Analysis of pathomechanism of blister formation in pemphigus vulgaris using post-embedding immuno-electron microscopy

• Project/Area Number: 23591629
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Toho University
• Principal Investigator: ISHIKO Akira 東邦大学, 医学部, 教授 (10202988)
• Research Collaborator: ISHII Ken 東邦大学, 医学部, 准教授 (50296670) ; YOSHIDA Kenji 東邦大学, 医学部, 大学院生
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 天疱瘡 / デスモグレイン / デスモソーム / 免疫電顕 / デスモグレイン3 / 棘融解 / 自己免疫性水疱症 / 電子顕微鏡 / 水疱症 / 自己免疫

Research Abstract

In order to give an insight into the pathophysiological mechanism of blister formation in pemphigus vulgaris, we performed ultrastructural experiments using novel monoclonal antibodies against dsg3 injected into organ-cultured human skin. A monoclonal antibody having ability to induce blister reached extracellular surface of desmosomes in all layers of epidermis within 2 hours, but did not induce acantholysis yet. After 22 hours, acantholysis developed and desmosomal structures and dsg3 molecules were disappeared from the keratinocytes cell surface. Some amount of dsg3 were detected in the cytoplasm. Using non-pathogenic monoclonal antibody instead of the pathogenic antibody, nothing of above mentioned changes were observed. These results suggest both steric hinderans and dsg3 internalization occurs in our system within 22 hours, although more precise time-course observation is expected to show dynamic mechanism of blister formation.

Research Products

• [Presentation] Combination of pemphigus foliaceus IgG monoclonal antibodies (mAbs) promotes desmoglein 1 clustering (2014)
  • Author(s): Kenji Yoshida, Ken Ishii, Atsushi Shimizu, Mariko Yokouchi, John Stanley, Akira Ishiko
  • Organizer: 73rd annual meeting of Society for Investigative Dermatology
  • Place of Presentation: Alvuquerque, New Mexico, USA (Oral presentation)
  • Year and Date: 2014-05-09
• [Presentation] Combination of pemphigus foliaceus IgG monoclonal antibodies (mAbs) promotes desmoglein 1 clustering
  • Author(s): Kenji Yoshida, Ken Ishii, Atsushi Shimizu, Mariko Yokouchi, John Stanley, Akira Ishiko
  • Organizer: 73rd Society for Investigative Dermatology
  • Place of Presentation: Albuquerque, New Mexico, USA
• [Presentation] 水疱症の最新の話題
  • Author(s): 石河 晃
  • Organizer: 第3回とちぎ皮膚免疫疾患研究会
  • Place of Presentation: 宇都宮グランドホテル（栃木県）
  • Invited
• [Presentation] 自己免疫性水疱症の最新の話題
  • Author(s): 石河 晃
  • Organizer: 皮膚疾患フォーラム
  • Place of Presentation: 三鷹産業プラザ（東京都）
  • Invited
• [Book] エキスパートに学ぶ皮膚病理診断学 棘融解を呈する代表的疾患の病理組織学的鑑別点 (2012)
  • Author(s): 石河 晃
  • Publisher: 中山書店