Determination of causative drugs using ex-vivo expanded skin infiltrating T cells in drug eruptions

• Project/Area Number: 16K10151
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: Fujiyama Toshiharu 浜松医科大学, 医学部附属病院, 講師 (60402301)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 薬疹 / 原因薬剤 / MDR1 / 重症薬疹

Outline of Final Research Achievements

It is not always easy to determine the causative drugs in drug eruption cases. We usually perform DLST, a conventional method to determine the causative drug using peripheral blood mononuclear cells. Suspicious drugs are added to the cells to measure the uptake of 3H-thymidine. However, the detection rate is not satisfactory. Therefor we tried to establish new methods to determine the causative drugs by using ex-vivo expanded skin infiltrating T cells.
We successfully determine the causative drugs in more than half of our cases of drug eruption.

Academic Significance and Societal Importance of the Research Achievements

再発予防の観点から、薬疹の原因薬剤の同定は非常に重要だが、既存の検査方法ではその陽性率が高くないことから、同定できないケースも多数存在する。既存の方法では同定できなくても、今回我々が開発した、皮膚浸潤T細胞を用いた手法により、同定できたケースも存在し、調べた過半数のケースで同定できたことから、有用な手法と考えられる。

Research Products

• [Presentation] Skin-Infiltrating MDR1-Expressing T Cells Are Associated With Therapeutic Responsiveness To Corticosteroids In Severe Cutaneous Adverse Reactions Of Drugs (2018)
  • Author(s): Toshiharu Fujiyama
  • Organizer: Drug Hypersensitivity Meeting
• [Presentation] 皮膚湿潤Ｔ細胞を用いたELISpot法で原因薬剤同定を試みたSJS/TEN (2016)
  • Author(s): 藤山俊晴
  • Organizer: 第46回日本皮膚アレルギー・接触皮膚炎学会総会学術大会．
  • Place of Presentation: 東京
  • Year and Date: 2016-11-05
• [Presentation] Novel lymphocyte stimulation tests using ex-vivo expanded skin-infiltrating T cells from severe drug eruptions. (2016)
  • Author(s): 藤山俊晴
  • Organizer: 46th Annual ESDR Meeting in 2016
  • Place of Presentation: Munich
  • Year and Date: 2016-09-09
  • Int'l Joint Research
• [Presentation] A novel method to determine causative drugs using ex-vivo expanded skin-infiltrating T cells from severe drug eruptions. (2016)
  • Author(s): 藤山俊晴
  • Organizer: 第65回日本アレルギー学会学術大会．
  • Place of Presentation: 東京
  • Year and Date: 2016-06-18
• [Presentation] Ex-Vivo Expanded Skin-Infiltrating T Cells From Severe Drug Eruptions Are Reactive With Causative Drugs: A Possible Novel Method For Determination Of Causative Drugs. (2016)
  • Author(s): 藤山俊晴
  • Organizer: 7th Drug Hypersensitivity Meeting
  • Place of Presentation: Malaga
  • Year and Date: 2016-04-20
  • Int'l Joint Research