Research of the effects of DPP-4 inhibitor on the dysruption of self tolerance in bullous pemphigoid

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17334
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Hokkaido University
• Principal Investigator: Izumi Kentaro 北海道大学, 大学病院, 講師 (50793668)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 水疱性類天疱瘡 / 自己免疫疾患 / 17型コラーゲン / 自己抗体 / DPP-4阻害薬 / ELISA / 自己免疫寛容 / BP180

Outline of Final Research Achievements

Immunisation of BP180 humanised mice with full-length BP180 recombinant protein induced bullous pemphigoid-like skin lesions around the eyes and ears. The incidence and severity of skin lesions were compared between the DPP-4 inhibitor vildagliptin-treated and non-treated groups, but no significant differences were found between the groups. The induction rate and antibody titer of anti-BP180 antibodies produced by immunisation were also compared, but no significant differences were found between the groups. Detailed epitope mapping was performed to verify whether there were differences in the epitopes of the autoantibodies induced, and found that in the vildagliptin-treated group the autoantibody epitopes were confined to the extracellular region of BP180.

Free Research Field

皮膚科学

Academic Significance and Societal Importance of the Research Achievements

水疱性類天疱瘡は高齢者に好発する指定難病であるが、その詳細な発症機序はいまだ不明である。近年2型糖尿病治療のための本邦における第一選択薬であるDPP-4阻害薬投与に関連する水疱性類天疱瘡が問題となっている。本研究ではBP180に対する免疫寛容の破綻の際にDPP-4阻害薬の投与を行うことで非投与時と異なる免疫応答が生じる結果、誘導される自己抗体のエピトープに変化が生じる可能性があることが明らかとなった。本研究で得られた知見がDPP-4阻害薬関連水疱性類天疱瘡の発症機序の解明の一助になるとともに、より安全な2型糖尿病治療の遂行を実現可能にするためのさらなる研究の礎になることが期待される。