Research article

A new classification of HLA-DRB1 alleles differentiates predisposing and protective alleles for autoantibody production in rheumatoid arthritis

Pierre-Antoine Gourraud¹, Philippe Dieudé², Jean-Frédéric Boyer^3,4, Leonor Nogueira⁵, Anne Cambon-Thomsen⁷, Bernard Mazières^3,4, François Cornélis⁶, Guy Serre⁵, Alain Cantagrel^3,4 and Arnaud Constantin^1,3,4

¹  Service d'Epidémiologie CHU Toulouse, INSERM, U558, Université Paul Sabatier Toulouse III, Faculté de Médecine, 37 allées Jules Guesde, Toulouse Cedex 7, 31073, France

²  Service de Rhumatologie, CHU Bichat Claude-Bernard, 46 rue Henri Huchard, Paris, 75018, France

³  GRCB40, UFR Sciences Médicales Rangueil, 1 avenue du Professeur Jean Poulhès, Toulouse Cedex 9, 31059, France

⁴  Service de Rhumatologie, CHU Toulouse Rangueil, 1 avenue du Professeur Jean Poulhès, Toulouse Cedex 9, 31059, France

⁵  Laboratoire de Biologie Cellulaire et Cytologie, CHU Toulouse Purpan, Place du Docteur Baylac, Toulouse cedex 9, 31059, France

⁶  GenHotel, Genopole, 2 rue Gaston Crémieux, Evry Cedex, 91057, France

⁷  INSERM, U558, Faculté de Médecine, 37 allées Jules Guesde, Toulouse Cedex 7, 31073, France

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Arthritis Research & Therapy 2007, 9:R27doi:10.1186/ar2131

Published:	12 March 2007

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.