Humanization of autoantigen.
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.
Nishie
Wataru
W
Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
Sawamura
Daisuke
D
Goto
Maki
M
Ito
Kei
K
Shibaki
Akihiko
A
McMillan
James R
JR
Sakai
Kaori
K
Nakamura
Hideki
H
Olasz
Edit
E
Yancey
Kim B
KB
Akiyama
Masashi
M
Shimizu
Hiroshi
H
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
D001323:Autoantibodies; D001324:Autoantigens; D024041:Non-Fibrillar Collagens; D000097805:Collagen Type XVII