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: 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
• Journal: Nature medicine (Nat Med) Vol. 13 Issue 3 Pg. 378-83 (Mar 2007) ISSN: 1078-8956 [Print] United States
• PMID: 17322897 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Autoantibodies
• Autoantigens
• Non-Fibrillar Collagens
• collagen type XVII

Topics

• Animals
• Autoantibodies (physiology)
• Autoantigens (chemistry, genetics, immunology)
• Female
• Humans
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Mice, Transgenic
• Non-Fibrillar Collagens (deficiency, genetics)
• Pemphigoid, Bullous (immunology)