Association of HLA-DR4 with a more progressive disease course in patients with rheumatoid arthritis. Results of a followup study.

The association between HLA-DR antigens and rheumatoid arthritis (RA) was investigated in a well-characterized cohort of RA patients who were followed from the beginning of the disease (mean followup 6 years). The frequencies of HLA-DR antigens in patients with possible or probable RA (n = 49) were similar to those in controls. In patients with definite RA (n = 134), the frequencies of DR1, DR4, and DRw53 were increased, whereas the frequencies of DR2, DR3, DRw6, DRw13, and DRw52 were decreased, compared with controls. Comparison of HLA-DR frequencies in patients with definite RA subclassified according to the severity of the disease at the end of the followup period revealed a difference only in the frequency of DR4, which was increased in patients with progressive RA (59.2%) compared with those who had mild RA (34.8%). Further analysis showed that, compared with DR4-negative RA patients, DR4-positive patients had more swollen joints, higher scores on the Ritchie articular index, the Health Assessment Questionnaire, and the Steinbrocker functional classification, more radiologic abnormalities, and more use of second-line drugs. Also, the rate of progression of radiologic abnormalities, functional classification, and use of second-line drugs was higher in DR4-positive patients. We conclude that DR4 is associated with a more severe disease course, and is a prognostic marker in early RA.