HLA and rheumatoid arthritis: susceptibility or severity?

An analysis of data collected on 440 British Caucasoid rheumatoid arthritis patients has confirmed positive association with HLA-DR4, Dw4, DRw53, and A2 and negative associations with HLA-DR2, 3, and 7. HLA-DR4 is more associated with RA 'severity' than with RA 'susceptibility', when measured by the parameters of ARA classification, seropositivity, severity of erosions and extra-articular manifestations. The association between HLA-A2, Cw3, Bw62, DR4, DRw53, and Dw4 and extra-articular disease has been confirmed in this study. The analysis of HLA and RA severity with respect to sex showed high frequencies of DR4, Dw4, and DRw53 in females, which increased in those with severe erosions, seropositivity or extra-articular disease. In males with RA, the disease appears to be associated not only with DR4, Dw4 and DRw53, but also with A2, Cw3 and Bw62. However, no significant differences in these antigen frequencies were found between male patients with severe RA and those without. Despite a significant decrease in the frequencies of DR3, B8 and A1 in most RA patient subsets, RA patients with Sjogren's syndrome showed a marked increase of A1 and B8 and patients with auto-antibodies had a significant increase in HLA-DR3 frequency when compared with patients without these features.