HLA-DRB1 alleles associated with polymyalgia rheumatica in northern Italy:correlation with disease severity

Objective-To examine the association of HLA-DRB1 alleles with polymyalgia r heumatica (PMR) in a Mediterranean country and to explore the role of HLA-D RB1 genes in determining disease severity. Methods-A five year prospective follow up study of 92 consecutive PMR patie nts diagnosed by the secondary referral centre of rheumatology of Reggio Em ilia, Italy was conducted. HLA-DRB1 alleles were determined in the 92 patie nts, in 29 DR4 positive rheumatoid arthritis (RA) patients, and in 148 cont rols from the same geographical area by polymerase chain reaction amplifica tion and oligonucleotide hybridisation. Results-No significant differences were observed in the frequencies of HLA- DRB1 types and in the expression of HLA-DRB 70-74 shared motif between PMR and controls. The frequency of the patients with double dose of epitope was low and not significantly different in PMR and in controls. No significant differences in the distribution of HLA-DR4 subtypes were observed between DR4+ PMR, DR+ RA, and DR4+ controls. Results of the univariate analysis ind icated that an erythrocyte sedimentation rate (ESR) at diagnosis > 72 mm 1s t h, the presence of HLA-DR1, DR10, rheumatoid epitope, and the type of rhe umatoid epitope were significant risk factors associated with relapse/ recu rrence. Cox proportional hazards modelling identified two variables that in dependently increased the risk of relapse/recurrence: ESR at diagnosis > 72 mm 1st h (RR=1.5) and type 2 (encoded by a non-DR4 allele) rheumatoid epit ope (RR=2.7). Conclusion-These data from a Mediterranean country showed no association of rheumatoid epitope with PMR in northern Italian patients. A high ESR at di agnosis and the presence of rheumatoid epitope encoded by a non-DR4 allele are independent valuable markers of disease severity.