Immunoprofiling of donor-specific antibody production by humanized mice and personalized medicine

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08632
• 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: Aichi Medical University
• Principal Investigator: NODA TAKAYUKI 愛知医科大学, 大学病院, 薬剤師 (50817088)
• Co-Investigator(Kenkyū-buntansha): 岩崎 研太 愛知医科大学, 医学部, 准教授 (10508881) ; 小林 孝彰 愛知医科大学, 医学部, 教授 (70314010)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: HLA / ヒト化マウス / B細胞

Outline of Final Research Achievements

In this study, we generated an HLA antibody-producing humanized mouse model and analyzed DSA-producing B cells for suppression of chronic antibody type-related rejection. The presence of memory cells was considered important because the same antibodies were detected in the patient cells as in the blood. Furthermore, removal of naive T cells was effective in suppressing the development of GVHD. However, antibody production in healthy human cells is not stable, and a mouse model has not yet been established.

Free Research Field

移植免疫

Academic Significance and Societal Importance of the Research Achievements

臓器移植における拒絶反応は、主にＴ細胞が関連する細胞性の拒絶反応と、B細胞が関連する抗体関連型拒絶反応（Antibody-Mediated Rejection: ABMR）の二つが存在する。免疫抑制剤の進歩により細胞性拒絶反応の制御がほぼ可能となった現在、ABMRの克服が臨床的に重要な課題となっている。中でもde novo のドナー特異的抗HLA抗体(Donor Specific HLA Antibody: DSA)産生を引き金とする慢性抗体関連型拒絶反応（Chronic ABMR: CAMR）に対する有効な予防法・治療法は確立されていない。