An independent role of protective HLA class II alleles in rheumatoid arthritis severity and susceptibility

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Abstract
Objective To prospectively investigate the effect of the DERAA-encoding HLA alleles on disease susceptibility and severity in a large cohort of patients with rheumatoid arthritis (RA), and to differentiate protective effects from nonpredisposition by comparing subgroups of patients with an equal amount of predisposition alleles. Methods HLA class II alleles were determined in 440 patients with early RA and in 423 healthy controls. In order to study the effect of HLA on disease severity, radiographic joint destruction was evaluated, using the modified Sharp/van der Heijde method, during 4 years of followup. Results The presence of DERAA-encoding HLA–DRB1 alleles conferred a lower risk of developing RA for both the presence and absence of SE alleles (odds ratio 0.6). At all time points, radiographic destruction was significantly less severe in DERAA-positive patients with 1 SE allele compared with DERAA-negative patients with 1 SE allele. Additionally, a protective effect of DERAA was detected in the groups of patients who were prone to having more severe disease because of the presence of anti–cyclic citrullinated peptide antibodies or because of smoking. Conclusion DERAA-encoding HLA–DRB1 alleles independently protect against RA and are associated with less severe disease.