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

Abstract:

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.

journal_name

Ann Rheum Dis

authors

Mewar D,Marinou I,Coote AL,Moore DJ,Akil M,Smillie D,Dickson MC,Binks MH,Montgomery DS,Wilson AG

doi

10.1136/ard.2007.075382

subject

Has Abstract

pub_date

2008-07-01 00:00:00

pages

980-3

issue

7

eissn

0003-4967

issn

1468-2060

pii

ard.2007.075382

journal_volume

67

pub_type

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