THE EFFECT OF HLA-DR GENES ON SUSCEPTIBILITY TO AND SEVERITY OF ANKYLOSING-SPONDYLITIS

Objective. To analyze the effect of HLA-DR genes on susceptibility to and severity of ankylosing spondylitis (AS). Methods. Three hundred si xty-three white British AS patients were studied; 149 were carefully a ssessed for a range of clinical manifestations, and disease severity w as assessed using a structured questionnaire. Limited HLA class I typi ng and complete HLA-DR typing were performed using DNA-based methods, HLA data from 13,634 healthy white British bone marrow donors were use d for comparison. Results. A significant association between DR1 and A S was found, independent of HLA-B27 (overall odds ratio [OR] 1.4, 95% confidence interval [95% CI] 1.1-1.8, P = 0.02; relative risk [RR] 2.7 , 95% CI 1.5-4.8, P = 6 x 10(-4) among homozygotes; RR 2.1, 95% CI 1.5 -2.8, P = 5 x 10(-6) among heterozygotes). A large but weakly signific ant association between DR8 and AS was noted, particularly among DR8 h omozygotes (RR 6.8, 95% CI 1.6-29.2, P = 0.01 among homozygotes; RR 1. 6, 95% CI 1.0-2.7, P = 0.07 among heterozygotes), A negative associati on with DR12 (OR 0.22, 95% CI 0.09-0.5, P = 0.001) was noted. HLA-DR7 was associated with younger age at onset of disease (mean age at onset 18 years for DR7-positive patients and 23 years for DR7-negative pati ents; Z score 3.21, P = 0.001). No other HLA class I or class II assoc iations with disease severity or with different clinical manifestation s of AS were found. Conclusion. The results of this study suggest that HLA-DR genes may have a weak effect on susceptibility to AS independe nt of HLA-B27, but do not support suggestions that they affect disease severity or different clinical manifestations.