Dataset Information

Competition between serum IgG, IgM, and IgA anti-glycan antibodies.

ABSTRACT: Anti-glycan antibodies are an abundant subpopulation of serum antibodies with critical functions in many immune processes. Changes in the levels of these antibodies can occur with the onset of disease, exposure to pathogens, or vaccination. As a result, there has been significant interest in exploiting anti-glycan antibodies as biomarkers for many diseases. Serum contains a mixture of anti-glycan antibodies that can recognize the same antigen, and competition for binding can potentially influence the detection of antibody subpopulations that are more relevant to disease processes. The most abundant antibody isotypes in serum are IgG, IgM, and IgA, but little is known regarding how these different isotypes compete for the same glycan antigen. In this study, we developed a multiplexed glycan microarray assay and applied it to evaluate how different isotypes of anti-glycan antibodies (IgA, IgG, and IgM) compete for printed glycan antigens. While IgG and IgA antibodies typically outcompete IgM for peptide or protein antigens, we found that IgM outcompete IgG and IgA for many glycan antigens. To illustrate the importance of this effect, we provide evidence that IgM competition can account for the unexpected observation that IgG of certain antigen specificities appear to be preferentially transported from mothers to fetuses. We demonstrate that IgM in maternal sera compete with IgG resulting in lower than expected IgG signals. Since cord blood contains very low levels of IgM, competition only affects maternal IgG signals, making it appear as though certain IgG antibodies are higher in cord blood than matched maternal blood. Taken together, the results highlight the importance of competition for studies involving anti-glycan antibodies.

SUBMITTER: Muthana SM

PROVIDER: S-EPMC4373866 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Competition between serum IgG, IgM, and IgA anti-glycan antibodies.

Muthana Saddam M SM Xia Li L Campbell Christopher T CT Zhang Yalong Y Gildersleeve Jeffrey C JC

PloS one 20150325 3

Anti-glycan antibodies are an abundant subpopulation of serum antibodies with critical functions in many immune processes. Changes in the levels of these antibodies can occur with the onset of disease, exposure to pathogens, or vaccination. As a result, there has been significant interest in exploiting anti-glycan antibodies as biomarkers for many diseases. Serum contains a mixture of anti-glycan antibodies that can recognize the same antigen, and competition for binding can potentially influenc ...[more]

PMID: 25807519

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Project description:IntroductionWe and others have previously shown that antibodies against cyclic citrullinated proteins (anti-CCP) precede the development of rheumatoid arthritis (RA) and in a more recent study we reported that individuals who subsequently developed RA had increased concentrations of several cytokines and chemokines years before the onset of symptoms of joint disease. Here we aimed to evaluate the prevalence and predictive values of anti-CCP antibodies of IgG, IgM and IgA isotype in individuals who subsequently developed RA and also to relate these to cytokines and chemokines, smoking, genetic factors and radiographic score.MethodsA case-control study (1:4 ratio) was nested within the Medical Biobank and the Maternity cohorts of Northern Sweden. Patients with RA were identified from blood donors predating the onset of disease by years. Matched controls were selected randomly from the same registers. IgG, IgA and IgM anti-CCP2 antibodies were determined using EliA anti-CCP assay on ImmunoCAP 250 (Phadia AB, Uppsala, Sweden).ResultsOf 86 patients with RA identified as blood donors prior to the onset of symptoms, samples were available from 71 for analyses. The median (Q1 to Q3) predating time was 2.5 years (1.1 to 5.9 years). The sensitivity of anti-CCP antibodies in the pre-patient samples was 35.2% for IgG, 23.9% for IgA, and 11.8% for IgM. The presence of IgG and IgA anti-CCP antibodies was highly significant compared with controls. IgG and IgA anti-CCP2 predicted RA significantly in conditional logistic regression models odds ratio (OR) = 94.1, 95% confidence interval (CI) 12.7 to 695.4 and OR = 11.1, 95% CI 4.4 to 28.1, respectively, the IgM anti-CCP showed borderline significance OR = 2.5 95% CI 0.9 to 6.3. Concentrations of all anti-CCP isotypes increased the closer to the onset of symptoms the samples were collected with an earlier and higher increase for IgG and IgA compared with IgM anti-CCP. IgA and IgG anti-CCP positive individuals had different patterns of up-regulated chemokines and also, smoking brought forward the appearance of IgA anti-CCP antibodies in pre-RA individuals.ConclusionsAnti-CCP2 antibodies of both the IgG and IgA isotypes pre-dated the onset of RA by years; also, both IgG and IgA anti-CCP2 antibodies predicted the development of RA, with the highest predictive value for IgG anti-CCP2 antibodies.

Project description:BackgroundChronic pulmonary aspergillosis (CPA) is an underdiagnosed and misdiagnosed disease and now increasingly recognised. However, the diagnosis of CPA remains challenging. In this study, we aimed to investigate the diagnostic values of serum Aspergillus-specific IgG, IgA and IgM antibodies in patients with CPA.MethodsThe prospective study was performed at Chinese People's Liberation Army General Hospital in Beijing, from January 2017 to December 2017. Adult patients with lung lesions presented as cavity, nodule, mass, bronchiectasis or severe fibrotic destruction with at least two lobes in CT imaging were enrolled. One hundred healthy persons were also enrolled as additional controls. The serum levels of Aspergillus-specific IgG, IgA and IgM antibodies and galactomannan (GM) levels were measured simultaneously by plate ELISA kit.ResultsA total of 202 patients were enrolled in this study, including 42 CPA patients, 60 non-CPA patients and 100 healthy persons. The most common underlying lung diseases in CPA patients were bronchiectasis (28.6%) and COPD (19.0%). The most common symptoms in the CPA patients were cough (76.2%), sputum (71.4%), and fever (45.2%); chest pain (4.8%) was infrequent. Receiver operating characteristic (ROC) curve analysis revealed that the optimal CPA diagnostic cut-off of Aspergillus-specific IgG, IgA and IgM assays and GM test were 89.3 AU/mL, 8.2 U/mL, 73.3 AU/mL and 0.5μg/L, respectively. The serum levels of Aspergillus-specific IgG and IgA in CPA patients were higher than these in non-CPA patients or healthy persons. The sensitivities and specificities of Aspergillus-specific IgG, IgA, IgM tests and GM test were 78.6 and 94.4%, 64.3 and 89.4%, 50.0 and 53.7% and 71.4 and 58.1%, respectively.ConclusionsThe sensitivity and specificity of serum Aspergillus-specific IgG assay are satisfactory for diagnosing CPA, while the performance of Aspergillus-specific IgA assay is moderate. Aspergillus-specific IgM assay and serum GM test have limited value for CPA diagnosis.Trial registrationNCT03027089 . Registered 20 January 2017.

Dataset Information

Competition between serum IgG, IgM, and IgA anti-glycan antibodies.

Publications

Competition between serum IgG, IgM, and IgA anti-glycan antibodies.

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