RESEARCH - Association between radiographic severity of RA and shared epitope alleles: differing mechanisms of susceptibility and protection

June 13, 2008

Published Online First: 27 September 2007. doi:10.1136/ard.2007.075382

ls of the Rheumatic Diseases 2008;67:980-983

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EXTENDED REPORTS

Association between radiographic severity of rheumatoid arthritis and

shared epitope alleles: differing mechanisms of susceptibility and

protection

D Mewar 1, I Marinou 1, A L Coote 1, D J 1, M Akil 1, D Smillie

2, M C Dickson 3, M H Binks 3, D S Montgomery 3, A G 1

1 School of Medicine and Biomedical Sciences, University of Sheffield,

Sheffield, UK

2 National Blood Transfusion Service, Sheffield, UK

3 GlaxoKline R & D, age, Hertfordshire, UK

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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Not an MD

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