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Analysis of drug-HLA binding structures in severe drug eruptions and development of drugs for severe drug eruptions

Research Project

Project/Area Number 18K08277
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53050:Dermatology-related
Research InstitutionShowa University

Principal Investigator

Watanabe Hideaki  昭和大学, 医学部, 教授 (80327931)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords重症型薬疹 / HLA / バイカリン / Annexin A1 / スティーヴンス・ジョンソン症候群 / 中毒性表皮壊死症 / 薬剤性過敏症症候群 / 重症薬疹 / Stevens-Johnson症候群 / 結合様式 / 薬剤抗原提示 / ドッキングモデル / 薬疹発症予測 / 薬疹治療薬開発 / ダプソン / ラモトリギン / Molecular structure / Docking simulation
Outline of Final Research Achievements

Several drugs with frequently reported drug eruptions were expected to cause severe drug eruptions in individuals with HLA-B*13:01 due to their common structure with aromatics and a double bonded oxygen near the aromatics.
We found that baicalin inhibits cell death by blocking the binding of Annexin A1 and FRP1, which are involved in cell death in severe drug eruption SJS/TEN, and inhibiting the activation of RIP1 and RIP3, and thus may be a candidate for the treatment of SJS.

Academic Significance and Societal Importance of the Research Achievements

薬剤を投与する前にHLAを測定することで死亡率の高いSJS/TEN(SJSで4%、TENで30%)の発症を抑える、いわゆるオーダーメード医療に繋がる。また現在SJS/TENの治療にはステロイド全身投与以外にいい治療法が無いのが現況であるが、漢方薬バイカリンが、SJS/TENにおいて皮膚の細胞死を阻害する可能性を見出し、SJSの治療薬の候補となりうることがわかり、今後の臨床応用に繋がる研究である。

Report

(4 results)
  • 2021 Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (4 results)

All 2019 2018

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results) Presentation (3 results)

  • [Journal Article] Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms due to lamotrigine differs from that due to other drugs2019

    • Author(s)
      Tashiro Yasuya、Azukizawa Hiroaki、Asada Hideo、Niihara Hiroyuki、Morita Eishin、Yamauchi Teruo、Mizukawa Yoshiko、Kusakabe Yoshio、Numazawa Satoshi、Izumi Miki、Sueki Hirohiko、Watanabe Hideaki
    • Journal Title

      The Journal of Dermatology

      Volume: 46 Issue: 3 Pages: 226

    • DOI

      10.1111/1346-8138.14776

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 重症薬疹における遺伝的背景2018

    • Author(s)
      渡辺秀晃
    • Organizer
      第48回日本皮膚免疫アレルギー学会総会学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 重症薬疹のトピックス(臨床)2018

    • Author(s)
      渡辺秀晃
    • Organizer
      第117回日本皮膚科学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] スティーヴンス・ジョンソン症候群(SJS). 中毒性表皮壊死症(TEN)ー診断と治療ー.2018

    • Author(s)
      渡辺秀晃
    • Organizer
      第70回日本皮膚西部支部学術学会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2023-12-25  

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