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A New Classification of HLA-DRB1 Alleles Differentiates Predisposing and Protective Alleles for Autoantibody Production in Rheumatoid Arthritis

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. © 2007 Gourraud et al., licensee BioMed Central Ltd.
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https://hal.archives-ouvertes.fr/hal-02084374
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Submitted on : Friday, March 29, 2019 - 3:37:00 PM
Last modification on : Monday, June 29, 2020 - 2:20:04 PM

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Pierre-Antoine Gourraud, Philippe Dieudé, Jean-Frédéric Boyer, Leonor Nogueira, Anne Cambon-Thomsen, et al.. A New Classification of HLA-DRB1 Alleles Differentiates Predisposing and Protective Alleles for Autoantibody Production in Rheumatoid Arthritis. Arthritis Research and Therapy, BioMed Central, 2007, 9, pp.Pages 1208-1212. ⟨10.1186/ar2131⟩. ⟨hal-02084374⟩

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