Humanization of autoantigen (original) (raw)

Nature Medicine volume 13, pages 378–383 (2007)Cite this article

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.

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Acknowledgements

We thank M. Sato, A. Honda, A. Nagasaki and E. Nishizono for technical assistance. This work was supported in part by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (15390336, 17209038 and 18013002 to H.S.; 17659331, 18390309 and 18659315 to D.S.); by the Project for Realization of Regenerative Medicine from the Ministry of Education, Science, Sports and Culture of Japan (2003–2007 to H.S.); by a grant from the US National Institutes of Health (RO1 AR048982 to K.B.Y.); by a grant from Nu Skin Japan; and by Health and Labour Sciences Research Grants from the Ministry of Health, Labour and Welfare of Japan (2004–2006 to H.S.)

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Author notes

  1. Wataru Nishie and Daisuke Sawamura: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, 060-8638, Japan
    Wataru Nishie, Daisuke Sawamura, Maki Goto, Kei Ito, Akihiko Shibaki, James R McMillan, Kaori Sakai, Hideki Nakamura, Masashi Akiyama & Hiroshi Shimizu
  2. Department of Dermatology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, 53226, Wisconsin, USA
    Edit Olasz & Kim B Yancey

Authors

  1. Wataru Nishie
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  2. Daisuke Sawamura
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  3. Maki Goto
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  4. Kei Ito
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  5. Akihiko Shibaki
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  6. James R McMillan
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  7. Kaori Sakai
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  8. Hideki Nakamura
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  9. Edit Olasz
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  10. Kim B Yancey
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  11. Masashi Akiyama
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  12. Hiroshi Shimizu
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Corresponding author

Correspondence toHiroshi Shimizu.

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Nishie, W., Sawamura, D., Goto, M. et al. Humanization of autoantigen.Nat Med 13, 378–383 (2007). https://doi.org/10.1038/nm1496

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