Association between radiographic severity of rheumatoid arthritis and shared epitope alleles: differing mechanisms of susceptibility and protection.
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.
Mewar
D
D
School of Medicine and Biomedical Sciences, University of Sheffield, Beech Hill Road, Sheffield, UK.
Marinou
I
I
Coote
A L
AL
Moore
D J
DJ
Akil
M
M
Smillie
D
D
Dickson
M C
MC
Binks
M H
MH
Montgomery
D S
DS
Wilson
A G
AG
D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging* / Q000235:genetics* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood; D000939:Epitopes / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D008297:Male; D010456:Peptides, Cyclic / Q000276:immunology; D011859:Radiography; D012217:Rheumatoid Factor / Q000097:blood; D012720:Severity of Illness Index
D001323:Autoantibodies; D000939:Epitopes; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D012217:Rheumatoid Factor