Abstract
The HLA-DRB1 gene was reported to be associated with anticitrullinated protein/peptide autoantibody (ACPA) production in rheumatoid arthritis (RA) patients. A new classification of HLA-DRB1 alleles, reshaping the shared epitope (SE) hypothesis, was recently found relevant in terms of RA susceptibility and structural severity.We investigated the relevance of this new classification of HLA-DRB1 SE+ alleles in terms of rheumatoid factor (RF) and ACPA production in a sample of French RA patients.We studied 160 early RA patients included in a prospective longitudinal cohort of French Caucasian patients with recent-onset arthritis. RF, anticyclic citrullinated peptide 2 (anti-CCP2) and antideiminated human fibrinogen autoantibodies (AhFibA) were assessed in all patients at inclusion. The HLA-DRB1 gene was typed by PCR-sequence specific oligonucleotides probes (PCR-SSOP), and SE+ alleles were classified into four groups (S1, S2, S3P, S3D) according to the new classification.The new classification of HLA-DRB1 SE+ alleles distinguishes predisposing and protective alleles for RF, anti-CCP2 or AhFibA production. The presence of S2 or S3P alleles is associated with both RF, anti-CCP2 or AhFibA positivity, whereas the presence of S3D or S1 alleles appears to be protective for RF, anti-CCP2 or AhFibA positivity.The new classification of HLA-DRB1 SE+ alleles is relevant in terms of autoantibody production in early RA patients by differentiating predisposing and protective alleles for RF or ACPA production.
Highlights
Since early rheumatoid arthritis (RA) is often indistinguishable from other inflammatory joint diseases, recent-onset inflammatory synovitis poses a diagnostic and prognostic challenge to rheumatologists [1]
We investigated the relevance of this new classification of HLA-DRB1 alleles in terms of rheumatoid factor (RF) and anticitrullinated protein/peptide autoantibody (ACPA) production in a cohort of French Caucasian patients with early RA
Demographic and immunologic characteristics of RA patients The main baseline demographic and immunologic characteristics of the 160 patients with early RA included in the present study were the following: 120 women (75%) and 40 men (25%); mean (± standard deviation) age, 50.31 (± 14.03) years; mean (± standard deviation) disease duration, 0.55 (± 0.02) years; number (%) RF-positive, 110/160 (68.75%); number (%) anti-CCP2 antibody-positive, 110/160 (68.75%); and number (%) antideiminated human fibrinogen autoantibodies (AhFibA)-positive, 108/160 (67.25%)
Summary
Since early rheumatoid arthritis (RA) is often indistinguishable from other inflammatory joint diseases, recent-onset inflammatory synovitis poses a diagnostic and prognostic challenge to rheumatologists [1]. ACPA = anticitrullinated protein/peptide autoantibody; AhFibA = antideiminated human fibrinogen autoantibodies; anti-CCP = anticyclic citrullinated peptide; ELISA = enzyme-linked immunosorbent assay; HLA = human leukocyte antigen; MHC = minor histocompatibility complex, PCR = polymerase chain reaction; RA = rheumatoid arthritis; RF = rheumatoid factor; SE = shared epitope. Arthritis Research & Therapy Vol 9 No 2 Gourraud et al. Among immunologic markers, anticitrullinated protein/peptide antibodies (ACPAs) constitute relevant tools in the diagnosis and prognosis of early RA. The citrulline moiety is the true determinant in proteins recognized by antiperinuclear factor [5], antikeratin antibodies [6], antifilaggrin antibodies [7], anticyclic citrullinated peptide (anti-CCP) antibodies [8] and antideiminated human fibrinogen autoantibodies (AhFibA) [9,10,11]. ACPAs represent a prognostic factor for erosive disease in early RA [20,21,22,23,24]
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