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Significance of gamma-chain in severe cutaneous adverse reactions

Research Project

Project/Area Number 19K17779
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 53050:Dermatology-related
Research InstitutionYokohama City University

Principal Investigator

WATANABE Yuko  横浜市立大学, 医学部, 講師 (10567605)

Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥130,000 (Direct Cost: ¥100,000、Indirect Cost: ¥30,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Keywords重症薬疹 / アレルギー / バイオマーカー / Stevens-Johnson 症候群 / 中毒性表皮壊死症 / γ-chain subunit / IL-2RG / Stevens-Johnson症候群 / 血清γ chain subunit / 血清γ-chain subunit / gamma-chain
Outline of Research at the Start

Stevens-Johnson syndrome (SJS)、 toxic epidermal necrolysis (TEN)は発熱とともに粘膜や皮膚にびらんを生じる致死的な重症薬疹である。Cytotoxic T細胞(CTL)やNK細胞による直接的な皮膚障害および細胞傷害因子の産生が、SJS/TENの病態を形成するとされるが、薬剤特異的反応のどの過程で細胞傷害因子が産生されるのか、なぜ皮膚障害を起こすのかなど、多くの点については解明されていない。本研究では、重症薬疹の病態に寄与する可能性のあるgammma-chain cytokineに着目し、SJS/TENの病態、治療応用への基盤を構築することを目的とする。

Outline of Final Research Achievements

This study examined the expression of γ-chain subunits in Stevens-Johnson syndrome (SJS) and toxic necrolysis (TEN). Serum γ-chain levels in SJS/TEN patients in the early stage of disease onset were significantly higher than those in the general drug eruption group and decreased during the recovery phase. Furthermore, serum γ-chain levels in SJS/TEN patients were correlated with severity of SJS/TEN, sequelae, and death.
When comparing serum and blister fluid in the same SJS/TEN patients, blister fluids were found to have higher γ-chain levels than serum. Immunostaining of the skin of SJS/TEN patients showed a significant enhancement of γ-chain expression in epidermal cells. Furthermore, in vitro experiments suggested that soluble γ-chain was involved in cell proliferation and apoptosis-related factors in human epidermal cells.

Academic Significance and Societal Importance of the Research Achievements

SJS/TENは重篤で急速進行性で致死的な皮膚粘膜疾患であるが、診断、病勢、予後を予測するバイオマーカーは確立していない。本研究によって、血清γ-chain値は病勢、予後を反映することが示され、新たなバイオマーカー候補としての可能性が示唆された。今後はさらに、SJS/TENの病態への関与について研究を行い、治療標的としての可能性を検討する。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (3 results)

All 2023 2021 2020

All Presentation (3 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results)

  • [Presentation] Increased levels of common γ-chain in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis reflect disease severity2023

    • Author(s)
      Yuko Watanabe, Noriko Ikeda, Yukie Yamaguchi
    • Organizer
      1st International Societies for Investigative Dermatology
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 重症薬疹の重症度に関わる因子の解析2021

    • Author(s)
      渡邉裕子
    • Organizer
      第120回日本皮膚科学会総会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] Expression of serum and skin γ-chain levels in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis2020

    • Author(s)
      Yuko Watanabe, Yukie Yamaguchi, Noriko Komitsu, Tomoya Watanabe, Michiko Aihara
    • Organizer
      The 45th Annual Meeting of the Japanese Society for Investigative Dermatology
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research

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Published: 2019-04-18   Modified: 2024-01-30  

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