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Autoantibodies are abundant in all human sera: a demographic characterization via protein microarrays

ABSTRACT: Human serum samples were probed onto human protein microarrays in order to ascertain the number and diversity of naturally ocurring self-reactive IgG autoantibodies. In the study presented here, 166 human serum samples were probed onto human protein microarrays in order to identify self-reactive IgG autoantibodies and study their number and diversity in variable donor demographics. Microarray data were analyzed using several statistical programs, including Prospector v5.2, and autoantibodies with a relative fluorescence Z-factor value of greater than or equal to 0.4 were considered significant.

ORGANISM(S): Homo sapiens

SUBMITTER: Robert Nagele

PROVIDER: E-GEOD-39087 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Natural IgG autoantibodies are abundant and ubiquitous in human sera, and their number is influenced by age, gender, and disease.

Nagele Eric P EP Han Min M Han Min M Acharya Nimish K NK DeMarshall Cassandra C Kosciuk Mary C MC Nagele Robert G RG

PloS one 20130402 4

The presence of self-reactive IgG autoantibodies in human sera is largely thought to represent a breakdown in central tolerance and is typically regarded as a harbinger of autoimmune pathology. In the present study, immune-response profiling of human serum from 166 individuals via human protein microarrays demonstrates that IgG autoantibodies are abundant in all human serum, usually numbering in the thousands. These IgG autoantibodies bind to human antigens from organs and tissues all over the b ...[more]

PMID: 23589757

Similar Datasets

Autoantibodies are abundant in all human sera: a demographic characterization via protein microarrays

Project description:Human serum samples were probed onto human protein microarrays in order to ascertain the number and diversity of naturally ocurring self-reactive IgG autoantibodies.

2013-04-25 | GSE39087 | GEO

Diagnosis of Parkinson's Disease Based on Disease-Specific Autoantibody Profiles

Project description:Parkinson's Disease (PD) and Non-Demented Control (NDC) human sera were probed onto human protein microarrays in order to identify differentially expressed autoantibody biomarkers that could be used as diagnostic indicators. In the study presented here, 29 PD and 40 NDC human serum samples were probed onto human protein microarrays in order to identify differentially expressed autoantibodies. Microarray data was analyzed using several statistical significance algorithms, and autoantibodies that demonstrated significant group prevelance were selected as biomarkers of disease. Prediction classification analysis tested the diagnostic efficacy of the identified biomarkers; and differentiation of PD samples from other neurodegeneratively-diseased and non-neurodegeneratively-diseased controls (Alzheimer's disease, multiple sclerosis, and breast cancer) confirmed their specificity.

2012-02-27 | E-GEOD-29654 | biostudies-arrayexpress

Diagnosis of Alzheimer's Disease Based on Disease-Specific Autoantibody Profiles

Project description:Alzheimer's Disease (AD) and Non-Demented Control (NDC) human sera were probed onto human protein microarrays in order to identify differentially expressed autoantibody biomarkers that could be used as diagnostic indicators. In the study presented here, 50 AD and 40 NDC human serum samples were probed onto human protein microarrays in order to identify differentially expressed autoantibodies. Microarray data was analyzed using several statistical significance algorithms, and autoantibodies that demonstrated significant group prevelance were selected as biomarkers of disease. Prediction classification analysis tested the diagnostic efficacy of the identified biomarkers; and differentiation of AD samples from other neurodegeneratively-diseased and non-neurodegeneratively-diseased controls (Parkinson's disease and breast cancer, respectively) confirmed their specificity.

2011-07-12 | E-GEOD-29676 | biostudies-arrayexpress

Broad spectrum antibodies to self-antigens and cytokines in RAG deficiency

Project description:Overall, this work describes the largest cohort of patients with RAG mutations and an associated phenotype consisting of combined immunodeficiency and granulomatous lesions and/or autoimmunity (CID-G/AI). By using multiple methods (microarray, ELISA and multiplex bead technology), we have consistently identified a distinctive signature of anti-cytokine antibodies in patients with RAG-dependent immunodeficiencies, especially in those with CID-G/AI and a history of severe viral infections. These autoantibodies were not detected in a large panel of patients with other forms of primary immunodeficiency, and may therefore represent a novel biomarker panel of this condition. Known autoantigens, cytokines, chemokines, growth factors and receptors were printed onto microarrays. All targets were printed in triplicate. Arrays were probed with diluted plasma and autoantibodies were detected with a AF647 conjugated anti-human IgG secondary.

2015-07-08 | E-GEOD-70618 | biostudies-arrayexpress

Protein microarray (Protoarray, Invitrogen) screening with APECED patient, healthy relative and healthy control serum samples

Project description:APECED is a monogenic autoimmune disease caused by defects in Autoimmune Regulator (AIRE) gene that promotes the expression of self-antigens in the thymus. The autoimmune phenotype in APECED is variable, and multiple proteins are targeted by autoantibodies. This study used human protein arrays to screen autoantibody targets in APECED and to identify novel autoimmune targets. Altogether 100 sera samples from 82 individual APECED patients were profiled using Protoarray antibody specificity service at Invitrogen as well as samples from 12 healthy controls and 8 healthy relatives. The protein arrays (ProtoArray v5.1) were probed as described in Invitrogenâs protocol for Immune Response BioMarker Profiling using detection reagent (Alexa Fluor 647 Goat Anti-Human IgG A21445, Invitrogen) and blocking buffer (Blocking Buffer Kit PA055, Invitrogen). Arrays were scanned using a GenePix 4000B fluorescent scanner, and the data was acquired with GenePixÂ® Pro software. The arrays were probed with sera at a dilution of 1:500.

2017-10-01 | E-MTAB-5369 | biostudies-arrayexpress

Serum and Tear Autoantibodies from NOD and NOR Mice as Potential Diagnostic Indicators of Local and Systemic Inflammation in Sjögren's Disease [MCF_SSK_546]

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2025-01-28 | GSE286504 | GEO

Human cerebrospinal fluid autoantibody lipid microarray profiling (Fig. 2A)

Project description:Lipids comprise 70% of the myelin sheath, and autoantibodies against lipids may contribute to the demyelination that characterizes multiple sclerosis (MS). We used lipid antigen microarrays and lipid mass spectrometry to identify bona fide lipid targets of the autoimmune response in MS brain and an animal model of MS to explore the role of the identified lipids in autoimmune demyelination. We found that autoantibodies in MS target a phosphate group in phosphatidylserine and oxidized phosphatidylcholine derivatives. Administration of these lipids ameliorated experimental autoimmune encephalomyelitis by suppressing activation and inducing apoptosis of autoreactive T cells, effects mediated by the lipids' saturated fatty-acid side chains. Thus, phospholipids represent a natural anti-inflammatory class of compounds that have potential as novel therapeutics for MS. Fig. 2A. Mini-Array I: IgG antibody reactivity to various glycero-3-phosphocholine lipids in CSF samples from patients with relapsing remitting MS and from control patients with other neurological disease. Lipid hits with the lowest FDR (q=0.029) were clustered according to their reactivity profiles. 47 different lipids were custom-spotted in duplicate using the CAMAG Automatic TLC Sampler (ATS4) robot to spray 200 nl of 10 to 100 pmol of lipids onto PVDF membranes affixed to the surface of microscope slides. The slides were probed with cerebrospinal fluid (CSF) from 24 human patient samples. 25 slides total: 13 relapsing-remitting MS, 11 other neurological disease, and 1 secondary Ab alone (not included in this submission). CSF diluted 1/20. HRP-conjugated secondary Ab (goat anti-human IgM/IgG) diluted 1/175. ECL for 3 minutes.

2012-05-08 | E-GEOD-37670 | biostudies-arrayexpress

Human cerebrospinal fluid autoantibody lipid microarray profiling (Fig. 1A)

Project description:Lipids comprise 70% of the myelin sheath, and autoantibodies against lipids may contribute to the demyelination that characterizes multiple sclerosis (MS). We used lipid antigen microarrays and lipid mass spectrometry to identify bona fide lipid targets of the autoimmune response in MS brain and an animal model of MS to explore the role of the identified lipids in autoimmune demyelination. We found that autoantibodies in MS target a phosphate group in phosphatidylserine and oxidized phosphatidylcholine derivatives. Administration of these lipids ameliorated experimental autoimmune encephalomyelitis by suppressing activation and inducing apoptosis of autoreactive T cells, effects mediated by the lipids' saturated fatty-acid side chains. Thus, phospholipids represent a natural anti-inflammatory class of compounds that have potential as novel therapeutics for MS. Fig. 1A. Lipid-array profiling of IgG+IgM antibody reactivity in cerebrospinal fluid (CSF) samples from MS patients (relapsing remitting MS; secondary progressive MS; primary progressive MS), healthy controls, and other neurological disease controls. Lipid hits with the lowest FDR (q=0.048) were clustered according to their reactivity profiles. 48 different lipids were custom-spotted in duplicate using the CAMAG Automatic TLC Sampler (ATS4) robot to spray 200 nl of 10 to 100 pmol of lipids onto PVDF membranes affixed to the surface of microscope slides. The slides were probed with cerebrospinal fluid (CSF) from 59 human patient samples. 60 slides total: 18 relapsing-remitting MS, 14 secondary-progressive MS, 1 primary-progressive MS, 21 other neurological disease, 5 healthy control, 1 secondary Ab alone (not included in this submission). CSF diluted 1/10. HRP-conjugated secondary Ab (goat anti-human IgM/IgG) diluted 1/8000. ECL for 3 minutes.

2012-05-08 | E-GEOD-37664 | biostudies-arrayexpress

Human cerebrospinal fluid autoantibody lipid microarray profiling (Fig. 2C)

Project description:Lipids comprise 70% of the myelin sheath, and autoantibodies against lipids may contribute to the demyelination that characterizes multiple sclerosis (MS). We used lipid antigen microarrays and lipid mass spectrometry to identify bona fide lipid targets of the autoimmune response in MS brain and an animal model of MS to explore the role of the identified lipids in autoimmune demyelination. We found that autoantibodies in MS target a phosphate group in phosphatidylserine and oxidized phosphatidylcholine derivatives. Administration of these lipids ameliorated experimental autoimmune encephalomyelitis by suppressing activation and inducing apoptosis of autoreactive T cells, effects mediated by the lipids' saturated fatty-acid side chains. Thus, phospholipids represent a natural anti-inflammatory class of compounds that have potential as novel therapeutics for MS. Fig. 2C. Mini-Array II: IgG antibody reactivity to lipids constituting polar head-group and side-chain modifications of PGPC in CSF samples from relapsing remitting MS patients and other neurological disease controls. Lipid hits with the lowest FDR (q=0.016) were clustered according to their reactivity profiles. 19 different lipids were custom-spotted in duplicate using the CAMAG Automatic TLC Sampler (ATS4) robot to spray 200 nl of 10 to 100 pmol of lipids onto PVDF membranes affixed to the surface of microscope slides. The slides were probed with cerebrospinal fluid (CSF) from 26 human patient samples. 27 slides total: 12 relapsing-remitting MS, 13 other neurological disease, 1 healthy control (not included in this submission), and 1 secondary Ab alone (not included in this submission). CSF diluted 1/20. HRP-conjugated secondary Ab (donkey anti-human IgG) diluted 1/8000. ECL for 3 minutes.

2012-05-08 | E-GEOD-37826 | biostudies-arrayexpress

Clonal landscape of autoantibody-secreting plasmablasts in COVID-19 patients

Project description:Although severe COVID-19 is often associated with elevated autoantibody titers, the underlying mechanism has been unclear. Here, we investigated repertoires and reactivities of immunoglobulins derived from blood plasmablasts (PBs) in COVID-19 patients. This uncovered robust clonal expansion of PBs secreting cardiolipin (CL)-reactive autoantibodies in humoral response to SARS-CoV-2. About half of the expanded CL-reactive clones were also reactive to SARS-CoV-2 antigens and derived from SARS-CoV-2-specific primary responses as well as seasonal coronavirus-reactive memory responses. One such clone, CoV1804, was reactive to both CL and viral nucleocapsid (N), and exhibited anti-nucleolar activity in human cells. Repertoire analysis identified antibodies sharing genetic features with CoV1804 in COVID-19 patient-derived immunoglobulins from our and other cohorts, thereby constituting a novel public antibody. These public autoantibodies had numerous mutations that enhanced anti-N reactivity. On the other hand, anti-CL reactivity fluctuated through somatic hypermutation, which instead resulted in the acquisition of additional self-reactivities, including anti-nucleolar activity in the progeny. Thus, potentially CL-reactive precursors may have developed multiple reactivities to different self-antigens through clonal expansion driven by viral antigens. Our results unraveled a unique process of autoantibody production during COVID-19 and provide novel insights into the origin of virus-induced autoantibodies.

2024-09-11 | GSE233522 | GEO

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