Association of HLA-DR antigens with disease severity in Japanese patients with rheumatoid arthritis

Abstract

Twenty eight Japanese patients with rheumatoid arthritis (RA) were tested for HLA-DR antigens to investigate genetic influence on disease severity and prognosis. The severity of RA was assessed by clinical, laboratory and radiological indexes. HLA-A, B, C and DR typing was performed using sera described at the 3rd Asia and Oceania Histocompatibility Workshop. HLA-DR4.1 was significantly higher in RA patients (50%) compared with controls (27.6%). HLA-DRw53 was also higher in RA patients, although DRw52 was lower in those than controls. When the relationship between HLA-DR antigens and the clinical severity of RA was investigated, the patients with HLA-DR4 had a severer disease than DR4 negative patients. In contrast, HLA-DR2 positive patients had significantly better functional scores than DR 2 negative patients. We next investigated specific genes likely to be directly involved in the pathogenesis of RA. Although the new restriction fragment length polymorphisms (RFLPs) were found in DR2 positive patients, no association was found between the RFLPs and the clinical severity of RA. Furthermore there were no differences in the frequencies of the RFLPs in HLA-DR4 positive patients compared with DR4 negative patients. It may be concluded that the severity of RA appears to be influenced by several different genes or molecules rather than by a single gene or gene product linked to HLA-DR2 or DR4.