OBJECTIVE: Immunogenetic analysis has demonstrated that giant cell arteritis (GCA) and rheumatoid arthritis (RA) are associated with 2 different domains of the HLA-DR4 molecule. The present study was undertaken to evaluate whether polymyalgia rheumatica (PMR) immunogenetically resembles GCA or RA and to determine whether expression of HLA-DRB1 alleles can be used to detect heterogeneity among PMR patients. METHODS: Forty-six patients with PMR, 52 with GCA, 122 with seropositive RA, and 72 normal individuals were genotyped for HLA-DRB1 alleles by allele-specific amplification and subsequent oligonucleotide hybridization. RESULTS: The HLA-DRB1*04 allele was the most frequent among PMR patients (67%). While the expression of allelic variants of the HLA-DR4 family was restricted to HLA-DRB1*0401 and *0404/8 in RA patients, all HLA-DRB1*04 alleles, including B1*0402 and B1*0403, were represented in the PMR group. The distribution of HLA-DRB1 alleles among HLA-DRB1*04 negative patients was similar in those with PMR and those with GCA, and could be distinguished from that in RA patients. In particular, HLA-DRB1*01 alleles, which were found in most HLA-DRB1*04 negative RA patients, were underrepresented in patients with PMR and GCA. CONCLUSION: The distribution of HLA-DRB1 alleles in PMR resembles that found in GCA. PMR and GCA share the associated sequence polymorphism encoded by the second hypervariable region (HVR) of the HLA-DRB1 gene. The HLA-DRB1 association of PMR and GCA can be distinguished from that of RA, which is linked to a sequence motif in the third HVR of DRB1 alleles. The differential role of distinct domains on HLA-DR molecules suggests that multiple biologic functions are regulated by these molecules and that they contribute differently to disease mechanisms. The similarities in the distribution of HLA-DRB1 alleles in PMR and GCA indicates that HLA-DRB1 alleles are not predictive for progression of PMR to the vasculitic lesions that are pathognomonic for GCA.
OBJECTIVE: Immunogenetic analysis has demonstrated that giant cell arteritis (GCA) and rheumatoid arthritis (RA) are associated with 2 different domains of the HLA-DR4 molecule. The present study was undertaken to evaluate whether polymyalgia rheumatica (PMR) immunogenetically resembles GCA or RA and to determine whether expression of HLA-DRB1 alleles can be used to detect heterogeneity among PMR patients. METHODS: Forty-six patients with PMR, 52 with GCA, 122 with seropositive RA, and 72 normal individuals were genotyped for HLA-DRB1 alleles by allele-specific amplification and subsequent oligonucleotide hybridization. RESULTS: The HLA-DRB1*04 allele was the most frequent among PMR patients (67%). While the expression of allelic variants of the HLA-DR4 family was restricted to HLA-DRB1*0401 and *0404/8 in RApatients, all HLA-DRB1*04 alleles, including B1*0402 and B1*0403, were represented in the PMR group. The distribution of HLA-DRB1 alleles among HLA-DRB1*04 negative patients was similar in those with PMR and those with GCA, and could be distinguished from that in RApatients. In particular, HLA-DRB1*01 alleles, which were found in most HLA-DRB1*04 negative RApatients, were underrepresented in patients with PMR and GCA. CONCLUSION: The distribution of HLA-DRB1 alleles in PMR resembles that found in GCA. PMR and GCA share the associated sequence polymorphism encoded by the second hypervariable region (HVR) of the HLA-DRB1 gene. The HLA-DRB1 association of PMR and GCA can be distinguished from that of RA, which is linked to a sequence motif in the third HVR of DRB1 alleles. The differential role of distinct domains on HLA-DR molecules suggests that multiple biologic functions are regulated by these molecules and that they contribute differently to disease mechanisms. The similarities in the distribution of HLA-DRB1 alleles in PMR and GCA indicates that HLA-DRB1 alleles are not predictive for progression of PMR to the vasculitic lesions that are pathognomonic for GCA.
Authors: C Salvarani; L Boiardi; V Mantovani; A Ranzi; F Cantini; I Olivieri; M Bragliani; E Collina; P Macchioni Journal: Ann Rheum Dis Date: 1999-05 Impact factor: 19.103
Authors: Rogelio J Palomino-Morales; Tomas R Vazquez-Rodriguez; Orlando Torres; Inmaculada C Morado; Santos Castañeda; Jose A Miranda-Filloy; Jose L Callejas-Rubio; Benjamin Fernandez-Gutierrez; Miguel A Gonzalez-Gay; Javier Martin Journal: Arthritis Res Ther Date: 2010-03-23 Impact factor: 5.156