Association between radiographic severity of rheumatoid arthritis and shared epitope alleles: differing mechanisms of susceptibility and protection

Devesh Mewar ¹, Ioanna Marinou ¹, Annabel L Coote ¹, David J Moore ¹, Mohammed Akil ¹, David Smillie ², Marion C Dickson ³, Michael H Binks ³, Douglas S Montgomery ³ and Anthony G Wilson ^1*

¹ University of Sheffield, United Kingdom
² National Blood Transfusion Service, United Kingdom
³ GlaxoSmithKline, United Kingdom

^* To whom correspondence should be addressed. E-mail: a.g.wilson{at}shef.ac.uk.

Accepted 23 September 2007

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.

Keywords: DRB1, anti-CCP, modified Larsen score, rheumatoid arthritis, rheumatoid factor

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