title: A new classification of HLA-DRB1 alleles differentiates predisposing and protective alleles for rheumatoid arthritis structural severity.
abstract: OBJECTIVE
  A new classification of HLA-DRB1 alleles supporting the shared epitope hypothesis of rheumatoid arthritis (RA) susceptibility was recently introduced. We investigated the relevance of this classification in terms of the structural severity of RA.
  
  
  METHODS
  The study group comprised 144 patients who were included in a prospective longitudinal cohort of French Caucasoid patients with early RA. Progression of the total radiographic damage score (Sharp/van der Heijde method) was used to quantify the structural severity of RA after 4 years of followup. HLA-DRB1 typing and subtyping were performed by polymerase chain reaction, using a panel of sequence-specific oligonucleotide probes. HLA-DRB1 alleles were classified according to the above-mentioned new system. The association between the HLA-DRB1 allele groups (S1, S2, S3P, S3D, and X) and the structural severity of RA was analyzed with nonparametric statistical tests.
  
  
  RESULTS
  The presence of S2 alleles (HLA-DRB1*0401 and HLA-DRB1*1303) was associated with severe forms of RA (P = 0.004); a significant dose effect was observed (P = 0.01). The presence of S3D alleles (HLA-DRB1*11001, HLA-DRB1*1104, HLA-DRB1*12, and HLA-DRB1*16) was associated with benign forms of RA (P < 0.0001), and a significant dose effect was observed (P < 0.01).
  
  
  CONCLUSIONS
  The studied classification of HLA-DRB1 alleles is relevant in terms of RA outcomes. Compared with a previously described classification system, this system differentiates predisposing (S2) and protective (S3D) alleles for RA structural severity, which, respectively, correspond to KRRAA and DRRAA amino acid patterns at position 70-74 of the third hypervariable region of the HLA-DRbeta chain.
authors.affiliation: INSERM U558, Toulouse, France.
authors.forename: Pierre-Antoine
authors.initials: PA
authors.lastname: Gourraud
authors.forename: Jean-Frédéric
authors.initials: JF
authors.lastname: Boyer
authors.forename: Thomas
authors.initials: T
authors.lastname: Barnetche
authors.forename: Michel
authors.initials: M
authors.lastname: Abbal
authors.forename: Anne
authors.initials: A
authors.lastname: Cambon-Thomsen
authors.forename: Alain
authors.initials: A
authors.lastname: Cantagrel
authors.forename: Arnaud
authors.initials: A
authors.lastname: Constantin
mesh_terms: D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology; D018450:Disease Progression; D018604:Epitope Mapping; D000939:Epitopes / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006684:HLA-DR Antigens / Q000145:classification* / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006239:Haplotypes; D006801:Humans; D008297:Male; D011379:Prognosis; D011446:Prospective Studies; D011859:Radiography; D012720:Severity of Illness Index
chemical_list: D000939:Epitopes; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553505:HLA-DRB1*04:01 antigen