Nishie Wataru, Sawamura Daisuke, Goto Maki, Ito Kei, Shibaki Akihiko, McMillan James R, Sakai Kaori, Nakamura Hideki, Olasz Edit, Yancey Kim B, Akiyama Masashi, Shimizu Hiroshi
Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
Nat Med. 2007 Mar;13(3):378-83. doi: 10.1038/nm1496. Epub 2007 Feb 25.
Transmissibility of characteristic lesions to experimental animals may help us understand the pathomechanism of human autoimmune disease. Here we show that human autoimmune disease can be reproduced using genetically engineered model mice. Bullous pemphigoid (BP) is the most common serious autoimmune blistering skin disease, with a considerable body of indirect evidence indicating that the underlying autoantigen is collagen XVII (COL17). Passive transfer of human BP autoantibodies into mice does not induce skin lesions, probably because of differences between humans and mice in the amino acid sequence of the COL17 pathogenic epitope. We injected human BP autoantibody into Col17-knockout mice rescued by the human ortholog. This resulted in BP-like skin lesions and a human disease phenotype. Humanization of autoantigens is a new approach to the study of human autoimmune diseases.
特征性病变向实验动物的传播可能有助于我们理解人类自身免疫性疾病的发病机制。在此我们表明，使用基因工程模型小鼠可以重现人类自身免疫性疾病。大疱性类天疱疮（BP）是最常见的严重自身免疫性水疱性皮肤病，大量间接证据表明潜在的自身抗原是ⅩⅦ型胶原蛋白（COL17）。将人类BP自身抗体被动转移到小鼠体内不会诱发皮肤病变，这可能是由于人类和小鼠COL17致病表位的氨基酸序列存在差异。我们将人类BP自身抗体注射到由人类直系同源基因拯救的Col17基因敲除小鼠体内。这导致了BP样皮肤病变和人类疾病表型。自身抗原人源化是研究人类自身免疫性疾病的一种新方法。
