Department of Dermatology, University of Freiburg, Freiburg, Germany.
Cell Mol Life Sci. 2010 Apr;67(8):1343-51. doi: 10.1007/s00018-009-0256-3. Epub 2010 Jan 20.
The pathomechanism of antibody-mediated tissue damage in autoimmune diseases can be best studied in experimental models by passively transferring specific autoantibodies into animals. The reproduction of the disease in animals depends on several factors, including the cross-reactivity of patient autoantibodies with the animal tissue. Here, we show that autoantibodies from patients with epidermolysis bullosa acquisita (EBA), a subepidermal autoimmune blistering disease, recognize multiple epitopes on murine collagen VII. Indirect immunofluorescence microscopy revealed that EBA patients' IgG cross-reacts with mouse skin. Overlapping, recombinant fragments of murine collagen VII were used to characterize the reactivity of EBA sera and to map the epitopes on the murine antigen by ELISA and immunoblotting. The patients' autoantibody binding to murine collagen VII triggered pathogenic events as demonstrated by a complement fixing and an ex vivo granulocyte-dependent dermal-epidermal separation assay. These findings should greatly facilitate the development of improved disease models and novel therapeutic strategies.
自身免疫性疾病中抗体介导的组织损伤的发病机制可以通过将特异性自身抗体被动转移到动物体内来在实验模型中进行最佳研究。动物疾病的重现取决于几个因素，包括患者自身抗体与动物组织的交叉反应性。在这里，我们显示来自获得性大疱性表皮松解症（EBA）患者的自身抗体识别表皮下自身免疫性水疱病的多个表皮 VII 胶原表位。间接免疫荧光显微镜显示 EBA 患者的 IgG 与小鼠皮肤发生交叉反应。使用重叠的重组小鼠 VII 型胶原片段通过 ELISA 和免疫印迹来表征 EBA 血清的反应性并绘制小鼠抗原上的表位。通过补体固定和体外嗜中性粒细胞依赖性真皮-表皮分离测定，证明患者的自身抗体与小鼠 VII 型胶原的结合引发了致病事件。这些发现将极大地促进改进疾病模型和新的治疗策略的发展。
