Approach to understanding of pathogenesis and invention of new treatments from the results of preliminary genetic studies

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09975
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Kyoto University
• Principal Investigator: Yoshifuji Hajime 京都大学, 医学研究科, 助教 (20422975)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 高安動脈炎 / iPS細胞 / IL-12

Outline of Final Research Achievements

Takayasu arteritis is a rare disease that affects large arteries, and often affects young women. An SNP in IL12B gene region has been found by genome-wide association study of Takayasu arteritis. IL12B gene encodes p40, which is a shared subunit of IL-12 and IL-23. We used peripheral blood mononuclear cells and iPS cells of patients with Takayasu arteritis and healthy controls, and examined the role of IL12B gene in the pathology of Takayasu arteritis. Supernatant p40 concentration was significantly higher in macrophages from patients with risk-type SNPs than in macrophages from patients without risk-type SNPs. Supernatant p40 concentration was higher in the disease-specific iPS cell-derived macrophages than in the control iPS cell-derived macrophages.

Free Research Field

膠原病学

Academic Significance and Societal Importance of the Research Achievements

高安動脈炎患者において、発症リスク型SNPの影響によりp40産生能が高くなり、ヘルパーT細胞の活性化を通して、血管炎病態を引き起こしている可能性が示唆された。2015年、著者らはp40を阻害する生物学的製剤ウステキヌマブを高安動脈炎患者3名に投与するパイロット試験を行い、症状・臨床データの改善を認めた（Terao, Scand J Rheum）。次段階となる臨床治験の論理的根拠を強化するために、本計画において、高安動脈炎患者検体や疾患特異的iPS細胞を用いた基礎実験を行った。今回得られた結果は、p40を標的とする高安動脈炎の新規治療薬開発につながることが示唆された。