Development of new treatments for IgG4-related disease aimed at precision medicine

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08770
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: The University of Tokyo
• Principal Investigator: Yamamoto Motohisa 東京大学, 医科学研究所, 准教授 (80404599)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: IgG4関連疾患 / 機械学習 / RNA-Seq / マイクロバイオーム / HLA / 治療反応性

Outline of Final Research Achievements

This study was carried out to elucidate the pathogenesis of IgG4-related disease for the purpose of personalized medicine. RNA-Seq analysis of sialoadenitis revealed that B-cell receptors and specific cytokine signaling are at the core of the pathogenesis. Exosome analysis revealed that serum miR-125a-3p and miR-125b-1-3p concentrations were significantly elevated and six genes were targeted. This finding may provide new insights for the future development of novel therapies. In addition, by utilizing registry data and artificial intelligence, a non-invasive diagnostic method with extremely good accuracy was successfully developed. It is suggested that in the future, a database including targetrd genes and microRNAs will be constructed and artificial intelligence will lead to the promotion of personalized medicine.

Free Research Field

膠原病・リウマチ内科学、臨床免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究は、個別化医療を目指したIgG4関連疾患の病態解明を目的に遂行した。顎下腺炎組織のRNA-Seq解析では、B細胞受容体や特定のサイトカインシグナルが病態の中心となることが判明した。エクソソーム解析では、血清miR-125a-3p、miR-125b-1-3p濃度が有意に上昇し、6つの遺伝子を標的としていることが明らかになった。今後の新規治療法の開発に新たな示唆を与えるものであると考えられる。またレジストリデータとAIを活用して、精度の極めて良好な非侵襲的な診断法の開発に成功した。今後、標的遺伝子、マイクロRNAを含めたデータベースを構築し、AIにより個別化医療の推進につながると示唆される。