Sesarman Alina, Sitaru Cassian
Department of Dermatology, University of Freiburg, Freiburg, Germany.
Methods Mol Biol. 2013;961:371-87. doi: 10.1007/978-1-62703-227-8_25.
Epidermolysis bullosa acquisita (EBA) is an autoimmune subepidermal blistering disease caused by an autoreactive response against collagen VII, the major constituent of the anchoring fibrils at the epidermal basement membrane. The pathogenic relevance of collagen VII-specific autoantibodies has been conclusively demonstrated ex vivo and in experimental animals using antibody passive transfer models. To study the mechanisms of autoantibody production and tissue damage an animal model reproducing both the autoimmune response and the active skin disease is needed. In the present protocol, we describe the induction of an autoimmune response and active disease by immunizing mice with recombinant murine collagen VII and the analysis of the induced disease phenotype. The humoral and cellular immune response elicited in mice by immunization with the autoantigen, as well as the induced skin pathology replicate the features of the human disease at the clinical, histo- and immunopathological levels. Thus, this model is an excellent tool for investigating the mechanisms underlying pathogenic autoantibody production, the autoantibody-mediated tissue injury, and for the development of more effective therapeutic strategies in autoimmune diseases.
获得性大疱性表皮松解症（EBA）是一种自身免疫性表皮下大疱性疾病，由针对Ⅶ型胶原蛋白的自身反应性应答引起，Ⅶ型胶原蛋白是表皮基底膜锚定原纤维的主要成分。使用抗体被动转移模型在体外和实验动物中已确凿证明了Ⅶ型胶原蛋白特异性自身抗体的致病相关性。为了研究自身抗体产生和组织损伤的机制，需要一种能够重现自身免疫反应和活动性皮肤病的动物模型。在本方案中，我们描述了通过用重组鼠Ⅶ型胶原蛋白免疫小鼠来诱导自身免疫反应和活动性疾病，以及对诱导的疾病表型进行分析。用自身抗原免疫小鼠所引发的体液和细胞免疫反应，以及诱导的皮肤病理学变化，在临床、组织学和免疫病理学水平上重现了人类疾病的特征。因此，该模型是研究致病性自身抗体产生机制、自身抗体介导的组织损伤以及开发自身免疫性疾病更有效治疗策略的极佳工具。
