Anti-complement component C5 prevent antibody-mediated rejection after lung transplantation in murine orthotopic model.

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K16410
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55040:Respiratory surgery-related
• Research Institution: Chiba University
• Principal Investigator: Shiina Yuki 千葉大学, 医学部附属病院, 医員 (30782304)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: 肺移植 / 拒絶反応 / 抗体関連拒絶 / 補体

Outline of Final Research Achievements

We aimed to establish the mice model of antibody-mediated rejection (AMR) after lung transplant and verify the efficacy of anti-C5 to AMR after lung transplant.
First, we performed lung transplants using BALB/c (major histocompatibility complex; MHC H2d) as a donor and C57BL/6 (MHC H2b) as a recipient. The recipient showed clinical features of AMR, and pre-sensitization by skin transplant enhanced AMR. Continuously, other mice underwent skin and lung transplants and treated with anti-C5 or with isotype IgG control. The mice treated with anti-C5 showed significantly lower acute rejection scores compared to the mice with isotype control. Among this model, Anti- C5 suppressed the AMR findings. Anti-C5 therapy may be effective for AMR in lung transplants.

Free Research Field

肺移植

Academic Significance and Societal Importance of the Research Achievements

今回の研究において、マウスモデルにおいてanti-C5抗体がAMRを抑制する可能性が示唆された。腎移植など他臓器の移植においては、anti-C5抗体は複数の臨床試験が行われるなどAMRに対する治療効果が期待されている。一方で肺移植後AMRに対するanti-C5抗体の効果を検証した報告は少なく、今回の研究は有効な治療選択肢の乏しい肺移植後AMRに対する新規治療法としてのanti-C5抗体の有用性を示す点で学術的意義のあるものと考える。今後、さらなる基礎実験・臨床試験の実施が望ましい。