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Overlap of Characteristic Serological Antibodies in Rheumatoid Arthritis and Wheat-Related Disorders.

ABSTRACT: Background and Aims:Rheumatoid arthritis (RA) and celiac disease (CD) are members of the autoimmune disease family while they have been shown to share multiple aspects in epidemiology and clinical manifestations. The aim of this study was to assess the presence of wheat protein antibodies in RA seropositive subjects and the presence of RA diagnostic markers in subjects with seropositive wheat-related disorders including CD. Methods:Serum samples were collected from 844 subjects with joint pain and/or gastrointestinal symptoms and tested by a CD panel (anti-tTG and anti-DGP), a Wheat Zoomer (WZ) antibody panel (IgG/IgA to 14 wheat proteins), and a RA panel (anti-CCP and anti-RF). Retrospective analysis was completed using de-identified clinical data and test results. Results:The prevalence of RA markers was first investigated in CD- or WZ-positive subjects and negative controls. 49 subjects were seropositive in the CD panel with 10 (20%) RA positivity. 605 subjects were seropositive in the WZ panel with 106 (18%) RA positivity. 222 subjects were seronegative in either panels with 12 (6%) RA positivity. Next, the frequency of the CD markers and the clinically relevant wheat protein antibodies were investigated in the RA-positive subjects and negative controls. 128 subjects in this cohort were seropositive in the RA panel with 10 (8%) CD positivity and 106 (83%) WZ positivity, compared to 716 RA seronegative controls with 39 (5%) CD positivity and 499 (70%) WZ positivity. Conclusions:Our data presents an apparent trend of overlapped serological antibody biomarker positivity in RA and wheat-related disorders.

SUBMITTER: Yang Y

PROVIDER: S-EPMC6348907 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Overlap of Characteristic Serological Antibodies in Rheumatoid Arthritis and Wheat-Related Disorders.

Yang Yuanyuan Y Deshpande Payal P Krishna Karthik K Ranganathan Vinodh V Jayaraman Vasanth V Wang Tianhao T Bei Kang K Rajasekaran John J JJ Krishnamurthy Hari H

Disease markers 20190110

<h4>Background and aims</h4>Rheumatoid arthritis (RA) and celiac disease (CD) are members of the autoimmune disease family while they have been shown to share multiple aspects in epidemiology and clinical manifestations. The aim of this study was to assess the presence of wheat protein antibodies in RA seropositive subjects and the presence of RA diagnostic markers in subjects with seropositive wheat-related disorders including CD.<h4>Methods</h4>Serum samples were collected from 844 subjects wi ...[more]

PMID: 30755781

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Project description:ObjectiveAnti-citrullinated protein antibodies (ACPAs) and rheumatoid factor (RF) are commonly present in rheumatoid arthritis (RA) without a clear rationale for their coexistence. Moreover, autoantibodies develop against proteins with different posttranslational modifications and native proteins without obvious unifying characteristics of the antigens. We undertook this study to broadly evaluate autoantibody binding in seronegative and seropositive RA to identify novel features of reactivity.MethodsAn array was created using a total of 172,828 native peptides, citrulline-containing peptides, and homocitrulline-containing peptides derived primarily from proteins citrullinated in the rheumatoid joint. IgG and IgM binding to peptides were compared between cyclic citrullinated peptide (CCP)-positive RF+, CCP+RF-, CCP-RF+, and CCP-RF- serum from RA patients (n = 48) and controls (n = 12). IgG-bound and endogenously citrullinated peptides were analyzed for amino acid patterns and predictors of intrinsic disorder, i.e., unstable 3-dimensional structure. Binding to IgG-derived peptides was specifically evaluated. Enzyme-linked immunosorbent assay confirmed key results.ResultsBroadly, CCP+RF+ patients had high citrulline-specific IgG binding to array peptides and CCP+RF- and CCP-RF+ patients had modest citrulline-specific IgG binding (median Z scores 3.02, 1.42, and 0.75, respectively; P < 0.0001). All RA groups had low homocitrulline-specific binding. CCP+RF+ patients had moderate IgG binding to native peptides (median Z score 2.38; P < 0.0001). The highest IgG binding was to citrulline-containing peptides, irrespective of protein identity, especially if citrulline was adjacent to glycine or serine, motifs also seen in endogenous citrullination in the rheumatoid joint. Highly bound peptides had multiple features predictive of disorder. IgG from CCP+RF+ patients targeted citrulline-containing IgG-derived peptides.ConclusionDisordered antigens, which are frequently citrullinated, and common epitopes for ACPAs and RF are potentially unifying features for RA autoantibodies.

Dataset Information

Overlap of Characteristic Serological Antibodies in Rheumatoid Arthritis and Wheat-Related Disorders.

Publications

Overlap of Characteristic Serological Antibodies in Rheumatoid Arthritis and Wheat-Related Disorders.

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