title: An independent role of protective HLA class II alleles in rheumatoid arthritis severity and susceptibility.
abstract: OBJECTIVE
  To prospectively investigate the effect of the DERAA-encoding HLA alleles on disease susceptibility and severity in a large cohort of patients with rheumatoid arthritis (RA), and to differentiate protective effects from non-predisposition by comparing subgroups of patients with an equal amount of predisposition alleles.
  
  
  METHODS
  HLA class II alleles were determined in 440 patients with early RA and in 423 healthy controls. In order to study the effect of HLA on disease severity, radiographic joint destruction was evaluated, using the modified Sharp/van der Heijde method, during 4 years of followup.
  
  
  RESULTS
  The presence of DERAA-encoding HLA-DRB1 alleles conferred a lower risk of developing RA for both the presence and absence of SE alleles (odds ratio 0.6). At all time points, radiographic destruction was significantly less severe in DERAA-positive patients with 1 SE allele compared with DERAA-negative patients with 1 SE allele. Additionally, a protective effect of DERAA was detected in the groups of patients who were prone to having more severe disease because of the presence of anti-cyclic citrullinated peptide antibodies or because of smoking.
  
  
  CONCLUSIONS
  DERAA-encoding HLA-DRB1 alleles independently protect against RA and are associated with less severe disease.
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, RC Leiden, The Netherlands. AvdHelm@lumc.nl
authors.forename: Annette H M
authors.initials: AH
authors.lastname: van der Helm-van Mil
authors.forename: Tom W J
authors.initials: TW
authors.lastname: Huizinga
authors.forename: Geziena M Th
authors.initials: GM
authors.lastname: Schreuder
authors.forename: Ferdinand C
authors.initials: FC
authors.lastname: Breedveld
authors.forename: René R P
authors.initials: RR
authors.lastname: de Vries
authors.forename: René E M
authors.initials: RE
authors.lastname: Toes
mesh_terms: D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000473:pathology; D001175:Arthrography; D042241:Early Diagnosis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D007596:Joints / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D016017:Odds Ratio; D011446:Prospective Studies
chemical_list: D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains