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

doi:10.1038/nm1496

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

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252 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 language	English (US)
Pages (from-to)	378-383
Number of pages	6
Journal	Nature medicine
Volume	13
Issue number	3
DOIs	https://doi.org/10.1038/nm1496
State	Published - Mar 2007

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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title = "Humanization of autoantigen",

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.",

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

note = "Funding Information: 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.)",

year = "2007",

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doi = "10.1038/nm1496",

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AU - Nishie, Wataru

AU - Sawamura, Daisuke

AU - Goto, Maki

AU - Ito, Kei

AU - Shibaki, Akihiko

AU - McMillan, James R.

AU - Sakai, Kaori

AU - Nakamura, Hideki

AU - Olasz, Edit

AU - Yancey, Kim B.

AU - Akiyama, Masashi

AU - Shimizu, Hiroshi

N1 - Funding Information: 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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N2 - 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.

AB - 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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Humanization of autoantigen

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