MOLECULAR ANALYSIS OF HLA-DR POLYMORPHISM IN POLYMYALGIA-RHEUMATICA

Objective. To analyze by molecular typing possible associations of HLA -DRB1 alleles with polymyalgia rheumatica (PMR) compared to controls a nd patients with rheumatoid arthritis (RA) in Switzerland. Methods. In a multicenter survey, we recruited 100 patients with PMR with and wit hout signs of giant cell arteritis (GCA), 198 with RA, and 200 control s (volunteer bone marrow donors). HLA-DR generic typing was performed by microtiter plate oligotyping and DR4 subtypes analyzed by dot blot hybridization with sequence specific oligonucleotides or by polymerase chain reaction sequence specific primers. Results. DR4 and DR1 tended to be increased in PMR, compared to controls (36 vs 30%, p=0.30; and 19 vs 12%, p=0.16, respectively). Frequencies of all RA associated DR4 and DR1 subtypes tended to be increased in PMR as well. Frequency of the HLA-DR beta 1 70-74 shared motif (QK/RRAA) was significantly highe r in PMR than in controls [50 vs 16%, odds ratio (OR)=1.8, p=0.018], a lthough lower than in RA (77 vs 36%, OR=6.0, P <0.0001), and slightly out of the range of significance if a Bonferroni correction was applie d (p=0.1). At double dose, this epitope was also increased in PMR, but not significantly (5 vs 2%, OR=2.6, p=0.17), while it was markedly au gmented in RA (22 vs 2%, OR=14, p=<0.0001). In patients with the share d epitope, the frequency of clinical signs of GCA tended to be increas ed (19 vs 10%, p=0.25). Frequency of the HLA-DR beta 1 DRYF 28-31 moti f was identical in PMR (95%) and controls (93%). Conclusion. PMR may b e associated with the HLA-DR beta 1 70-74 shared epitope. This associa tion, however, would be much weaker for PMR than for RA, particularly with the shared:epitope at double dose. PMR is clearly not associated with the HLA-DR beta 1 DRYF 28-31 motif.