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

• 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
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥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)
• Keywords: 肺移植 / 拒絶反応 / 抗体関連拒絶 / 補体 / 補体阻害薬

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.

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。

Research Products

• [Presentation] Development of novel murine antibody mediated rejection model after orthotopic lung transplant. (2019)
  • Author(s): Yuki Shiina, Hidemi Suzuki, akahiro Yamanaka, Jotaro Yusa, Jun Naito, Takahiro Ochi, Taisuke Kaiho, Kota Ohashi, Yuki Sata, Atsushi Hata, Takahide Toyoda, Takayoshi Yamamoto, Junichi Morimoto, Yuichi Sakairi, Hironobu Wada, Takahiro Nakajima, Ichiro Yoshino
  • Organizer: The International Society for Heart and Lung Transplantation 2019 Annual Meeting and Scientific Sessions
  • Int'l Joint Research
• [Presentation] 肺移植後抗体関連型拒絶反応に対するAnti-C5抗体の予防効果 (2019)
  • Author(s): 椎名裕樹，鈴木秀海，山中崇寛，由佐城太郎，内藤 潤，越智敬大，伊藤祐輝，海寶大輔，大橋康太，佐田諭己，畑 敦，豊田行英，山本高義，森本淳一，坂入祐一，和田啓伸，中島崇裕，吉野一郎
  • Organizer: 第36回日本呼吸器外科学会総会
• [Presentation] 移植肺に対する抗体関連型拒絶反応の機序解明に向けてのマウスモデルの確立 (2019)
  • Author(s): 椎名裕樹，鈴木秀海，山中崇寛，由佐城太郎，内藤潤，越智敬大，海寶大輔，大橋康太，佐田諭己，畑 敦，豊田行英，山本高義，森本淳一，坂入祐一，和田啓伸，中島崇裕，吉野一郎
  • Organizer: 第119回日本外科学会定期学術集会 抄録
• [Presentation] Development of novel murine antibody mediated rejection model after orthotopic lung transplant. (2019)
  • Author(s): Yuki Shiina, Hidemi Suzuki, Takahiro Yamanaka, Jotaro Yusa, Jun Naito, Takahiro Ochi, Taisuke Kaiho, Kota Ohashi, Yuki Sata, Atsushi Hata, Takahide Toyoda, Takayoshi Yamamoto, Junichi Morimoto, Yuichi Sakairi, Hironobu Wada, Takahiro Nakajima, Ichiro Yoshino
  • Organizer: The International Society for Heart and Lung Transplantation 2019 Annual Meeting and Scientific Sessions
  • Int'l Joint Research