title: 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.
authors.affiliation: Service d'Epidémiologie CHU Toulouse, INSERM, U558, Université Paul Sabatier Toulouse III, Faculté de Médecine, 37 allées Jules Guesde, Toulouse Cedex 7, 31073, France.
authors.forename: Pierre-Antoine
authors.initials: PA
authors.lastname: Gourraud
authors.forename: Philippe
authors.initials: P
authors.lastname: Dieudé
authors.forename: Jean-Frédéric
authors.initials: JF
authors.lastname: Boyer
authors.forename: Leonor
authors.initials: L
authors.lastname: Nogueira
authors.forename: Anne
authors.initials: A
authors.lastname: Cambon-Thomsen
authors.forename: Bernard
authors.initials: B
authors.lastname: Mazières
authors.forename: François
authors.initials: F
authors.lastname: Cornélis
authors.forename: Guy
authors.initials: G
authors.lastname: Serre
authors.forename: Alain
authors.initials: A
authors.lastname: Cantagrel
authors.forename: Arnaud
authors.initials: A
authors.lastname: Constantin
mesh_terms: D000483:Alleles; D000917:Antibody Formation / Q000235:genetics*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006684:HLA-DR Antigens / Q000145:classification* / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012217:Rheumatoid Factor / Q000097:blood
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D012217:Rheumatoid Factor