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Elucidation of specific cell death mechanism and biomarker search in severe drug eruption

Research Project

Project/Area Number 18H04047
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Review Section Medium-sized Section 53:Organ-based internal medicine and related fields
Research InstitutionNiigata University

Principal Investigator

Riichiro Abe  新潟大学, 医歯学系, 教授 (60344511)

Co-Investigator(Kenkyū-buntansha) 新熊 悟  奈良県立医科大学, 医学部, 准教授 (00613788)
小澤 岳昌  東京大学, 大学院理学系研究科(理学部), 教授 (40302806)
朝長 毅  国立研究開発法人医薬基盤・健康・栄養研究所, 医薬基盤研究所 創薬デザイン研究センター, 上級研究員 (80227644)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥44,720,000 (Direct Cost: ¥34,400,000、Indirect Cost: ¥10,320,000)
Fiscal Year 2020: ¥12,870,000 (Direct Cost: ¥9,900,000、Indirect Cost: ¥2,970,000)
Fiscal Year 2019: ¥12,870,000 (Direct Cost: ¥9,900,000、Indirect Cost: ¥2,970,000)
Fiscal Year 2018: ¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000)
Keywords重症薬疹 / 細胞死 / Stevens-Johnson症候群 / 中毒性表皮壊死症 / 薬疹 / 感受性遺伝子
Outline of Final Research Achievements

We elucidated and identified (A) the mechanism of epidermal cell necrosis, (B) the mechanism of inducing immune response to drugs, and (C) the onset susceptibility factor in severe drug eruption, and elucidated and identified the mechanism of onset of severe drug eruption. Reveal the whole picture of. Furthermore, using the obtained results, we identified biomarkers that are targets for diagnosis and treatment, established diagnostic methods, and developed new therapeutic agents. (A) We identified biomarkers such as galectin-7 and elucidated disease-specific mechanisms of other cellular mechanisms (ferrotopsis, etc.). (B) The specific pathogenic mechanism of the factors obtained in (A) was elucidated. (C) We developed a therapeutic drug for severe drug eruption targeting biomarkers and identified candidate compounds.

Academic Significance and Societal Importance of the Research Achievements

重症薬疹であるスティーヴンス・ジョンソン症候群(SJS)及び中毒性表皮壊死症(TEN)は、全身の皮膚多形紅斑、粘膜傷害と発熱を伴う、未だに致死率の高い重篤な疾患である。SJS/TENでは、表皮細胞の細胞死を特徴とするが、私たちはこの細胞死機序の解明を主に行った。
これまで知られていなかった新規の細胞死によっておこること、さらにその詳細な機序を解明した。さらにこの機序も用いて、細胞死を阻害する薬剤の開発を行っている。
新しい重症薬疹の治療薬が会へ津できれば、医療において安心安全や薬剤使用を行うことが出来る。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (12 results)

All 2021 2020 2019 2018

All Journal Article (7 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 7 results) Presentation (5 results) (of which Int'l Joint Research: 2 results,  Invited: 4 results)

  • [Journal Article] Supportive care in the acute phase of Stevens?Johnson syndrome and toxic epidermal necrolysis: an international, multidisciplinary Delphi‐based consensus2021

    • Author(s)
      Brggen M.‐C.、Le S.T.、Walsh S.、Toussi A.、Prost N.、Ranki A.、Didona B.、Colin A.、Horv?th B.、Brezinova E.、Milpied B.、Moss C.、Bodemer C.、Meyersburg D.、Salavastru C.、Tiplica G.‐S.、Howard E.、Bequignon E.、Bouwes Bavinck J.N.、Newman J.、Gueudry J.、N?geli M.、Zaghbib K.、Hama N.、Abe R
    • Journal Title

      British Journal of Dermatology

      Volume: in press Issue: 3 Pages: 616-626

    • DOI

      10.1111/bjd.19893

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Plasma exosomal miR-375-3p regulates mitochondria-dependent keratinocyte apoptosis by targeting XIAP in severe drug-induced skin reactions2020

    • Author(s)
      Zhang Chen、Zhu ZhenLai、Gao JiXin、Yang LuTing、Dang ErLe、Fang Hui、Shao Shuai、Zhang ShaoLong、Xiao ChunYing、Yuan Xu、Li Wei、Abe Riichiro、Qiao HongJiang、Wang Gang、Fu Meng
    • Journal Title

      Science Translational Medicine

      Volume: 12 Issue: 574 Pages: 6142-6142

    • DOI

      10.1126/scitranslmed.aaw6142

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Characteristic pathological features of keratinocyte death in a case of Stevens?Johnson syndrome manifested by an immune checkpoint inhibitor2020

    • Author(s)
      Kimura H.、Hasegawa A.、Takei I.、Kawai T.、Tsuchida Y.、Abe Y.、Hayashi R.、Hama N.、Abe R.
    • Journal Title

      Journal of the European Academy of Dermatology and Venereology

      Volume: 35 Issue: 2 Pages: 142-145

    • DOI

      10.1111/jdv.16872

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] RIP3 as a diagnostic and severity marker for Stevens-Johnson syndrome and toxic epidermal necrolysis2020

    • Author(s)
      Hasegawa Akito、Shinkuma Satoru、Hayashi Ryota、Hama Natsumi、Watanabe Hideaki、Kinoshita Manao、Ogawa Youichi、Abe Riichiro
    • Journal Title

      The Journal of Allergy and Clinical Immunology: In Practice

      Volume: 8 Issue: 5 Pages: 1768-1771

    • DOI

      10.1016/j.jaip.2020.01.006

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Galectin-7 as a potential biomarker of Stevens-Johnson syndrome/ toxic epidermal necrolysis: Identification by targeted proteomics using causative drug-exposed peripheral blood cells2019

    • Author(s)
      Natsumi Hama, Keiko Nishimura, Akito Hasegawa, Akihiko Yuki, Hideaki Kume, Jun Adachi, Manao Kinoshita, Youichi Ogawa, Saeko Nakajima, Takashi Nomura, Hideaki Watanabe, Yoshiko Mizukawa, Takeshi Tomonaga, Hiroshi Shimizu, Riichiro Abe
    • Journal Title

      J Allergy Clin Immunol Pract

      Volume: 印刷中 Issue: 8 Pages: 2894-2897

    • DOI

      10.1016/j.jaip.2019.05.002

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Culprit Drugs Induce Specific IL-36 Overexpression in Acute Generalized Exanthematous Pustulosis2019

    • Author(s)
      Meier-Schiesser Barbara、Feldmeyer Laurence、Jankovic Dragana、Mellett Mark、Satoh Takashi K.、Yerly Daniel、Navarini Alexander、Abe Riichiro、Yawalkar Nikhil、Chung Wen-Hung、French Lars E.、Contassot Emmanuel
    • Journal Title

      Journal of Investigative Dermatology

      Volume: 139 Issue: 4 Pages: 848-858

    • DOI

      10.1016/j.jid.2018.10.023

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Potential role of extracellular vesicle-meditated antigen presentation in Helicobacter pylori hypersensitivity during eradication therapy2018

    • Author(s)
      Ito T, Abe R, et al.
    • Journal Title

      J Allergy Clin Immunol

      Volume: 印刷中 Issue: 2 Pages: 672-676.e12

    • DOI

      10.1016/j.jaci.2018.02.046

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Recent topics of cutaneous adverse drug reactions: from microbiome to AI2020

    • Author(s)
      Abe R
    • Organizer
      Korean Dermatological Association
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Pathogenesis of SCAR: Necroptosis in Stevens-Johnson syndrome/ toxic epidermal necrolysis2020

    • Author(s)
      Abe R
    • Organizer
      JSAWAO Congress
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 重症薬疹の病態とバイオマーカー2019

    • Author(s)
      阿部理一郎
    • Organizer
      日本皮膚科学会東京東部合同支部総会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 薬疹のメカニズム2018

    • Author(s)
      阿部理一郎
    • Organizer
      日本皮膚科学会東京支部総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Role of exosome mediated antigen presentation in antibiotic related allergic reactions2018

    • Author(s)
      阿部理一郎
    • Organizer
      DHM2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited

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Published: 2018-04-23   Modified: 2022-01-27  

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