TY - JOUR
T1 - Hla–drb1 alleles in polymyalgia rheumatica, giant cell arteritis, and rheumatoid arthritis
AU - Weyand, Cornelia M.
AU - Hunder, Naomi N.H.
AU - Hicok, Kevin C.
AU - Hunder, Gene G.
AU - Goronzy, Jörg J.
PY - 1994/12
Y1 - 1994/12
N2 - 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.
AB - 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.
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U2 - 10.1002/art.1780370411
DO - 10.1002/art.1780370411
M3 - Article
C2 - 8147928
AN - SCOPUS:0028296110
SN - 0004-3591
VL - 37
SP - 514
EP - 520
JO - Arthritis & Rheumatism
JF - Arthritis & Rheumatism
IS - 4
ER -