Humanization of autoantigen
Humanization of autoantigen
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DOI：
10.1038/nm1496
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发表时间：
2007-03-01
期刊：
影响因子：
82.9
通讯作者：
Shimizu, Hiroshi
中科院分区：
文献类型：
--
作者：
Nishie, Wataru;Sawamura, Daisuke;Shimizu, Hiroshi
特征性病变对实验动物的可传递性可能有助于我们理解人类自身免疫性疾病的病理机制。在这里，我们表明，人类自身免疫性疾病可以复制使用基因工程模型小鼠。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胶原XVII（COL17）。将人BP自身抗体被动转移到小鼠中不会诱导皮肤病变，这可能是因为人和小鼠之间在COL17致病性表位的氨基酸序列上存在差异。我们将人BP自身抗体注射到由人直系同源物拯救的Col17敲除小鼠中。这导致BP样皮肤病变和人类疾病表型。自身抗原的人源化是研究自身免疫性疾病的新途径。
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.