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

Abstract

Objective. To examine the relationship of rheumatoid factor (RF) to HLA-DR4 and alleles of DRBl in women with recent-onset rheumatoid arthritis (RA).Methods. Incident cases of RA were identified as part of a prospective, population-based cas-ontrol 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 (518 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 DRPl 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-

HLA markers and prediction of clinical course and outcome in rheumatoid arthritis

“…While some investigators have claimed a significant diseasemodifying influence of DR4, in that DR4-positive patients were shown to develop a higher degree of destructive joint disease than DR4-negative patients (10,(19)(20)(21), other investigators could not confirm such a relationship (22,23). Similarly, the association between HLA markers and seropositivity or the presence of nodular disease remains controversial (24)(25)(26). In addition to the association of particular clinical presentations with HLA, a gene-dose effect was appreciated for DR4 and the presence of the shared epitope, since patients homozygous for these markers more often exhibited systemic manifestations such as Felty's syndrome and extraarticular organ involvement (27).…”

Early rheumatoid arthritis: can we predict its outcome?

“…In one study, the highest disease penetrance occurred with genotypes *0401 and *0404/*0102 for males, but with *0401/*0401 for females 81 . In Caucasians, RF is positively linked with DRB1*04 SE‐containing alleles 61,63 and negatively linked with DRB1*01 SE‐containing alleles 67,82 . An association with nodules, which are uncommon in seronegative patients, is less clear.…”

When does rheumatoid arthritis begin and why do we need to know?

“…Many studies have evaluated whether certain HLA types are more frequent in seropositive versus seronegative patients. Several have shown that HLA-DR4 is strongly associated with seropositive RA (56)(57)(58)(59)(60)(61)(62). Ploski et al (58) noted that certain subtypes, particularly DRB1*0401 and DRB1*0408, were associated with what was described as "clearly seropositive disease."…”