A multifaceted approach to HLA antibody-producing B cells for donor-specific antibody (DSA) regulation

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08584
• 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, その他部局等, 薬剤師 (50817088)
• Co-Investigator(Kenkyū-buntansha): 小林 孝彰 愛知医科大学, 医学部, 教授 (70314010) ; 岩崎 研太 愛知医科大学, 医学部, 准教授 (10508881)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 臓器移植 / DSA / ヒト化マウス

Outline of Final Research Achievements

The aim of this study is to establish a method for monitoring donor-specific anti-HLA (DSA) antibodies after transplantation that enables early diagnosis of chronic rejection. Detection of antibodies in the culture system was clearer than in serum. This method was found to be more advantageous for early diagnosis in some patients than in serum. We started to create a humanized mouse model of HLA antibody production to analyze DSA-producing B cells in the human body. However, model mice have yet to be established due to the lack of stability in antibody production.

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。