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.
authors.affiliation: Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Nishie
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sawamura
authors.forename: Maki
authors.initials: M
authors.lastname: Goto
authors.forename: Kei
authors.initials: K
authors.lastname: Ito
authors.forename: Akihiko
authors.initials: A
authors.lastname: Shibaki
authors.forename: James R
authors.initials: JR
authors.lastname: McMillan
authors.forename: Kaori
authors.initials: K
authors.lastname: Sakai
authors.forename: Hideki
authors.initials: H
authors.lastname: Nakamura
authors.forename: Edit
authors.initials: E
authors.lastname: Olasz
authors.forename: Kim B
authors.initials: KB
authors.lastname: Yancey
authors.forename: Masashi
authors.initials: M
authors.lastname: Akiyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shimizu
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000502:physiology; D001324:Autoantigens / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D005260:Female; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D024041:Non-Fibrillar Collagens / Q000172:deficiency / Q000235:genetics*; D010391:Pemphigoid, Bullous / Q000276:immunology*; D000097805:Collagen Type XVII
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D024041:Non-Fibrillar Collagens; D000097805:Collagen Type XVII