Weyand C M, Hunder N N, Hicok K C, Hunder G G, Goronzy J J
Mayo Clinic and Foundation, Rochester, Minnesota 55905.
Arthritis Rheum. 1994 Apr;37(4):514-20. doi: 10.1002/art.1780370411.
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.
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.
The HLA-DRB104 allele was the most frequent among PMR patients (67%). While the expression of allelic variants of the HLA-DR4 family was restricted to HLA-DRB10401 and 0404/8 in RA patients, all HLA-DRB104 alleles, including B10402 and B10403, were represented in the PMR group. The distribution of HLA-DRB1 alleles among HLA-DRB104 negative patients was similar in those with PMR and those with GCA, and could be distinguished from that in RA patients. In particular, HLA-DRB101 alleles, which were found in most HLA-DRB1*04 negative RA patients, were underrepresented in patients with PMR and GCA.
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.
免疫遗传学分析表明，巨细胞动脉炎（GCA）和类风湿关节炎（RA）与人类白细胞抗原DR4（HLA - DR4）分子的两个不同结构域相关。本研究旨在评估风湿性多肌痛（PMR）在免疫遗传学上是类似于GCA还是RA，并确定HLA - DRB1等位基因的表达是否可用于检测PMR患者之间的异质性。
通过等位基因特异性扩增及随后的寡核苷酸杂交，对46例PMR患者、52例GCA患者、122例血清学阳性RA患者和72名正常个体进行HLA - DRB1等位基因分型。
HLA - DRB104等位基因在PMR患者中最为常见（67%）。在RA患者中，HLA - DR4家族等位基因变体的表达仅限于HLA - DRB10401和0404/8，而在PMR组中，所有HLA - DRB104等位基因，包括B10402和B10403，均有出现。在HLA - DRB104阴性患者中，PMR患者和GCA患者的HLA - DRB1等位基因分布相似，且与RA患者的分布不同。特别是，在大多数HLA - DRB104阴性RA患者中发现的HLA - DRB1*01等位基因，在PMR和GCA患者中所占比例较低。
PMR中HLA - DRB1等位基因的分布类似于GCA中的分布。PMR和GCA共享由HLA - DRB1基因第二高变区（HVR）编码的相关序列多态性。PMR和GCA的HLA - DRB1关联可与RA的相区分，RA与DRB1等位基因第三HVR中的一个序列基序相关。HLA - DR分子不同结构域的不同作用表明，这些分子调节多种生物学功能，且它们对疾病机制的贡献不同。PMR和GCA中HLA - DRB1等位基因分布的相似性表明，HLA - DRB1等位基因不能预测PMR向GCA特征性血管病变的进展。
