A common major histocompatibility complex class II allele HLA-DQB1*0301 is present in clinical variants of pemphigoid
A common major histocompatibility complex class II allele HLA-DQB1*0301 is present in clinical variants of pemphigoid
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DOI：
10.1073/pnas.93.16.8569
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发表时间：
1996-08-06
影响因子：
11.1
通讯作者：
Ahmed, R
中科院分区：
文献类型：
--
作者：
Delgado, JC;Turbay, D;Ahmed, R
大疱性类天疱疮 (BP) 是一种自身免疫性表皮下水疱性疾病，主要见于老年人。其临床特征是出现紧张的大疱和抗基底膜抗体的存在。在BP中，参与自身免疫的抗原是表皮基底膜肽BPAg1和BPAg2。我们将 21 名 BP 患者、17 名眼部瘢痕性类天疱疮 (OCP) 患者和 22 名口腔类天疱疮 (OP) 患者的主要组织相容性复合体 II 类基因座 (HLA-DRB1、DQB1) 的高分辨率分型与一组 218 个正常个体的单倍型进行了比较。我们发现三种疾病（BP、OCP 和 OP 与 DQB1*0301 显着相关（分别为 P = 0.005、P < 0.0001 和 P = 0.001）。等位基因 DQB1*0302、*0303 和 *06 的频率，它们共享第 71 至 77 位的特定氨基酸序列(Thr-Arg-Ala-Glu-Leu-Val-Thr) 也增加 (P = 0.01)，我们认为相同的主要组织相容性复合体 II 类等位基因 (DQB1*0301) 是易感性增强的常见标记，并且位置 71-77 具有相同的氨基酸残基 (DQB1*0301、-0302、-0305、-0602、 -0603 等位基因）存在于 BP、OCP 和 OP 患者中，我们的研究结果表明，类天疱疮的三种不同临床变体中的自身免疫反应涉及 T 细胞对 DQB1 的 II 类区域的识别，该区域与来自结膜、口腔粘膜和皮肤的基底膜的肽结合。
Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease seen primarily in elderly persons. It is characterized clinically by the development of tense bullae and by the presence of an antibasement membrane antibody. In BP, the antigens involved in the autoimmunity are epidermal basement membrane peptides BPAg1 and BPAg2. We have compared high resolution typing of major histocompatibility complex class II loci (HLA-DRB1, DQB1) in 21 patients with BP, 17 with ocular cicatricial pemphigoid (OCP), and 22 with oral pemphigoid (OP) to a panel of 218 haplotypes of normal individuals. We found that the three diseases (BP, OCP, and OP have significant association with DQB1*0301 (P = 0.005, P < 0.0001, and P = 0.001, respectively). The frequencies of alleles DQB1*0302, *0303, and *06, which share a specific amino acid sequence from position 71 to 77 (Thr-Arg-Ala-Glu-Leu-Val-Thr) were also increased (P = 0.01). We suggest that an identical major histocompatibility complex class II allele (DQB1*0301) is a common marker for enhanced susceptibility and that the same amino acid residues in positions 71-77 (DQB1*0301, -0302, -0305, -0602, -0603 alleles) are found in patients with BP, OCP, and OP. Our findings propose that the autoimmune response in the three different clinical variants of pemphigoid, involves the recognition by T cells of a class II region of DQB1, bound to a peptide from the basement membrane of conjunctiva, oral mucosa, and skin.