Rheumatoid factor, HLA–DR4, and allelic variants of DRB1 in women with recent‐onset rheumatoid arthritis

AbstractObjective. To examine the relationship of rheumatoid factor (RF) to HLA–DR4 and alleles of DRB1 in women with recent‐onset rheumatoid arthritis (RA).Methods. Incident cases of RA were identified as part of a prospective, population‐based case–control study. HLA typing was completed 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 interval from RA onset to RF testing had a higher frequency of seropositivity than those with a longer interval (≤18 months 60%, >18 months 33%). Further analysis of patients who had RF testing within 18 months of RA onset showed that the frequency of seropositivity was significantly greater among DR4‐positive patients who had the shared sequence stretch of DRβ1 associated with RA susceptibility (76% RF positive) than among DR1‐positive patients who had this sequence (45% RF positive) (odds ratio 3.8, P = 0.01). Moreover, the frequency of seropositivity among DR1‐positive patients with the sequence did not differ from that among all patients without the shared sequence (47%) (odds ratio 0.9, P = 0.8).Conclusion. HLA–DR4 is strongly associated with seropositivity in women with recent‐onset RA. The amino acid sequence of DRβ1 that is associated with susceptibility to RA and is shared between DR4 and DR1 appears not to be the primary determinant of seropositivity in these women.