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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Competing interests: MCD, MHB and DSM are employed by the study sponsor.
Funding: This work was funded by a research grant from GlaxoSmithKline R&D, UK (Genetics of Rheumatoid Arthritis; GORA).
Ethics approval: Research ethics committee approval was obtained for the study and all subjects gave informed consent.
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