麦醇溶蛋白与特异性HLA基因介导eTG/IgA复合体沉积致组织损伤在疱疹样皮炎中的作用机制

疱疹样皮炎（DH）是谷胶（主要为麦醇溶蛋白）诱发的慢性复发性自身免疫性疱病, 多伴有胃肠道症状。课题组既往报告DH病例占我国总报告数70%以上，建立了有效的临床病理诊断方法。基于此申请人前期发现HLA-B*08:01和-DRB1*03:01为中国DH的风险基因，而非欧洲诊疗指南中推荐检测的HLA-DQ2/8，论文发表于J Invest Dermatol。但该种群特异性HLA基因呈递麦醇溶蛋白与eTG/IgA复合体沉积于真皮乳头致DH组织损伤的机制尚不清楚。本项目拟在前期研究基础上对如下内容进行研究：1）麦醇溶蛋白多肽与特异性HLA基因在疱疹样皮炎疾病中的免疫呈递和损伤机制；2）谷胶饲养HLA-B8+/+/H-2-β2m-/-双转基因小鼠模型的构建及eTG/IgA复合体致组织损伤作用机制。以上两方面的研究将为深入理解疱疹样皮炎的发病机制，探寻精准诊疗方案提供理论依据。

Dermatitis herpetiformis (DH) is a chronic recurrent autoimmune blister disease induced by gluten (the main component is gliadin), often accompanied by gastrointestinal symptoms. Our team have reported more than 70% cases reported in Chinese population, and have established an effective clinicopathological diagnosis method. In addition, HLA-B*08:01 and -DRB1*03:01 were identified to be risk genes of DH in China, rather than the HLA-DQ2/8 recommended by the European management guidelines. Those results were published in J Invest Dermatol. However, the mechanism by how the population-specific HLA gene presenting the gliadin and deposited eTG/IgA complex in dermal papillae is still unclear. On the basis of previous studies, this project intends to study the following questions: 1) The peptide presentation and tissue damage mechanism of gliadin polypeptide and specific HLA genes in dermatitis herpetiformis; 2) construction of HLA-B8+/+/H-2-m-/- double transgenic mouse model fed with gluten and the mechanism of tissue damage induced by eTG/IgA complex. The above two aspects of research will provide theoretical basis for in-depth understanding of the pathogenesis of dermatitis herpetiformis and the exploration of precision diagnosis and treatment schemes.