Elucidation of the Mechanism of Rejection after Liver Transplantation by Epitope Analysis of HLA

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K22950
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0905:Surgery of the organs maintaining homeostasis and related fields
• Research Institution: Kyoto University
• Principal Investigator: Yao Siyuan 京都大学, 医学研究科, 客員研究員 (70881944)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: HLA / 生体肝移植 / 抗体関連拒絶 / donor specific antigen

Outline of Final Research Achievements

Based on the liver transplant database, we retrospectively examined the correlation between HLA epitope matching between donors and recipients, and DSA incidence. The incidence of DSA gradually increased with years of transplantation. The fibrosis of the liver graft also progressed slowly over a long period of time. This study reaffirmed the strong need for prevention of DSA and development of therapeutic strategies for antibody-mediated rejection.
The number of mismatched HLA epitopes correlated with the occurrence of DSA. However, there were cases in which DSA did not occur even though the epitope mismatched load was high, and cases in which DSA did occur even though the epitope mismatched load was low.

Free Research Field

肝移植

Academic Significance and Societal Importance of the Research Achievements

臓器移植後の拒絶、特にドナー特異的抗体（donor-specific antibody: DSA）を伴う抗体関連拒絶は今も難治である。HLAエピトープ多型という新規バイオマーカーに基づき肝移植後の拒絶（特に抗体関連拒絶）を予測し、各移植における免疫抑制療法の強化・減量に有用な情報を現場に提供する。複数のドナー・レシピエント候補の中からハイリスク症例の回避にもつながる。それによって拒絶反応や合併症の危険性が軽減され、移植患者の生命予後のみならずQOLが向上すると期待できる。