2023 Fiscal Year Final Research Report

Development of immunomonitoring system that predicts chronic antibody-mediated rejection in kidney transplant recipients

Research Project

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Project/Area Number	21K09389
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 56030:Urology-related
Research Institution	Hokkaido University
Principal Investigator	Hotta Kiyohiko 北海道大学, 大学病院, 講師 (90443936)
Co-Investigator(Kenkyū-buntansha)	村上正晃北海道大学, 遺伝子病制御研究所, 教授 (00250514) 田邉起北海道大学, 大学病院, 助教 (80880096) 篠原信雄北海道大学, 医学研究院, 教授 (90250422)
Project Period (FY)	2021-04-01 – 2024-03-31
Keywords	移植免疫 / 腎移植 / 慢性抗体関連型拒絶反応 / ドナー特異的抗体 / 早期診断 / リンパ球混合反応 / Tリンパ球 / ドナー特異的反応抑制
Outline of Final Research Achievements	Chronic active antibody-mediated rejection (CAAMR) induced by Donor-specific antibodies (DSAs) are the main cause of graft loss over time. We analyzed the T-cell alloantigen response via the DP in kidney recipients with DSAs (DSA+) or without DSAs (DSA－). A mixed lymphocyte reaction assay was implemented to assess the DP response. DSA+ patients showed significantly higher CD8+ and CD4+ T cell responses to donor cells than DSA－ patients. Furthermore, proliferating CD4+ T cells showed a marked increase in Th1 and Th17 responses in DSA+ patients than in DSA－ patients. In a comparison between anti-donor and third-party responses, the anti-donor CD4+ T cell response was significantly lower than the anti-third-party response. In contrast, the donor-specific hyporesponsiveness was absent in DSA+ patients. Our study demonstrated that DSA+ recipients have a greater potential for developing immune responses against the donor tissues via the DP.
Free Research Field	移植免疫学、腎移植
Academic Significance and Societal Importance of the Research Achievements	本研究で開発したMLR試験は、これまで存在しなかったCAAMR早期診断法となり得る可能性を持つと思われる。そして、CAAMRの早期診断は、CAAMRが形成される前の治療介入を可能とし、CAAMR発症を予防または遅らせることができる可能性がある。さらに、未だ正確な発症機序が不明なCAAMRにおいて、CAAMRを引き起こすDSAが直接認識経路を介したドナーに対するCD4+ T cell、Th1、Th17の活性化に関与していることを示し、CAAMRの病態の解明に寄与する可能性がある。