Generation of a disease model for epidermolysis bullosa acquisita using autoantigen-humanized mice and application for the development of novel treatment

2010 Fiscal Year Final Research Report

• Project/Area Number: 20591312
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Dermatology
• Research Institution: Hokkaido University
• Principal Investigator: SHIBAKI Akihiko Hokkaido University, 大学院・医学研究科, 非常勤講師 (40291231)
• Co-Investigator(Kenkyū-buntansha): AKIYAMA Masashi 名古屋大学, 大学院・医学系研究科, 教授 (60222551)
• Co-Investigator(Renkei-kenkyūsha): ITO Kei 北海道大学, 大学院・医学研究科, 非常勤講師 (20421977)
• Project Period (FY): 2008 – 2010
• Keywords: 皮膚病理学 / 免疫 / 治療 / 臨床 / 自己免疫性疾患 / 動物モデル / リンパ球

Research Abstract

We tried to develop an active disease model for epidermolysis bullosa acquisita which produce IgG against human type VII collagen (COL7). Immunized wild type mice with recombinant human COL7 protein with adjuvant produced high titer of anti-human COL7 IgG antibody in vivo. We injected those IgG in neonatal COL7-humanized mice intraperitonealy. We observed the linear deposition of IgG at the basement membrane zone. To develop an active model for EBA, we generated immunodeficient COL7-humanized mice. Splenocytes isolated from immunized wild type mice were transferred into immunodeficient COL7-humanized mice. However, the recipient mice produced no anti-human COL7 IgG or developed no skin changes.

Research Products

• [Journal Article] Blockade of autoantibody-initiated tissue damage by using recombinant Fab antibody fragments against pathogenic autoantigen. (2010)
  • Author(s): Wang G, Ujiie H, Shibaki A, Nishie W, Tateishi Y, Kikuchi K, Li Q, McMillan JR, Morioka H, Sawamura D, Nakamura H, Shimizu H.
  • Journal Title: American Journal of Pathology 176 Pages: 914-25
  • Peer Reviewed
• [Journal Article] A novel active mouse model for bullous pmephigoid targeting humanized pathogenic antigen. (2010)
  • Author(s): Ujiie H, Shibaki A, Nishie W, Sawamura D, Wang G, Tateishi Y, Li Q, Moriuchi R, Qiao H, Nakamura H, Akiyama M, Shimizu H.
  • Journal Title: Journal of Immunology 184 Pages: 2166-74
  • Peer Reviewed
• [Journal Article] Human IgG1 monoclonal antibody against human collagen 17 noncollagenous 16A domain induces blisters via complement activation in experimental bullous pemphigoid model. (2010)
  • Author(s): Li Q, Ujiie H, Shibaki A, Wang G, Moriuchi R, Qiao HJ, Morioka H, Shinkuma S, natsuga K, Long HA, Nishie W, Shimizu H.
  • Journal Title: Journal of Immunology 185 Pages: 7746-55
  • Peer Reviewed
• [Journal Article] What's new in bullous pemphigoid. (2010)
  • Author(s): Ujiie H, Shibaki A, Nishie W, Shimizu H.
  • Journal Title: Journal of Dermatology 37 Pages: 194-204
• [Journal Article] Collagen XVII participates in keratinocyte adhesion to collagen IV, and in p38-MAPK-dependetn migration and cell signaling. (2009)
  • Author(s): Qiao H, Shibaki A, Long HA, Wang G, Li Q, Nishie W, Abe R, Akiyama M, Shimizu H, McMillan JR.
  • Journal Title: Journal of Investigative Dermatology 129 Pages: 2288-95
  • Peer Reviewed
• [Journal Article] Disseminated cutaneous Mycobacterium kansasii infection in a patient infected with the human immunoceficiency virus. (2009)
  • Author(s): Nomura Y, Nishie W, Shibaki A, Ibata M, Shimizu H.
  • Journal Title: Clinical and Experimental Dermatology 34 Pages: 625-6
  • Peer Reviewed
• [Journal Article] Keratinocyte-/fibroblast-targeted rescue of Col7a1-disrupted mice and generation of an exact dystrophic epidermolysis bullosa model using human COL7A1 mutation. (2009)
  • Author(s): Ito K, Sawamura D, Goto M, Nakamura H, Nishie W, Sakai K, Natsuga K, Shinkuma S, Shibaki A, Uitto J, Denton CP, Nakajima O, Akiyama M, Shimizu H.
  • Journal Title: American Journal of Pathology 175 Pages: 2508-17
  • Peer Reviewed
• [Journal Article] Cutaneous pemphigus vulgaris with skin features similar to the classic mucocutaneous type : a case report and review of the literature. (2008)
  • Author(s): Shinkuma S, Nishie W, Shibaki A, Sawamura D, Ito K, Tsuji-Abe Y, Natsuga K, Chan PT, Amagai m, Shimizu H.
  • Journal Title: Clinical and Experimental Dermatology 33 Pages: 724-8
  • Peer Reviewed
• [Presentation] Human IgG1 mAb against human COL17 NC16A developed from BP patients induces blisters in experimental bullous pemphigoid model. (2010)
  • Author(s): Shibaki A.
  • Organizer: Society for Investigative Dermatology Annual Meeting
  • Place of Presentation: Hilton Atlanta, Atlanta, Georgia. (USA)
  • Year and Date: 2010-05-08
• [Presentation] Pathomechanism in bullous pemphigoid- evidence from the model animal-. (2009)
  • Author(s): Shibaki A.
  • Organizer: The 4^<th> Joint Meeting of Japanese Dermatological Association and Australasian College of Dermatologists
  • Place of Presentation: 札幌市
  • Year and Date: 2009-07-10
• [Presentation] Development of an active disease model for bullous pemphigoid. (2008)
  • Author(s): Ujiie H, Shibaki A, et al.
  • Organizer: International Investigative Dermatology 2008
  • Place of Presentation: 京都市
  • Year and Date: 2008-05-17