RHEUMATOID-FACTOR, HLA-DR4, AND ALLELIC VARIANTS OF DRB1 IN WOMEN WITH RECENT-ONSET RHEUMATOID-ARTHRITIS

Objective. To examine the relationship of rheumatoid factor (RF) to HL A-DR4 and alleles of DRB1 in women with recent-onset rheumatoid arthri tis (RA). Methods. Incident cases of RA were identified as part of a p rospective, population-based case-control study. HLA typing was comple ted for 246 cases meeting criteria for definite or classic RA. Results . One hundred thirty-six patients (55%) were positive for DR4, and 130 (53%) were RF positive. DR4 was found to be strongly associated with seropositivity (odds ratio 4.1, P < 0.0001). Patients with a shorter i nterval from RA onset to RF testing had a higher frequency of seroposi tivity than those with a longer interval (less than or equal to 18 mon ths 60%, >18 months 33%). Further analysis of patients who had RF test ing within 18 months of RA onset showed that the frequency of seroposi tivity was significantly greater among DR4-positive patients who had t he shared sequence stretch of DR beta 1 associated with RA susceptibil ity (76% RF positive) than among DR1-positive patients who had this se quence (45% RF positive) (odds ratio 3.8, P = 0.01). Moreover, the fre quency of seropositivity among DR1-positive patients with the sequence did not differ from that among all patients without the shared sequen ce (47%) (odds ratio 0.9, P = 0.8). Conclusion. HLA-DR4 is strongly as sociated with seropositivity in women with recent-onset RA. The amino acid sequence of DR beta 1 that is associated with susceptibility to R A and is shared between DR4 and DR1 appears not to be the primary dete rminant of seropositivity in these women.