Development of an immunological monitoring system to predict chronic rejection in kidney transplant recipients.

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K09156
• 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) ; 岩見 大基 北海道大学, 大学病院, その他 (80581115) ; 篠原 信雄 北海道大学, 医学研究院, 教授 (90250422)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 移植免疫 / 腎移植 / 慢性抗体関連型拒絶反応 / 早期診断 / Tリンパ球 / 長期成績 / リンパ球混合反応 / CD4陽性T細胞

Outline of Final Research Achievements

Chronic active antibody-mediated rejection (CAAMR) is the main cause of graft loss in the long-term. Pathological changes during CAAMR occur gradually even without clinical manifestations, followed by dysregulation of the function of the kidney transplant. Therefore, a reliable immunoresponse monitoring system to identify recipients who will develop CAAMR in the future is required.
A mixed lymphocyte reaction (MLR) assay is a method to measure T cells alloreactivity via direct pathway (DP). Recent studies indicate that DP also contribute the pathogenesis of chronic injury. However, there are no reports of MLR assay to monitor CAAMR. Therefore, we tried to develop a novel MLR monitoring system that predicts CAAMR in kidney transplant recipients. To this end, we measured the anti-donor response using our novel MLR in 150 kidney recipients whose graft status were evaluated by graft biopsy and analyzed the relationship between the anti-donor response and pathological findings of allograft.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

腎移植長期成績の向上にCAAMRの克服は必要不可欠である。有効な治療方法もないのが現状であるため、CAAMRとなりうる患者を未然にもしくは可能な限り早期に発見する診断法の開発が必要である。今回我々が開発した手法によりCAAMRの早期診断が可能になったことで、腎移植の長期成績の最大の問題が解決され長期成績の向上に寄与すると思われる。