HLA antigen associations with extra-articular rheumatoid arthritis

Seventy-seven patients with rheumatoid arthritis were investigated to examine the frequency of HLA antigens and their relationship to clinical and serological manifestations of extra-articular disease. The phenotype frequencies of DR4, DRw53, Bw62 and Cw3 were significantly increased, compared to normal controls, and there were negative associations with DR2 and DR7. The HLA antigen in strongest association with rheumatoid arthritis was DR4 (73.6%) and the relationship with DRw53 appeared to be secondary. The frequency of DR4 rose to 92% in seropositive patients with extra-articular disease manifestations whose serum contained immune complexes. A high frequency of DR4 was also seen in male patients (86%), reaching 100% in the small group of seropositive male patients with immune complexes. It is suggested that extra-articular disease represents a manifestation of severe classical rheumatoid arthritis and is not an 'overlap' syndrome. We propose that the HLA haplotype Cw3-Bw62-Dw4-DR4-DRw53 makes a greater genetic contribution to disease susceptibility in both extra-articular and male rheumatoid arthritis patients than in other subsets of RA.