POLYMYALGIA RHEUMATICA IS ASSOCIATED WITH BOTH HLA-DRB1^*0401 and DRBl^*0404

Abstract

The frequency of HLA-DRB1 alleles was determined in 68 Caucasoid patients with polymyalgia rheumatica (PMR) and 140 controls using polymerase chain reaction (PCR) sequence-specific oligonucleotide typing. In keeping with previous studies, an increased frequency of DRB1*04 was observed in patients [55.9% vs 35.0%, odds ratio (OR) 2.4, 95% confidence interval (CI) 1.3-4.4]. HLA-DRB1*0101 frequency was also increased in patients, although less confidence could be placed on this association (19.1% vs 14.3%, OR 1.4, 95% CI 0.6-3.3). HLA-DRB1*04 subtyping indicated that the frequencies of both DRB1*0401 (38.2% vs 22.1%, OR 2.2, 95% CI 1.0-4.3) and DRB1*0404 (16.2% vs 5.0%, OR 3.7, 95% CI 1.2-11.1) were specifically raised. An increased frequency of the RA shared epitope (QKRAA/QRRAA) was also observed in this group (75.0% vs 44.2%, OR 3.8, 95% CI 1.9-7.6). When the analysis was restricted to only DRB1*04-negative patients and controls, the frequencies of DRB1*0301, *11 and *08 were marginally raised. However, no obvious relationship appeared to exist between PMR susceptibility and DRB1 alleles carrying the DYF conserved epitope in the second hypervariable region. Autoantibodies to thyroid antigens were present in 23% of patients. An increased frequency of DRB1*0301 was observed in patients with thyroid microsomal antibodies compared to those without (54.5% vs 24.6%, OR 3.7, 95% CI 0.8-17.0). This increase was not observed in patients with thyroglobulin autoantibodies. These data indicate that both DRB1*0401 and *0404 are associated with PMR, and that this may extend to include DRB1*0101. The immunogenetic profile of susceptibility markers in this condition appears to be similar to that in rheumatoid arthritis.