Miyagawa S, Higashimine I, Iida T, Yamashina Y, Fukumoto T, Shirai T
Department of Dermatology, Nara Medical University, Japan.
J Invest Dermatol. 1997 Nov;109(5):615-8. doi: 10.1111/1523-1747.ep12337585.
It has previously been demonstrated that susceptibility to pemphigus vulgaris is associated with human leukocyte antigen (HLA)-DR4 serologic specificity among Ashkenase Jews, and with DR4 as well as DR6 (DR14) in other ethnic groups. We genotyped HLA-DRB1, DQA1, DQB1, and DPB1 alleles in 16 patients with pemphigus by polymerase chain reaction-restriction fragment length polymorphism, to find evidence of potential HLA class II allele associations with pemphigus in Japanese patients who have a relatively homogeneous ethnic background. All nine patients with pemphigus vulgaris and five of seven patients with pemphigus foliaceus carried one or two alleles of HLA-DRB104 (0403, 0406) and HLA-DRB114 (1401, 1405, 1406) subtypes. Sequence analysis of these DRB104 and DRB114 alleles revealed the amino acid homology of phenylalanine at position 26 and valine at position 86 with the DRB10402 allele that reportedly confers a strong susceptibility to pemphigus vulgaris in Ashkenazi Jews. Thus our findings, together with previous HLA studies on pemphigus vulgaris patients of different ethnic groups, suggest that HLA-DRB104 and DRB114 alleles are commonly associated with pemphigus vulgaris across racial barriers. These HLA-DRB1 alleles are likely to be also associated with pemphigus foliaceus. Further studies on more diverse ethnic populations will be helpful in determining the significance of the association between certain amino acid residues of the class II molecules and disease susceptibility to pemphigus vulgaris as well as pemphigus foliaceus.
此前已有研究表明，寻常型天疱疮易感性在德系犹太人中与人类白细胞抗原（HLA）-DR4血清学特异性相关，而在其他种族群体中与DR4以及DR6（DR14）相关。我们采用聚合酶链反应-限制性片段长度多态性方法，对16例天疱疮患者的HLA-DRB1、DQA1、DQB1和DPB1等位基因进行基因分型，以寻找在种族背景相对单一的日本患者中，潜在的HLAⅡ类等位基因与天疱疮相关性的证据。所有9例寻常型天疱疮患者以及7例落叶型天疱疮患者中的5例，携带一个或两个HLA-DRB104（0403、0406）和HLA-DRB114（1401、1405、1406）亚型的等位基因。对这些DRB104和DRB114等位基因的序列分析显示，其第26位的苯丙氨酸和第86位的缬氨酸与DRB10402等位基因具有氨基酸同源性，据报道该等位基因赋予德系犹太人对寻常型天疱疮较强的易感性。因此，我们的研究结果与之前对不同种族寻常型天疱疮患者的HLA研究一起表明，HLA-DRB104和DRB114等位基因在不同种族间普遍与寻常型天疱疮相关。这些HLA-DRB1等位基因可能也与落叶型天疱疮相关。对更多不同种族人群进行进一步研究，将有助于确定Ⅱ类分子某些氨基酸残基与寻常型天疱疮以及落叶型天疱疮疾病易感性之间关联的意义。
