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Association between radiographic severity of rheumatoid arthritis and shared epitope alleles: differing mechanisms of susceptibility and protection
  1. Devesh Mewar (dmewar{at}doctors.org.uk)
  1. University of Sheffield, United Kingdom
    1. Ioanna Marinou (mdp04im{at}sheffield.ac.uk)
    1. University of Sheffield, United Kingdom
      1. Annabel L Coote (annabelcoote{at}hotmail.com)
      1. University of Sheffield, United Kingdom
        1. David J Moore (david.moore{at}sth.nhs.uk)
        1. University of Sheffield, United Kingdom
          1. Mohammed Akil (m.akil{at}shef.ac.uk)
          1. University of Sheffield, United Kingdom
            1. David Smillie (david.smillie{at}nbs.nhs.uk)
            1. National Blood Transfusion Service, United Kingdom
              1. Marion C Dickson (marion.c.dickson{at}gsk.com)
              1. GlaxoSmithKline, United Kingdom
                1. Michael H Binks (michael.h.binks{at}gsk.com)
                1. GlaxoSmithKline, United Kingdom
                  1. Douglas S Montgomery (doug.s.montgomery{at}gsk.com)
                  1. GlaxoSmithKline, United Kingdom
                    1. Anthony G Wilson (a.g.wilson{at}shef.ac.uk)
                    1. University of Sheffield, United Kingdom

                      Abstract

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

                      Methods: Patients with RA (n=962) were studied. Genotyping of DRB1 alleles and assays of rheumatoid factor (RF) and anti-cyclic citrullinated peptides (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 both anti-CCP and RF (P<0.0001). 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 rheumatoid factor, 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.

                      • DRB1
                      • anti-CCP
                      • modified Larsen score
                      • rheumatoid arthritis
                      • rheumatoid factor

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