Association of HLA alleles and clinical features in patients with synovitis of recent onset

Objective. To determine how HLA alleles are associated with the clinical di sease patterns of patients with synovitis of recent onset. Methods. The HLA alleles A, B, C, DR beta 1, and DQ beta 1 were determined in a cohort of 211 patients (mean age 42 years, 64% female, 79% white) with recent-onset synovitis in 1 or more peripheral joints, At a mean disease d uration of 33 weeks, 98 patients (46%) met the American College of Rheumato logy (ACR) criteria for rheumatoid arthritis (RA), 38 (18%) met the Europea n Spondylarthropathy Study Group criteria for spondylarthropathy (SpA), and 75 (36%) were classified as having undifferentiated arthropathy (UA). Cont rols were racially matched healthy individuals (n = 244). Results. Shared epitope (SE) alleles were significantly more common in rheu matoid factor-positive (RFS) patients fulfilling the ACR RA criteria than i n other patients with early arthritis (65% versus 35%; P < 0.001). In addit ion, the RA patients had by far the highest frequency of radiographic erosi ons (52% and 39% in RF+ and RF- RA, respectively, versus 3% and 9% in SpA a nd UA patients, respectively; P < 0.0001). The presence of SE alleles was a particularly strong predictor of early erosions in the RF- RA patients (od ds ratio [OR] 6.8, 95% confidence interval [95% CI] 1.2-45), The presence o f 2 SE alleles or an associated DQ beta 1*0301 (DQ7) or DQ beta 1*0302 (DQ8 ) allele appeared to modestly increase the risk of early erosions, although these DQ alleles were in strong linkage disequilibrium with DR beta 1*0401 , both in the patient and in the control populations. B27 was linked with t he presence of SE alleles in the patients, including those patients fulfill ing the RA criteria, but not in the controls (12%, versus 3%; P < 0.001). E nthesitis was present in 23 (11%) of 211 patients, was highly associated wi th B27 (OR 4.2, 95% CI 1.5-11.5), and surprisingly, was not a feature speci fic only to the SpA group. The B8-DR3 haplotype was significantly increased in the patient subgroups compared with controls (17% versus 7%; P < 0.01), although the clinical significance of this association is unclear. Conclusion. This study of HLA associations in a diverse cohort of early syn ovitis patients emphasizes the complex degree of genetic interaction betwee n alleles at several major histocompatibility complex loci, which regulates clinical phenotypes. In particular, SE and B27, while predisposing patient s to characteristic clinical syndromes, had an unexpected degree of associa tion in this cohort, perhaps explaining the overlap in clinical features in many patients.