Investigation of the pathogenic mechanisms of clozapine-induced agranulocytosis

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K15497
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52030:Psychiatry-related
• Research Institution: Fujita Health University
• Principal Investigator: Takeo Saito 藤田医科大学, 医学部, 講師 (30767611)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: 薬理ゲノム学 / クロザピン / 無顆粒球症 / 顆粒球減少症

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.

Free Research Field

精神科遺伝学

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。