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Association between radiographic severity of rheumatoid arthritis and shared epitope alleles: differing mechanisms of susceptibility and protection
  1. D Mewar1,
  2. I Marinou1,
  3. A L Coote1,
  4. D J Moore1,
  5. M Akil1,
  6. D Smillie2,
  7. M C Dickson3,
  8. M H Binks3,
  9. D S Montgomery3,
  10. A G Wilson1
  1. 1
    School of Medicine and Biomedical Sciences, University of Sheffield, Sheffield, UK
  2. 2
    National Blood Transfusion Service, Sheffield, UK
  3. 3
    GlaxoSmithKline R&D, Stevenage, Hertfordshire, UK
  1. A G Wilson, School of Medicine and Biomedical Sciences, Beech Hill Road, Sheffield S10 2RX; a.g.wilson{at}


Objective: To investigate the association of a recently described classification of Human leukocyte antigen (HLA)-DRB1 shared epitope alleles with rheumatoid factors (RF) and anti-cyclic citrullinated peptide (CCP) production and radiological severity in rheumatoid arthritis (RA).

Methods: Patients with RA (n = 962) were studied. Genotyping of DRB1 alleles and assays for RF and anti-CCP were performed. Radiological severity was measured using the modified Larsen score.

Results: In accordance with previous reports, we found carriage of S2 alleles (K-R-A-A at positions 71–74) to be associated with more severe disease with a gene–dose effect (p = 0.0059), and also associated with the presence of anti-CCP and RF (p<0.001). Carriage of S1 alleles (D-E-R-A-A at positions 70–74) was associated with less severe disease (p = 0.01), however there was no association between S1 and either anti-CCP or RF, suggesting that the basis for this possible protective effect was not related to autoantibody-producing B cells.

Conclusions: These data suggest that multiple biological mechanisms underlie the DRB1 association with rheumatoid arthritis severity.

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  • Competing interests: MCD, MHB and DSM are employed by the study sponsor.

  • Funding: This work was funded by a research grant from GlaxoSmithKline R&D, UK (Genetics of Rheumatoid Arthritis; GORA).

  • Ethics approval: Research ethics committee approval was obtained for the study and all subjects gave informed consent.

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