Development of novel treatment for fulminant myocarditis focusing on immune checkpoint molecules
Project/Area Number |
19K23843
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Research Category |
Grant-in-Aid for Research Activity Start-up
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Allocation Type | Multi-year Fund |
Review Section |
0803:Pathology, infection/immunology, and related fields
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Research Institution | Nagoya University |
Principal Investigator |
Hiraiwa Hiroaki 名古屋大学, 医学部附属病院 循環器内科, 病院助教 (10844904)
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Project Period (FY) |
2019-08-30 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
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Keywords | 劇症型心筋炎 / リンパ球性心筋炎 / 免疫チェックポイント分子 / PD-1, PD-L1 / 活性化T細胞 / 予後 / PD-1 PD-L1 / PD-1 reporter systemの構築 |
Outline of Research at the Start |
心筋炎は未だ救命率の低い致死的疾患であり予防・治療法の確立は社会的ニーズが高い。一方、その臨床像は幅広く、発症や劇症化に至るメカニズムについて詳細は明らかでないため、薬物治療も確立されていないのが現状である。本研究は免疫チェックポイント分子であるPD-1(Programmed cell death 1)およびPD-L1(Programmed cell death-ligand 1)の発現が心筋炎の発症や劇症化進展に関与しているかどうかを検証することで、心筋炎に対する免疫応答を介した特異的な治療法の開発へ繋げることを目指した研究である。
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Outline of Final Research Achievements |
This study investigated the relationship between T cell markers and PD-L1 expression in myocardial tissue and the prognosis of patients with fulminant lymphocytic myocarditis (FM). We analyzed 16 FM patients and found that the number of CD8+ T cells and CD8+/CD4+ T cell ratio were significantly higher in the group with cardiac events (composite of cardiac death and left ventricular assist device implantation). Additionally, the number of FoxP3+ T cells was higher in the cardiac event group, and PD-L1 expression in myocardial cells was also higher in the same group. Kaplan-Meier survival analysis revealed that high CD8+ T cell count or high PD-L1 expression in the myocardium could be poor prognostic factors in FM. Combining the expression of CD8+ T cells and PD-L1 could potentially help stratify the risk of cardiac events in FM. This study provides new insights into the mechanism and prognosis of fatal FM, which could aid in the development of new treatment strategies in the future.
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Academic Significance and Societal Importance of the Research Achievements |
リンパ球性劇症型心筋炎(FM)は致死的な疾患であり、劇症化メカニズムや治療開発に対する社会的ニーズが非常に高い。本研究では、T細胞プロファイルおよび免疫チェックポイント分子であるPD-1およびPD-L1の発現に注目した。結果、FM患者のうち、CD8陽性T細胞数およびCD8陽性/CD4陽性T細胞比が高い群で予後が悪いこと、PD-L1高発現群やCD8高値-PD-L1高発現群で生存率が低く、CD8陽性T細胞とPD-L1の発現を組み合わせることで、予後層別化が可能であることを示した。本研究の結果は、FM患者の予後を予測するための新たな知見を提供し、将来的に新たな治療戦略の開発に役立つことが期待される。
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Report
(5 results)
Research Products
(2 results)
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[Journal Article] Fulminant myocarditis with myositis of ocular and respiratory muscles2020
Author(s)
Hiraiwa H, Furusawa K, Kazama S, Kimura Y, Shibata N, Arao Y, Oishi H, Kato H, Kuwayama T, Yamaguchi S, Kondo T, Sawamura A, Morimoto R, Okumura T, Murohara T.
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Journal Title
Nagoya Journal of Medical Science
Volume: 82
Issue: 3
Pages: 585-593
DOI
NAID
ISSN
2186-3326
URL
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Fulminant Myocarditis with Myositis of Ocular and Respiratory Muscles: A Case Report2020
Author(s)
Hiroaki Hiraiwa, Kenji Furusawa, Shingo Kazama, Yuki Kimura, Naoki Shibata, Yoshihito Arao, Hideo Oishi, Hiroo Kato, Tasuku Kuwayama, Shogo Yamaguchi, Toru Kondo, Akinori Sawamura, Ryota Morimoto, Takahiro Okumura, Toyoaki Murohara
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Journal Title
Nagoya Journal of Medical Science
Volume: -
Related Report
Peer Reviewed