| Project/Area Number |
18K16410
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 55040:Respiratory surgery-related
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| Research Institution | Chiba University |
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Principal Investigator |
Shiina Yuki 千葉大学, 医学部附属病院, 医員 (30782304)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 肺移植 / 拒絶反応 / 抗体関連拒絶 / 補体 / 補体阻害薬 |
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| 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.
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| 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。
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