles virus. The samples were also evaluated for neutralizing antibodies against measles virus by a microneutralization test (MNT). By comparing the results of the ELISA with those of MNT, it was demonstrated that ELISA had a sensitivity and specificity of 100 and 92%, respectively. On the other hand, when the results obtained by our ELISA system were compared with those of an imported measles virus IgM ELISA kit (EIAgen; Adaltis Italia SPa, Bologna, Italy), a high level of agreement was shown (k = 0.926). PMID:12738645

  18. Comparison of Major Immunoglobulins Intrathecal Synthesis Patterns in Ecuadorian and Cuban Patients with Angiostrongyliasis

    PubMed Central

    Padilla-Docal, Brbara; Dorta-Contreras, Alberto J.; Moreira, Juan M.; Martini-Robles, Luiggi; Muzzio-Aroca, Jenny; Alarcn, Fernando; Magraner-Tarrau, Mara Esther; Bu-Coifiu-Fanego, Raisa

    2011-01-01

    Angiostrongylus cantonensis meningitis was first reported in Cuba in 1981, and it was recently reported in South America. The aim of this paper is to evaluate the intrathecal immunoglobulin synthesis patterns from Cuba's and Ecuador's patients with angiostrongyliasis; 8 Ecuadorian patients from two different outbreaks and 28 Cuban patients were studied. Simultaneous blood and cerebrospinal fluid simples were taken. Immunoglobulin (Ig) A, IgM, IgG, and albumin were quantified by radial immunodiffusion. Corresponding Reibergrams were applied. A three-Ig pattern was the most frequent in the two groups, but IgM was presented in all Ecuadorian young mature patients; however, in the Cuban children, only 12 of 28 patients had intrathecal IgM, but about 90% had an IgA and IgG synthesis at time of later puncture. This indicates that, with a larger amount of parasites ingested, clinical symptoms are more severe, and a higher frequency of intrathecal IgM synthesis could be observed. This is discussed as a similarity with the intrathecal IgM synthesis in African trypanosomiasis. PMID:21363978

  19. Significance of a Positive Toxoplasma Immunoglobulin M Test Result in the United States.

    PubMed

    Dhakal, Reshika; Gajurel, Kiran; Pomares, Christelle; Talucod, Jeanne; Press, Cynthia J; Montoya, Jose G

    2015-11-01

    A positive Toxoplasma immunoglobulin M (IgM) result is often interpreted as a marker of an acute infection. However, IgM can persist for several years, and Toxoplasma commercial IgM diagnostic test kits can yield a number of false-positive results. For these reasons, a chronic Toxoplasma infection can be erroneously classified as an acute infection, resulting in serious adverse consequences, especially in pregnant women, leading to emotional distress and unnecessary interventions, including termination of pregnancy. Interpretation of Toxoplasma serology at a reference laboratory can help differentiate a recently acquired infection from a chronic infection. Serological test results for 451 patients with positive Toxoplasma IgM and IgG test results obtained at nonreference laboratories (NRLs) that were referred to Palo Alto Medical Foundation Toxoplasma Serology Laboratory (PAMF-TSL) to determine whether the patient was acutely or chronically infected were retrospectively reviewed. PAMF-TSL results established that of the 451 patients, 335 (74%) had a chronic infection, 100 (22%) had an acute infection, and 7 (2%) were not infected, and for 9 (2%), results were indeterminate. Positive Toxoplasma IgM and IgG test results obtained at NRLs cannot accurately distinguish between acute and chronic infections. To do so, testing at reference laboratories is required, as mandated in 1997 in a letter from the Food and Drug Administration (FDA) to clinicians and laboratories in the United States. PMID:26354818

  20. Immunoglobulin M seropositivity for Toscana virus in a random population sample in Sicily

    PubMed Central

    Amodio, Emanuele; Cusi, Maria Grazia; Valenti, Rosalia Maria; Valentini, Melissa; Mammina, Caterina; Gori-Savellini, Gianni; Vitale, Francesco; Romano, Nino; Goedert, James J.; Calamusa, Giuseppe

    2013-01-01

    SUMMARY Objectives High Toscana virus (TOSV) antibody seropositivity rates have been documented in the last decade, especially in the Mediterranean area. It is unclear if these rates are associated with a recent or past exposure to the virus. This is of importance, as primary infection can cause neurologic complications, especially in adults. The aim of the present study was to assess the current active TOSV circulation in western Sicily. Methods A cross-sectional seroprevalence study was conducted on 271 individuals aged 492 years, sampled from the general population of a small city. Each participant completed a self-administered questionnaire and provided serum, which was analyzed for the presence of specific anti-TOSV IgM and IgG. Results Anti-TOSV IgM was detected in eight (3.0%) participants, of whom only three had anti-TOSV IgG. The prevalence of anti-TOSV IgM was highest in subjects aged 2534 and 3544 years (7.1% and 4.8%, respectively). All subjects positive for anti-TOSV IgM were resident in the suburban area. Conclusions The detection of IgM documented the circulation of TOSV, a Phlebovirus, in a random population sample of Sicilian adults. The highest risk of TOSV seroconversion in subjects living in the suburbs appears to suggest a high density of TOSV vectors in peri-urban areas. PMID:22726418

  1. Evaluation of a dot ELISA kit for measuring immunoglobulin M antibodies to canine parvovirus and distemper virus.

    PubMed

    Waner, T; Mazar, S; Nachmias, E; Keren-Kornblatt, E; Harrus, S

    2003-05-10

    A dot ELISA for the detection of immunoglobulin M (IgM) antibodies to canine distemper virus (CDC) and canine parvovirus (CPV) was assessed. The titres of IgM antibodies to CDV and CPV in 100 dogs were measured by the Immunocomb ELISA kit and compared with the results derived from the immunofluorescence assay (IFA). There was a strong correlation between the results of the dot ELISA technique and the IFA (P < 0.001). The dot ELISA kit was also used to assess the changes in the levels of immunoglobulin G (IgG) and IgM antibodies to CPV and CDV in 10 puppies vaccinated with a polyvalent vaccine. High levels of IgM antibodies to CPV were first detected seven days after they were vaccinated, and after nine days all the pups had high titres of IgG antibodies to CPV. High levels of IgM antibodies to CDV were detected after nine days and the highest average titres were recorded after 12 days. IgG antibodies to CDV were present from nine days after vaccination. PMID:12762487

  2. Development and evaluation of rapid point-of-care tests for detection of Enterovirus 71 and Coxsackievirus A16 specific immunoglublin M antibodies.

    PubMed

    Zhang, Jing; Weng, Zuxing; Du, Hailian; Xu, Feihai; He, Shuizhen; He, Delei; Cheng, Tong; Zhang, Jun; Ge, Shengxiang; Xia, Ningshao

    2016-05-01

    Two colloidal gold immunochromatographic assays (CGIAs) for detection of EV71- and CA16- immunoglobulin M (IgM) were developed and evaluated. A total of 1465 sera collected from children with hand, foot, and mouth disease (HFMD), non-HFMD patients and healthy children. The sensitivity of IgM CGIA tests for EV71 and CA16 were 97.6% (330/338) and 91.6% (296/323) respectively, compared to those who were viral RNA positive by PCR. Their performances were comparable to those of commercial ELISA kits, with agreement of 98.1% for EV71-IgM and 97.3% for CA16-IgM. In addition, for EV71- and CA16-IgM CGIAs, the results of whole blood samples were 99.6% (248/249) and 100% (191/191) concordant to those with serum samples, respectively. As rapid point-of-care (POC) tests, the two CGIAs were suitable to be used in community clinic units, especially in resource-poor areas and will facilitate the control of HFMD. PMID:26912234

  3. Monoclonal immunoglobulin M antibody to Japanese encephalitis virus that can react with a nuclear antigen in mammalian cells.

    PubMed Central

    Gould, E A; Chanas, A C; Buckley, A; Clegg, C S

    1983-01-01

    An immunoglobulin M (IgM) class monoclonal antibody raised against Japanese encephalitis virus reacted with an epitope on the nonstructural virus protein P74 (NV4 in the old nomenclature) of several flaviviruses and also with an antigen present in the nuclei of a variety of mammalian cell types. This antigen had a characteristic granular distribution by immunofluorescence and may correspond to a polypeptide of molecular weight 56,000 seen in nitrocellulose transfers of sodium dodecyl sulfate-polyacrylamide gels. Cross-reactivity with nuclear antigen was also occasionally observed in the IgM antibody fraction of mice early after infection with Japanese encephalitis virus and also in acute sera from some clinical cases of encephalitis containing IgM antibody to Japanese encephalitis virus. Images PMID:6135665

  4. Immunoglobulin production by coeliac biopsies in organ culture.

    PubMed Central

    Wood, G M; Shires, S; Howdle, P D; Losowsky, M S

    1986-01-01

    The production of immunoglobulins by jejunal mucosa during organ culture has been studied. In 18 untreated coeliac patients the amounts of IgA, secretory IgA and IgM in the culture medium were higher than in those from 17 normal controls. The results in 15 treated coeliac patients did not differ from the control subjects. Mucosal biopsies from patients with serum IgA deficiency produced very little IgA, but large amounts of IgG and IgM. The addition of neither Frazer's gluten fraction III, nor alpha-gliadin to the culture system stimulated any additional increased secretion of immunoglobulins from the untreated coeliac patients. Production of IgA and IgM by the small bowel mucosa continues during organ culture, but that of IgG appears insignificant. PMID:3781327

  5. Evolution of the intergalactic medium - What happened during the epoch z = 3-10?

    NASA Technical Reports Server (NTRS)

    Ikeuchi, S.; Ostriker, J. P.

    1986-01-01

    An attempt is made to model consistently the thermal and dynamic history of the intergalactic medium (IGM) from the era of reheating (z = 10-5) to the present, and to provide a unified explanation for the origin of ordinary galaxies, blue compact objects, and Lyman-alpha clouds. The evolution of the intergalactic gas is analyzed, treating the IGM as perfectly homogeneous at every epoch and taking into account radiative and Compton cooling, adiabatic cooling, shock heating, and heating produced by the diffuse UV flux. It is suggested that the IGM must have been heated to higher than a 10 to the 6th K by shock heasting caused either by explosions of pregalactic objects or expanding voids. The formation of intergalactic clouds by fragmentation of the resulting shells and the subsequent collapse of the shells to form galaxies are studied. An attempt is made to determine model parameters on the basis of an analysis of Lyman-alpha absorption lines.

  6. Plasma Effects on Extragalactic Ultrahigh-energy Cosmic-Ray Hadron Beams in Cosmic Voids II. Kinetic Instability of Parallel Electrostatic Waves

    NASA Astrophysics Data System (ADS)

    Krakau, S.; Schlickeiser, R.

    2016-02-01

    The linear instability of an ultrarelativistic hadron beam in the unmagnetized intergalactic medium (IGM) is investigated with respect to the excitation of parallel electrostatic and electromagnetic fluctuations. This analysis is important for the propagation of extragalactic ultrarelativistic cosmic rays from their distant sources to Earth. As opposed to the previous paper, we calculate the minimum instability growth time for Lorentz-distributed cosmic rays which traverse the hot IGM. The growth times are orders of magnitude higher than the cosmic-ray propagation time in the IGM. Since the backreaction of the generated plasma fluctuations (plateauing) lasts longer than the propagation time, the cosmic-ray hadron beam can propagate to the Earth without losing a significant amount of energy to electrostatic turbulence.

  7. Cosmic Reionization On Computers III. The Clumping Factor

    DOE PAGESBeta

    Kaurov, Alexander A.; Gnedin, Nickolay Y.

    2015-09-09

    We use fully self-consistent numerical simulations of cosmic reionization, completed under the Cosmic Reionization On Computers project, to explore how well the recombinations in the ionized intergalactic medium (IGM) can be quantified by the effective "clumping factor." The density distribution in the simulations (and, presumably, in a real universe) is highly inhomogeneous and more-or-less smoothly varying in space. However, even in highly complex and dynamic environments, the concept of the IGM remains reasonably well-defined; the largest ambiguity comes from the unvirialized regions around galaxies that are over-ionized by the local enhancement in the radiation field ("proximity zones"). This ambiguity precludesmore » computing the IGM clumping factor to better than about 20%. Furthermore, we discuss a "local clumping factor," defined over a particular spatial scale, and quantify its scatter on a given scale and its variation as a function of scale.« less

  8. Detection of immunoglobulin M in cerebrospinal fluid from syphilis patients by enzyme-linked immunosorbent assay.

    PubMed Central

    Lee, J B; Farshy, C E; Hunter, E F; Hambie, E A; Wobig, G H; Larsen, S A

    1986-01-01

    Cerebrospinal fluid (CSF) samples were evaluated in an immunoglobulin M enzyme-linked immunosorbent assay (IgM ELISA) for syphilis with sonic extracts of Treponema pallidum coated on polystyrene plates. The ELISA procedure was reproducible, and T. pallidum antigens were stable., A total of 15 CSF samples from patients with neurosyphilis, 18 CSF samples from patients with syphilis, 12 CSF samples from patients treated for syphilis, and 494 CSF samples from patients with neurologic or other systemic diseases were tested. The IgM ELISA gave reactive results in all of six symptomatic and congenital neurosyphilitic patients and none of nine asymptomatic neurosyphilitic patients. Of 524 CSF samples from nonneurosyphilitic individuals, 513 were nonreactive, resulting in 98% test specificity. The IgM ELISA in CSF should prove to be useful for confirmation of symptomatic neurosyphilis. PMID:3533984

  9. Further Evaluation of a Rapid Diagnostic Test for Melioidosis in an Area of Endemicity

    PubMed Central

    O'Brien, Mathew; Freeman, Kevin; Lum, Gary; Cheng, Allen C.; Jacups, Susan P.; Currie, Bart J.

    2004-01-01

    Immunochromatographic test (ICT) kits for the rapid detection of immunoglobulin G (IgG) and IgM antibodies to Burkholderia pseudomallei were compared to the indirect hemagglutination (IHA) assay. In 138 culture-confirmed melioidosis cases, sensitivities were 80, 77, and 88% for IHA, ICT IgG, and ICT IgM, respectively. In a prospective study of 160 consecutive sera samples sent for melioidosis serology, respective specificities were 91, 90, and 69, positive predictive values were 41, 32, and 18, and negative predictive values were 99, 98, and 100%. ICT IgM kits are unreliable for diagnosis of melioidosis, but ICT IgG kits may be useful for diagnosing travelers presenting with possible melioidosis who return from regions where melioidosis is endemic. PMID:15131200

  10. Comparison of PCR, culture, and serological tests for diagnosis of Mycoplasma pneumoniae respiratory tract infection in children.

    PubMed

    Dorigo-Zetsma, J W; Zaat, S A; Wertheim-van Dillen, P M; Spanjaard, L; Rijntjes, J; van Waveren, G; Jensen, J S; Angulo, A F; Dankert, J

    1999-01-01

    For diagnosis of Mycoplasma pneumoniae infection we compared two rapid tests, PCR and the immunoglobulin M immunofluorescence assay (IgM IFA), with culture and the complement fixation test (CFT), in a prospective study among 92 children with respiratory tract infection and 74 controls. Based on positivity of culture and/or CFT as the diagnostic criterion, nine patients (10%) were diagnosed with M. pneumoniae infection. All patients positive by culture were also positive by PCR. In all controls cultures, PCRs, and serological assays were negative, except in one with a positive IgM IFA. The IgM IFA had a low positive predictive value of 50%. Only a combination of PCR (seven patients) and CFT (seven patients) allowed diagnosis of all cases. PMID:9854056

  11. Cosmic Reionization On Computers III. The Clumping Factor

    SciTech Connect

    Kaurov, Alexander A.; Gnedin, Nickolay Y.

    2015-09-09

    We use fully self-consistent numerical simulations of cosmic reionization, completed under the Cosmic Reionization On Computers project, to explore how well the recombinations in the ionized intergalactic medium (IGM) can be quantified by the effective "clumping factor." The density distribution in the simulations (and, presumably, in a real universe) is highly inhomogeneous and more-or-less smoothly varying in space. However, even in highly complex and dynamic environments, the concept of the IGM remains reasonably well-defined; the largest ambiguity comes from the unvirialized regions around galaxies that are over-ionized by the local enhancement in the radiation field ("proximity zones"). This ambiguity precludes computing the IGM clumping factor to better than about 20%. Furthermore, we discuss a "local clumping factor," defined over a particular spatial scale, and quantify its scatter on a given scale and its variation as a function of scale.

  12. Evaluation of five commercial tests for detection of immunoglobulin M antibodies to human parvovirus B19.

    PubMed

    Bruu, A L; Nordb, S A

    1995-05-01

    The following commercial tests for detection of immunoglobulin M antibodies to human parvovirus B19 were evaluated: Ideia Parvovirus B19-IgM, MRL Diagnostics Human Parvovirus B19 IgM ELISA, Parvoscan-B19, and Biotrin Parvo B19 IgM EIA and IF. A total of 203 serum specimens from patients who probably have current B19 infections or have other viral infections and sera with rheumatoid factor were investigated. Between 75 and 79 of 102 serum samples from patients thought to have current B19 infections yielded positive results with the different tests. Ideia had the highest specificity (94.8%), while Parvoscan showed a specificity of only 70.1%. Our evaluation results show that Ideia, MRL, and Biotrin EIA and IF can be recommended for diagnostic purposes. PMID:7615755

  13. Fc receptors of rat peritoneal macrophages: immunoglobulin class specificity and sensitivity to drugs affecting the microfilament or microtubule system.

    PubMed Central

    Medgyesi, G A; Fris, G; Dezs, B; Gergely, J; Bazin, H

    1980-01-01

    Macrophage-cytophilic antibody activity of various immunoglobulin classes and subclasses was tested in two different rosetting systems. Cytophilic antibody activity of IgM, IgG2a and IgG1 was verified in the SRBC system, while IgM, IgG2a and IgG2c were found to be active in the trypanosome system. Sensitivity to cytochalasin B treatment of SRBC rosette formation was dependent on the class of antibody and decreased in the following order: IgM > IgG1 > IgG2a. Trypanosome rosette formation was prevented by the same drug regardless the type of antibody. Vinblastin caused an enhancement of rosette formation in the SRBC system in low concentration, except when the antibody belonged to subclass IgG1. The enhancing effect was less pronounced in the trypanosome system. Images Figure 1 PMID:7191828

  14. Cosmic Reionization on Computers. III. The Clumping Factor

    NASA Astrophysics Data System (ADS)

    Kaurov, Alexander A.; Gnedin, Nickolay Y.

    2015-09-01

    We use fully self-consistent numerical simulations of cosmic reionization, completed under the Cosmic Reionization On Computers project, to explore how well the recombinations in the ionized intergalactic medium (IGM) can be quantified by the effective clumping factor. The density distribution in the simulations (and, presumably, in a real universe) is highly inhomogeneous and more-or-less smoothly varying in space. However, even in highly complex and dynamic environments, the concept of the IGM remains reasonably well-defined; the largest ambiguity comes from the unvirialized regions around galaxies that are over-ionized by the local enhancement in the radiation field (proximity zones). That ambiguity precludes computing the IGM clumping factor to better than about 20%. We also discuss a local clumping factor, defined over a particular spatial scale, and quantify its scatter on a given scale and its variation as a function of scale.

  15. Endothelial dysfunction plays a key role in increasing cardiovascular risk in type 2 diabetes: the Hoorn study.

    PubMed

    van Sloten, Thomas T; Henry, Ronald M A; Dekker, Jacqueline M; Nijpels, Giel; Unger, Thomas; Schram, Miranda T; Stehouwer, Coen D A

    2014-12-01

    In the pathogenesis of cardiovascular events, interaction between risk factors has seldom been identified. However, endothelial dysfunction on the one hand and type 2 diabetes mellitus, impaired glucose metabolism (IGM), and insulin resistance on the other may act synergistically (ie, interact) in the development of cardiovascular disease. We therefore investigated the interaction between endothelial dysfunction and type 2 diabetes mellitus, IGM, and insulin resistance with regard to risk of cardiovascular events. In a prospective population-based cohort (n=445; 69 years; 55% women; 23% type 2 diabetes mellitus, 28% IGM [by design]), endothelial dysfunction (brachial artery flow-mediated dilatation), glucose tolerance (oral glucose tolerance test), and insulin sensitivity (homeostasis model assessment for insulin resistance [HOMA2-IR]) were determined. After a median follow-up of 7.6 years, 106 participants had had a cardiovascular event. After adjustments, 1 SD less flow-mediated dilatation was associated with cardiovascular events in type 2 diabetes mellitus (hazard ratio 1.69 [95% confidence interval, 1.14-2.52]) and IGM (1.50 [0.95-2.37]) and among those in the highest HOMA2-IR tertile (1.92 [1.42-2.60]), but not in normal glucose metabolism (0.85 [0.63-1.16]) or among those in the lower 2 HOMA2-IR tertiles combined (0.85 [0.65-1.12]). Interaction between flow-mediated dilatation and type 2 diabetes mellitus, IGM, or insulin resistance was present on an additive (relative excess risk caused by interaction>0) and on a multiplicative scale (P interaction<0.05). Endothelial dysfunction and type 2 diabetes mellitus, IGM, or insulin resistance synergistically increase cardiovascular event risk. This identifies endothelial dysfunction as a key therapeutic target in these individuals. PMID:25225211

  16. Child Mortality Estimation 2013: An Overview of Updates in Estimation Methods by the United Nations Inter-Agency Group for Child Mortality Estimation

    PubMed Central

    Alkema, Leontine; New, Jin Rou; Pedersen, Jon; You, Danzhen

    2014-01-01

    Background In September 2013, the United Nations Inter-agency Group for Child Mortality Estimation (UN IGME) published an update of the estimates of the under-five mortality rate (U5MR) and under-five deaths for all countries. Compared to the UN IGME estimates published in 2012, updated data inputs and a new method for estimating the U5MR were used. Methods We summarize the new U5MR estimation method, which is a Bayesian B-spline Bias-reduction model, and highlight differences with the previously used method. Differences in UN IGME U5MR estimates as published in 2012 and those published in 2013 are presented and decomposed into differences due to the updated database and differences due to the new estimation method to explain and motivate changes in estimates. Findings Compared to the previously used method, the new UN IGME estimation method is based on a different trend fitting method that can track (recent) changes in U5MR more closely. The new method provides U5MR estimates that account for data quality issues. Resulting differences in U5MR point estimates between the UN IGME 2012 and 2013 publications are small for the majority of countries but greater than 10 deaths per 1,000 live births for 33 countries in 2011 and 19 countries in 1990. These differences can be explained by the updated database used, the curve fitting method as well as accounting for data quality issues. Changes in the number of deaths were less than 10% on the global level and for the majority of MDG regions. Conclusions The 2013 UN IGME estimates provide the most recent assessment of levels and trends in U5MR based on all available data and an improved estimation method that allows for closer-to-real-time monitoring of changes in the U5MR and takes account of data quality issues. PMID:25013954

  17. Quantitative radiommunoassay for DNA-binding antibodies. [Iodine 131, Iodine 125

    SciTech Connect

    Smith, L.H.; Guyer, R.L.; Minami, R.M.; Teplitz, R.L.

    1981-09-01

    A radioimmunoassay (RIA) is described for the measurement of serum immunoglobulins capable of binding to double-standard or single-standard DNA. DNA attached to Sephadex G-50 by ultraviolet radiation was used as a solid- phase immunoabsorbent for DNA-binding proteins from serum. Goat anti-human (GAH) IgG (/sup 125/I-labeled) were used to detect the human immunoglobulins bound onto the washed DNA-Sephadex. The quantities of immunoglobulins bound were determined by comparison with a standard curve constructed by dilution of a plasma from an systemic lupus erythematosus (SLE) patient containing known amounts of bound, DNA-specific IgM and IgG. Another RIA was employed for measuring levels of IgG and IgM. In combination with measurements of the total serum IgM and IgG, the RIA allowed for the determination of the fraction of the total serum IgM or IgG that was specific for double- or single-standard DNA. For a pool of normal human sera the quantities were as follows: 0.04% of the total IgM and 0.001% of the total IgG bound double-standard DNA; 0.22% of the total IgM and 0.05% of the total IgG bound single-stranded DNA. This capability is important because information regarding the quantitative measurement of antibodies to DNA and their class determination may be of significance in monitoring the status of subjects with SLE.

  18. Rearrangements and deletions of immunoglobulin heavy chain genes in the double-producing B cell lymphoma I.29.

    PubMed Central

    Stavnezer, J; Marcu, K B; Sirlin, S; Alhadeff, B; Hammerling, U

    1982-01-01

    The B cell lymphoma I.29 consists of a mixture of cells expressing membrane-bound immunoglobulin M (IgM) (lambda) and IgA (lambda) of identical idiotypes. Whereas most of the cells express either IgM or IgA alone, 1 to 5% of the cells in this tumor express IgM and IgA simultaneously within the cytoplasm and on the cell membrane (R. Sitia et al., J. Immunol. 127:1388-1394, 1981; R. Sitia, unpublished data). When IgM+ cells are purified from the lymphoma and passaged in mice or cultured, a portion of the cells convert to IgA+. These properties suggest that some cells of the I.29 lymphoma may undergo immunoglobulin heavy chain switching, although it is also possible that the mixed population was derived by a prior switching event in a clone of cells. We performed Southern blotting experiments on genomic DNAs isolated from populations of I.29 cells containing variable proportions of IgM+ and IgA+ cells and on a number of cell lines derived from the lymphoma. The results were consistent with the deletion model for heavy chain switching, as the IgM+ cells contained rearranged mu genes and alpha genes in the germ line configuration on both the expressed and nonexpressed heavy chain chromosomes, whereas the IgA+ cells had deleted both mu genes and contained one rearranged and one germ line alpha gene. In addition, segments of DNA located within the intervening sequence 5' to the mu gene, near the site of switch recombination, were deleted from both the expressed and the nonexpressed chromosomes. Although mu genes were deleted from both chromosomes in the IgA+ cells, the sites of DNA recombination differed on the two chromosomes. On the expressed chromosome, Smu sequences were recombined with S alpha sequences, whereas on the nonexpressed chromosome, Smu sequences were recombined with S gamma 3 sequences. Images PMID:6290869

  19. An evolutionarily conserved program of B-cell development and activation in zebrafish

    PubMed Central

    Wittamer, Valerie; Bertrand, Julien Y.; Lewis, Kanako L.; Pratt, David N.; Delgado, Noemi; Schale, Sarah E.; McGue, Caitlyn; Jacobsen, Bradley H.; Doty, Alyssa; Pao, Yvonne; Yang, Hongbo; Chi, Neil C.; Magor, Brad G.; Traver, David

    2013-01-01

    Teleost fish are among the most ancient vertebrates possessing an adaptive immune system with B and T lymphocytes that produce memory responses to pathogens. Most bony fish, however, have only 2 types of B lymphocytes, in contrast to the 4 types available to mammals. To better understand the evolution of adaptive immunity, we generated transgenic zebrafish in which the major immunoglobulin M (IgM+) B-cell subset expresses green fluorescence protein (GFP) (IgM1:eGFP). We discovered that the earliest IgM+ B cells appear between the dorsal aorta and posterior cardinal vein and also in the kidney around 20 days postfertilization. We also examined B-cell ontogeny in adult IgM1:eGFP;rag2:DsRed animals, where we defined pro-B, pre-B, and immature/mature B cells in the adult kidney. Sites of B-cell development that shift between the embryo and adult have previously been described in birds and mammals. Our results suggest that this developmental shift occurs in all jawed vertebrates. Finally, we used IgM1:eGFP and cd45DsRed;blimp1:eGFP zebrafish to characterize plasma B cells and investigate B-cell function. The IgM1:eGFP reporter fish are the first nonmammalian B-cell reporter animals to be described. They will be important for further investigation of immune cell evolution and development and host-pathogen interactions in zebrafish. PMID:23861249

  20. The Lyman β forest as a cosmic thermometer

    SciTech Connect

    Iršič, Vid; Viel, Matteo E-mail: viel@oats.inaf.it

    2014-12-01

    We present a comprehensive analysis of high resolution hydrodynamic simulations in terms of Lyman α and Lyman β one dimensional flux power spectra P{sub αα} and P{sub ββ}). In particular, we focus on the behaviour that the flux auto-power spectra and cross-power spectra P{sub αβ}) display when the intergalactic medium (IGM) thermal history is changed in a range of values that bracket a reference model, while cosmological parameters are kept fixed to best fit the cosmic microwave background data. We present empirical fits that describe at the sub-percent level the dependence of the power spectra on the thermal parameters. At the largest scales, the power spectra show a constant bias between each other that is set by the parameters describing the IGM thermal state. The cross-power spectrum has an oscillatory pattern and crosses zero at a scale which depends on T{sub 0}, the IGM temperature at the mean density, for reasonable values of the power-law index γ of the IGM temperature-density relation T=T{sub 0}(1+δ){sup γ-1}). By performing a Fisher matrix analysis, we find that the power spectrum P{sub ββ} is more sensitive to the thermal history than P{sub αα} alone, due to the fact that it probes denser regions than Lyman α. When we combine the power and cross spectra the constraints on γ can be improved by a factor ∼ 4, while the constraints on T{sub 0} improve by a factor of ∼ 2. We address the role of signal-to-noise and resolution by mocking realistic observations and we conclude that the framework presented in this work can significantly improve the knowledge of the IGM thermal state, which will in turn guarantee better constraints on IGM-derived cosmological parameters.

  1. Heating the intergalactic medium by X-rays from population III binaries in high-redshift galaxies

    SciTech Connect

    Xu, Hao; Norman, Michael L.; Ahn, Kyungjin; Wise, John H.; O'Shea, Brian W. E-mail: mlnorman@ucsd.edu E-mail: jwise@gatech.edu

    2014-08-20

    Due to their long mean free path, X-rays are expected to have an important impact on cosmic reionization by heating and ionizing the intergalactic medium (IGM) on large scales, especially after simulations have suggested that Population III (Pop III) stars may form in pairs at redshifts as high as 20-30. We use the Pop III distribution and evolution from a self-consistent cosmological radiation hydrodynamic simulation of the formation of the first galaxies and a simple Pop III X-ray binary model to estimate their X-ray output in a high-density region larger than 100 comoving (Mpc){sup 3}. We then combine three different methods—ray tracing, a one-zone model, and X-ray background modeling—to investigate the X-ray propagation, intensity distribution, and long-term effects on the IGM thermal and ionization state. The efficiency and morphology of photoheating and photoionization are dependent on the photon energies. The sub-kiloelectronvolt X-rays only impact the IGM near the sources, while the kiloelectronvolt photons contribute significantly to the X-ray background and heat and ionize the IGM smoothly. The X-rays just below 1 keV are most efficient in heating and ionizing the IGM. We find that the IGM might be heated to over 100 K by z = 10 and the high-density source region might reach 10{sup 4} K, limited by atomic hydrogen cooling. This may be important for predicting the 21 cm neutral hydrogen signals. On the other hand, the free electrons from X-ray ionizations are not enough to contribute significantly to the optical depth of the cosmic microwave background to the Thomson scattering.

  2. Comparison of the Sensitivity of Laboratory Diagnostic Methods from a Well-Characterized Outbreak of Mumps in New York City in 2009

    PubMed Central

    Rosen, Jennifer B.; Doll, Margaret K.; McNall, Rebecca J.; McGrew, Marcia; Williams, Nobia; Lopareva, Elena N.; Barskey, Albert E.; Punsalang, Amado; Rota, Paul A.; Oleszko, William R.; Hickman, Carole J.; Zimmerman, Christopher M.; Bellini, William J.

    2013-01-01

    A mumps outbreak in upstate New York in 2009 at a summer camp for Orthodox Jewish boys spread into Orthodox Jewish communities in the Northeast, including New York City. The availability of epidemiologic information, including vaccination records and parotitis onset dates, allowed an enhanced analysis of laboratory methods for mumps testing. Serum and buccal swab samples were collected from 296 confirmed cases with onsets from September through December 2009. All samples were tested using the Centers for Disease Control and Prevention (CDC) capture IgM enzyme immunoassay (EIA) and a real-time reverse transcription-PCR (rRT-PCR) that targets the short hydrophobic gene. A subset of the samples (n = 205) was used to evaluate 3 commercial mumps IgM assays and to assess the sensitivity of using an alternative target gene (nucleoprotein) in the rRT-PCR protocol. Among 115 cases of mumps with 2 documented doses of measles, mumps, and rubella (MMR) vaccine, the CDC capture IgM EIA detected IgM in 51% of serum samples compared to 9% to 24% using three commercial IgM assays. The rRT-PCR that targeted the nucleoprotein gene increased RNA detection by 14% compared to that obtained with the original protocol. The ability to detect IgM improved when serum was collected 3 days or more after symptom onset, whereas sensitivity of RNA detection by rRT-PCR declined when buccal swabs were collected later than 2 days after onset. Selection of testing methods and timing of sample collection are important factors in the ability to confirm infection among vaccinated persons. These results reinforce the need to use virus detection assays in addition to serologic tests. PMID:23324519

  3. Administration in vivo of recombinant interleukin 2 protects mice against septic death.

    PubMed Central

    Weyand, C; Goronzy, J; Fathman, C G; O'Hanley, P

    1987-01-01

    Administration in vivo of recombinant interleukin 2 (rIL-2) to mice induces a polyclonal IgM response. When co-administered with a specific antigen, rIL-2 can enhance concentrations of murine IgM antibodies specific for the antigen by fivefold within 7 d of initial treatment. IgM antibodies that are induced after injection of rIL-2 include antibodies specific for J5, a cell wall core lipopolysaccharide (LPS) antigen that is shared by the different members of the Enterobactericeae family. We report here that mice pretreated with rIL-2 or immunized with J5 antigen 7 d before bacterial challenge were protected from septic death that is caused by intraperitoneal challenges with Escherichia coli. Optimal protection was provided by a combined J5 antigen and rIL-2 treatment. Acquisition of the rIL-2 and J5 antigen-induced protection against lethal bacterial infection coincided temporally with maximal serum IgM titers that also contained IgM antibodies specific for the J5 antigen. In passive immunization experiments, the affinity-purified IgM fraction in sera of rIL-2-treated animals was identified as necessary and sufficient for protection. The IgM-depleted serum had no protective effect. The nonspecific augmentation of host-defense mechanisms without the induction of endotoxin manifestations makes rIL-2 a potential candidate to any alternative LPS-containing vaccines for the prevention of bacterial infections by gram-negative organisms since the core LPS antigen is shared among gram-negative bacteria. PMID:3294901

  4. First Colombian Multicentric Newborn Screening for Congenital Toxoplasmosis

    PubMed Central

    Gómez-Marin, Jorge Enrique; de-la-Torre, Alejandra; Angel-Muller, Edith; Rubio, Jorge; Arenas, Jaime; Osorio, Elkin; Nuñez, Lilian; Pinzon, Lyda; Mendez-Cordoba, Luis Carlos; Bustos, Agustin; de-la-Hoz, Isabel; Silva, Pedro; Beltran, Monica; Chacon, Leonor; Marrugo, Martha; Manjarres, Cristina; Baquero, Hernando; Lora, Fabiana; Torres, Elizabeth; Zuluaga, Oscar Elias; Estrada, Monica; Moscote, Lacides; Silva, Myriam Teresa; Rivera, Raul; Molina, Angie; Najera, Shirley; Sanabria, Antonio; Ramirez, Maria Luisa; Alarcon, Claudia; Restrepo, Natalia; Falla, Alejandra; Rodriguez, Tailandia; Castaño, Giovanny

    2011-01-01

    Aims To determine the incidence of congenital toxoplasmosis in Colombian newborns from 19 hospital or maternal child health services from seven different cities of five natural geographic regions (Caribbean, Central, Andean, Amazonia and Eastern). Materials and Methods We collected 15,333 samples from umbilical cord blood between the period of March 2009 to May 2010 in 19 different hospitals and maternal-child health services from seven different cities. We applied an IgM ELISA assay (Vircell, Spain) to determine the frequency of IgM anti Toxoplasma. The results in blood cord samples were confirmed either by western blot and repeated ELISA IgM assay. In a sub-sample of 1,613 children that were negative by the anti-Toxoplasma IgM assay, the frequency of specific anti-Toxoplasma IgA by the ISAGA assay was determined. All children with positive samples by IgM, IgA, clinical diagnosis or treatment during pregnancy were recalled for confirmatory tests after day 10 of life. Results 61 positive samples for specific IgM (0.39%) and 9 positives for IgA (0.5%) were found. 143 questionnaires were positive for a clinical diagnosis or treatment for toxoplasmosis during pregnancy. 109 out of the 218 children that had some of the criteria for postnatal confirmatory tests were followed. Congenital toxoplasmosis infection was confirmed in 15 children: 7 were symptomatic, and three of them died before the first month of life (20% of lethality). A significant correlation was found between a high incidence of markers for congenital toxoplasmosis and higher mean annual rainfall for the city. Conclusions Incidence for congenital toxoplasmosis is significantly different between hospitals or maternal child health services from different cities in Colombia. Mean annual rainfall was correlated with incidence of congenital toxoplasmosis. PMID:21655304

  5. Characterization of Markers of the Progression of Human Parvovirus B19 Infection in Virus DNA-Positive Plasma Samples

    PubMed Central

    Bonjoch, Xavier; Obispo, Francesc; Alemany, Cristina; Pacha, Ana; Rodrguez, Esteban; Xair, Dolors

    2015-01-01

    Summary Background Accurate characterization of the infection stage in parvovirus B19(B19V)-positive plasma donations would help establish the donation deferral period to contribute to a safe fractionation pool of plasma. Methods Viral DNA load of 74 B19V DNA-positive plasma samples from whole blood donations was determined by titration using nucleic acid testing. Markers of cellular (neopterin) and humoral (B19V-specific IgM and IgG) immune response were determined by ELISA in 32 B19V DNA-positive samples and in 13 B19V DNA-negative samples. The infection progression profile was estimated according to B19V DNA load and the presence of immune response markers. Results B19V DNA load in the 74 samples was 106-1013 IU/ml. The distribution of 14 out of 32 selected B19V DNA-positive samples plus 2 B19V DNA-negative samples with no immune response marker followed along an upward curve according to B19V DNA load. After the peak, the distribution of 18 immune marker-positive samples followed along a downward curve according to their B19V DNA load and was grouped as follows: neopterin (n = 4), neopterin+ IgM (n = 8), neopterin + IgM + IgG (n = 3), IgM + IgG (n = 2), IgM (n = 1). There were 11 B19V DNA-negative IgG-positive samples. Conclusion This study of B19V-DNA load and levels of neopterin, IgM, and IgG allows for reliable characterization and distribution into the different stages of B19V infection. PMID:26557815

  6. Efficient Immunoglobulin Gene Disruption and Targeted Replacement in Rabbit Using Zinc Finger Nucleases

    PubMed Central

    Offner, Sonja; Ros, Francesca; Lifke, Valeria; Zeitler, Bryan; Rottmann, Oswald; Vincent, Anna; Zhang, Lei; Jenkins, Shirin; Niersbach, Helmut; Kind, Alexander J.; Gregory, Philip D.; Schnieke, Angelika E.; Platzer, Josef

    2011-01-01

    Rabbits are widely used in biomedical research, yet techniques for their precise genetic modification are lacking. We demonstrate that zinc finger nucleases (ZFNs) introduced into fertilized oocytes can inactivate a chosen gene by mutagenesis and also mediate precise homologous recombination with a DNA gene-targeting vector to achieve the first gene knockout and targeted sequence replacement in rabbits. Two ZFN pairs were designed that target the rabbit immunoglobulin M (IgM) locus within exons 1 and 2. ZFN mRNAs were microinjected into pronuclear stage fertilized oocytes. Founder animals carrying distinct mutated IgM alleles were identified and bred to produce offspring. Functional knockout of the immunoglobulin heavy chain locus was confirmed by serum IgM and IgG deficiency and lack of IgM+ and IgG+ B lymphocytes. We then tested whether ZFN expression would enable efficient targeted sequence replacement in rabbit oocytes. ZFN mRNA was co-injected with a linear DNA vector designed to replace exon 1 of the IgM locus with ∼1.9 kb of novel sequence. Double strand break induced targeted replacement occurred in up to 17% of embryos and in 18% of fetuses analyzed. Two major goals have been achieved. First, inactivation of the endogenous IgM locus, which is an essential step for the production of therapeutic human polyclonal antibodies in the rabbit. Second, establishing efficient targeted gene manipulation and homologous recombination in a refractory animal species. ZFN mediated genetic engineering in the rabbit and other mammals opens new avenues of experimentation in immunology and many other research fields. PMID:21695153

  7. Bovine natural antibodies in antibody-dependent bactericidal activity against Escherichia coli and Salmonella Typhimurium and risk of mastitis.

    PubMed

    van Altena, S E C; Peen, M A; van der Linden, F H; Parmentier, H K; Savelkoul, H F J; Tijhaar, E J

    2016-03-01

    Natural antibodies (NAbs) are mostly IgM antibodies produced without antigenic stimulation and serve as a first line of defence of the immune system. As both natural and specific antibodies are present in animals, NAbs are studied by determining the IgM response to naïve antigens like keyhole limpet hemocyanin (KLH). In this study, we selected cows based on high and low anti-KLH IgM titers, reflecting high and low NAb titers, and determined if the anti-KLH IgM titers were indicative for the recognition of common microbial structures (lipopolysaccharide, lipoteichoic acid and peptidoglycan) and intact bacteria (Escherichia coli and Salmonella Typhimurium). Sera with high NAbs titers showed more IgM and IgG binding to common microbial structures and S. Typhimurium bacteria than sera with low NAbs titers. The same association was observed for IgM binding to E. coli, but not for IgG binding to E. coli. Antibody-mediated complement killing of E. coli and S. Typhimurium in a newly developed bactericidal test was equal between high and low NAb cows. However, relating the outcome of the bactericidal test to the development of mastitis within one and even four years after sampling showed a significant negative correlation implying cows that were less potent in bacterial killing had a higher chance on developing mastitis. In conclusion, sera with high NAbs titers had more antibodies binding to common microbial structures and intact bacteria. Furthermore, the bactericidal test might provide a useful prognostic tool for the development of mastitis. PMID:26964714

  8. The immunoglobulin M response to rubella vaccine in young adult women.

    PubMed Central

    Mortimer, P. P.; Edwards, J. M.; Porter, A. D.; Tedder, R. S.; Haslehurst, J.

    1984-01-01

    Rubella vaccination histories were taken from 333 young women working in the head office of a retail organization: 29% said they had had vaccine and 47% said they had not. The remainder did not know. Forty-six per cent of those less than or equal to 25 years old (who should have been offered vaccine at school), and 6% of those greater than 25 years old, said they had been vaccinated. When screened for immunity to rubella by radial haemolysis (RH) 3% had a low level of antibody (less than 15 i.u./ml) and 11% had no antibody. After immunization with Cendevax the specific rubella IgM response was measured by an IgM antibody capture radioimmunassay (MACRIA). It was only detectable in the group without RH antibody, and was present in 26/31 of them. The IgM response to Cendevax was strongest in specimens taken 20-39 days after immunization, but in 10 out of 11 cases tested was still present at around 71 days. The specific IgM responses to Cendevax were very similar to those in women given Almevax in an earlier study, when measured in parallel tests. Taking both vaccines together, specific IgM was present in 35 out of 36 vaccinees without pre-existing antibody tested between 40 and 77 days post-immunization. Detection of specific IgM by MACRIA would therefore be an effective means of determining susceptibility retrospectively in rubella vaccinees found to be pregnant. PMID:6376624

  9. The Lyman ? forest as a cosmic thermometer

    NASA Astrophysics Data System (ADS)

    Iri?, Vid; Viel, Matteo

    2014-12-01

    We present a comprehensive analysis of high resolution hydrodynamic simulations in terms of Lyman ? and Lyman ? one dimensional flux power spectra P?? and P??). In particular, we focus on the behaviour that the flux auto-power spectra and cross-power spectra P??) display when the intergalactic medium (IGM) thermal history is changed in a range of values that bracket a reference model, while cosmological parameters are kept fixed to best fit the cosmic microwave background data. We present empirical fits that describe at the sub-percent level the dependence of the power spectra on the thermal parameters. At the largest scales, the power spectra show a constant bias between each other that is set by the parameters describing the IGM thermal state. The cross-power spectrum has an oscillatory pattern and crosses zero at a scale which depends on T0, the IGM temperature at the mean density, for reasonable values of the power-law index ? of the IGM temperature-density relation T=T0(1+?)?-1). By performing a Fisher matrix analysis, we find that the power spectrum P?? is more sensitive to the thermal history than P?? alone, due to the fact that it probes denser regions than Lyman ?. When we combine the power and cross spectra the constraints on ? can be improved by a factor ~ 4, while the constraints on T0 improve by a factor of ~ 2. We address the role of signal-to-noise and resolution by mocking realistic observations and we conclude that the framework presented in this work can significantly improve the knowledge of the IGM thermal state, which will in turn guarantee better constraints on IGM-derived cosmological parameters.

  10. High-precision analyses of Lyα damping wing of gamma-ray bursts in the reionization era: On the controversial results from GRB 130606A at z = 5.91

    NASA Astrophysics Data System (ADS)

    Totani, Tomonori; Aoki, Kentaro; Hattori, Takashi; Kawai, Nobuyuki

    2016-02-01

    The unprecedentedly bright afterglow of Swift GRB 130606A at z = 5.91 gave us a unique opportunity to probe the reionization era through high-precision analyses of the redward damping wing of Lyα absorption, but the reported constraints on the neutral hydrogen fraction (f_{H I}) in intergalactic medium (IGM) derived from spectra taken by different telescopes are in contradiction to each other. Here we examine the origin of this discrepancy by analyzing the spectrum taken by the Very Large Telescope (VLT) with our own analysis code previously used to fit the Subaru spectrum. Though the VLT team reported no evidence for IGM H I using the VLT spectrum, we confirm our previous result of preferring non-zero IGM H I (the best fit f_{H I} ˜ 0.06, when IGM H I extends to the GRB redshift). The fit residuals of the VLT spectrum using the model without IGM H I show the same systematic trend as the Subaru spectrum. We consider that the likely origin of the discrepancy between the two teams is the difference of the wavelength ranges adopted in the fittings; our wavelength range is wider than that of the VLT team, and also we avoided the shortest wavelength range of deep Lyα absorption (λobs < 8426 Å), because this region is dominated by H I in the host galaxy and the systematic uncertainty about host H I velocity distribution is large. We also study the sensitivity of these results to the adopted Lyα cross-section formulae, ranging from the classical Lorentzian func