Clinical Application of B Cell Lineage Markers for Assessing Sensitization in Kidney Transplant Recipients

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K09587
• 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: Osaka University (2023); Osaka General Medical Center (2020-2022)
• Principal Investigator: Kakuta Yoichi 大阪大学, 大学院医学系研究科, 講師 (40710116)
• Co-Investigator(Kenkyū-buntansha): 奥見 雅由 京都府立医科大学, 医学(系)研究科(研究院), 准教授 (60512978)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 腎移植 / 抗体関連型拒絶反応 / 脱感作療法 / 感作 / メモリーB細胞

Outline of Final Research Achievements

Donor-specific antibodies (DSA) are produced after recipients are sensitized. Performing a kidney transplant in this condition significantly increases the risk of graft failure. We have demonstrated using a rat antibody-mediated rejection (ABMR) model that sensitization induces donor-reactive memory B cells (DMBC), which differentiate into short-lived plasma cells after transplantation, leading to the production of DSA. Furthermore, in human samples, recipients that remained DMBC positive after desensitization therapy were found to have an increased risk of ABMR, independent of DSA, establishing DMBC as a separate risk factor for ABMR. This finding allows for a more detailed assessment of the effectiveness of desensitization therapy.

Free Research Field

泌尿器科

Academic Significance and Societal Importance of the Research Achievements

2019年からDSA陽性腎移植の脱感作療法に対する免疫グロブリンの使用が保険収載された。これによって、従来は禁忌とされていたハイリスクな腎移植が施行可能となった。しかし、経過が良好であってもDSA陽性が持続したり、病理学的にABMRを認める症例が多い。本研究の結果は、この原因を解き明かし、より最適な脱感作療法を確立するために有用であると考えられた。