Analysis of BP230 autoantibodies using a novel mouse model of bullous pemphigoid

• Project/Area Number: 21K08316
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Hirosaki University
• Principal Investigator: SAWAMURA Daisuke 弘前大学, 医学研究科, 客員研究員 (60196334)
• Co-Investigator(Kenkyū-buntansha): 松崎 康司 弘前大学, 医学研究科, 准教授 (50322946) ; 中野 創 弘前大学, 医学研究科, 准教授 (90281922)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Project Status: Completed (Fiscal Year 2023)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2023: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 類天疱瘡 / 自己抗体 / 自己免疫性疾患 / 基底膜 / 水疱 / 高齢者 / 皮膚 / 水疱症 / 自己免疫 / 抗体 / モデルマウス

Outline of Research at the Start

水疱性類天疱瘡は，高齢者に高発する最も頻度の高い自己免疫性水疱症であり，全身に表皮下水疱が多発する重篤な疾患である．本症患者の血清中には，皮膚の基底膜を認識する抗基底膜抗体が存在する．その自己抗体が認識する基底膜蛋白は，BP180とBP230である．本研究の核心をなす学術的な問いは，抗BP230自己抗体の病原性の詳細な解明，である．

Outline of Final Research Achievements

In bullous pemphigoid, mechanism where cytoplasmic protein BP230 become autoantigen is unknown. We succeeded in generation of a new BP230 model mouse. The purposes of this study were detailed analysis of autoantibodies and elucidation of pathogenesis of bullous pemphigoid. In this study, we examined pathogenicity and epitope of BP230 antibodies, investigated skin lesions after immunization of different peptides, and evaluated several therapies using the model mouse.

Academic Significance and Societal Importance of the Research Achievements

比較的頻度の高い抗BP180自己抗体を有する水疱性類天疱瘡は, その発症機構について詳細に検討され明らかにされてきた. それに比較して, 抗BP230自己抗体を有する水疱性類天疱瘡は, 頻度は低く, その臨床的特徴から最近注目され, その発症機構の解明が急がれている. 今回我々が行った本研究により，抗BP230自己抗体の本質が明らかとなり，抗BP230型の本症の臨床的な特徴, またどのような治療が適するのか，など皮膚科の臨床に直結する卓越した結果が期待できる．

Research Products

• [Journal Article] Native Autoantigen Complex Detects Pemphigoid Autoantibodies (2023)
  • Author(s): Mai Shoko、Izumi Kentaro、Mai Yosuke、Natsuga Ken、Ishii Norito、Sawamura Daisuke、Schauer Franziska、Kiritsi Dimitra、Nishie Wataru、Ujiie Hideyuki
  • Journal Title: JID Innovations Volume: 3 Issue: 3 Pages: 100193-100193
  • DOI: 10.1016/j.xjidi.2023.100193
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A 1,035-Subject Study Suggesting a History of Bone Fracture as a Possible Factor Associated with the Development of Anti-BP180 Autoantibodies. (2022)
  • Author(s): Mai Y, Izumi K, Sawada K, Akasaka E, Mai S, Sawamura D, Ihara K, Nakaji S, Nishie W.
  • Journal Title: J Invest Dermatol. Volume: 142 Issue: 3 Pages: 984-987.e3
  • DOI: 10.1016/j.jid.2021.11.028
  • Peer Reviewed / Open Access
• [Journal Article] The pathogeneses of pemphigus and pemphigoid diseases (2021)
  • Author(s): Ujiie H, Yamagami J, Takahashi H, Izumi K, Iwata H, Wang G, Sawamura D, Amagai M, Zillikens D.
  • Journal Title: J Dermatol Sci. Volume: 104 Issue: 3 Pages: 154-163
  • DOI: 10.1016/j.jdermsci.2021.11.003
  • Peer Reviewed
• [Journal Article] A Case of Possible Concurrence of Dermatitis Herpetiformis and Linear Immunoglobulin A / Immunoglobulin G Bullous Dermatosis. (2021)
  • Author(s): Minakawa S, Matsuzaki Y, Hashimoto T, Ishii N, Nishie W, Sawamura D.
  • Journal Title: Acta Dermatovenerol Croat. Volume: 29 Pages: 116-117
  • Peer Reviewed