Development of therapeutic methods of preserving regulatory B-cell function for antibody-mediated rejection.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08982
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Hiroshima University
• Principal Investigator: Ide Kentaro 広島大学, 病院(医), 講師 (50511565)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: molecular mismatch / 抗ドナーHLA抗体 / 一塩基多型 / 抗体関連型拒絶反応

Outline of Final Research Achievements

We analyzed the relationship between T-cell rejection (TCMR) and de novo donor-specific anti-HLA antibody (dnDSA) production and eplet mismatch (EpMM) in liver transplant recipients. We found that HLA-DQB1 EpMM count of 7 or higher was associated with an increased risk factor for TCMR, and an HLA-DQB1 EpMM count of 9 or higher was associated with an increased risk for dnDSA.
SNPs analysis of CXCR5 and CTLA-4 involved in follicular T cell (Tfh) differentiation in kidney transplant recipients revealed that both genotypes with increased Tfh cells are at increased risk for dnDSA production.

Free Research Field

臓器移植

Academic Significance and Societal Importance of the Research Achievements

CTLA-4の細胞外ドメインとヒトIgG1のFc部分との融合蛋白であるCTLA4-IgはCD80/86とCD28の相互作用を阻害することによりT細胞の活性化を抑制する作用がある。これまでCTLA4-Ig単剤では抗体関連型拒絶反応(AMR)の制御は不能であると報告されているがプロテアソーム阻害薬でDSA産生細胞を同時に抑制することにより、AMRが制御可能となる可能性がある。今後は、高感作マウスの移植モデルでTfh細胞とDSA産生細胞の制御により抗体関連型拒絶反応が克服可能か否か検証し、実臨床への応用を目指す