Investigation of the pathogenic mechanisms of clozapine-induced agranulocytosis
| Project/Area Number |
18K15497
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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 52030:Psychiatry-related
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| Research Institution | Fujita Health University |
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Principal Investigator |
Takeo Saito 藤田医科大学, 医学部, 講師 (30767611)
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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: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 薬理ゲノム学 / クロザピン / 無顆粒球症 / 顆粒球減少症 / ファーマコゲノミクス / バイオマーカー / 精神科 / ゲノム |
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| Outline of Final Research Achievements |
Clozapine-induced agranulocytosis (CIA)/clozapine-induced granulocytopenia (CIG) (CIAG) is a life- threatening event for schizophrenic subjects treated with clozapine. To date, the pathogenic mechanisms of CIAG remain largely unknown. Recent studies suggested immune-mediated mechanisms were involved in CIAG. Therefore, we evaluated the clozapine-induced lymphocyte proliferation using peripheral blood mononuclear cells of CIA patients to determine whether T-cell-mediated allergic reactions were involved in the pathogenesis of CIA. We compared the lymphocyte proliferation between CIA and tolerant control patients. The lymphocyte proliferation of CIA patients was increased compared with that of tolerant control patients. Although our results suggested immune-mediated mechanisms were involved in CIA, further investigations using more cases are warranted to ascertain this trend in clozapine-induced lymphocyte proliferation in CIA.
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| Academic Significance and Societal Importance of the Research Achievements |
HLA-B*59:01がクロザピン誘発性無顆粒球症において、大きな効果量を持つ確実なリスクであることが再確認されたこと、クロザピン誘発性無顆粒球症の発症において、免疫学的な発症機序の関与が示唆されたことは、クロザピン誘発性無顆粒球症の発症を防ぐ方法を確立するための足がかりになると考えらえる。発症の予防手段が確立されれば、クロザピン治療の安全性が増すことにより、医師と患者がクロザピン導入を積極的に受け入れるようになり、患者の早期回復、社会復帰につながると考えられる。
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Report
(3 results)
Research Products
(7 results)
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[Journal Article] Genome-Wide Association Study Detected Novel Susceptibility Genes for Schizophrenia and Shared Trans-Populations/Diseases Genetic Effect2018
Author(s)
Ikeda M,Takahashi A,Kamatani Y,Momozawa Y,Saito T,Kondo K,Shimasaki A,Kawase K,Sakusabe T,Iwayama Y,Toyota T,Wakuda T,Kikuchi M,Kanahara N,Yamamori H,Yasuda Y,Watanabe Y,Hoya S,Aleksic B,Kushima I,Arai H,Takaki M,Hattori K,Kunugi H,Okahisa Y,Ohnuma T,Ozaki N,Someya T,Hashimoto R,Yoshikawa T,Kubo M,Iwata N
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Journal Title
Schizophrenia Bulletin
Volume: 印刷中
Issue: 4
Pages: 824-834
DOI
Related Report
Peer Reviewed / Open Access
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