Humanization of autoantigen

Wataru Nishie, Daisuke Sawamura, Maki Goto, Kei Ito, Akihiko Shibaki, James R. McMillan, Kaori Sakai, Hideki Nakamura, Edit Olasz, Kim B. Yancey, Masashi Akiyama, Hiroshi Shimizu

Research output: Contribution to journalArticle

216 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)378-383
Number of pages6
JournalNature medicine
Volume13
Issue number3
DOIs
StatePublished - Mar 1 2007

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Nishie, W., Sawamura, D., Goto, M., Ito, K., Shibaki, A., McMillan, J. R., Sakai, K., Nakamura, H., Olasz, E., Yancey, K. B., Akiyama, M., & Shimizu, H. (2007). Humanization of autoantigen. Nature medicine, 13(3), 378-383. https://doi.org/10.1038/nm1496