Regulation of HLA expression on grafts to control refractory antibody-mediated rejection and elucidation of immune response to inducible HLA

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K22965
• 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: Aichi Medical University
• Principal Investigator: Maenaka Akihiro 愛知医科大学, その他部局等, 薬剤師 (80886193)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: 臓器移植 / 拒絶反応 / HLA / 免疫抑制剤

Outline of Final Research Achievements

While current organ transplantation has good short-term results, in the chronic phase, de novo donor specific HLA antibody(de novo DSA), especially against HLA-class II, resulting in a poor prognosis and that is a challenge to be overcome.Within this research period, we identified two existing drugs in clinical use that reduce the expression of HLA-class II on endothelial cells that assuming in an inflammatory state. We also found proteins that may be involved in HLA regulation. In addition, they found that one drug suppressed reactions that could progress to rejection involving cytotoxic T cells(CD8 T cells). We hope that these effects will lead to research that will serve as a basis for drug selection after transplantation.

Free Research Field

臓器移植

Academic Significance and Societal Importance of the Research Achievements

現在、内皮細胞におけるMHC(HLA)-class IIの発現・分解メカニズムの知見は乏しい。また、移植後新規に発生した抗体による拒絶反応(ABMR)に対する既存の治療は、主にレシピエント免疫系を標的とした中で、その効果は限定的なものに留まっている。本研究成果は、ドナー抗原であるHLA-DRの発現量の減少という新たなアプローチによるABMR制御だけでなく、細胞障害性T細胞が引き起こす拒絶反応(TCMR)、またHLA-class IIの発現に関わる可能性のあるタンパク質を見出した。これらの結果は、DSA産生時の検査・薬剤選択だけでなく、内皮細胞のHLAに知見を拡げることに繋がると考えている。