Novel diagnostic assay for drug hypersensitivity by using basophils

• Project/Area Number: 17K10208
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Mie University
• Principal Investigator: Kakeda Masato 三重大学, 医学系研究科, リサーチアソシエイト (00422866)
• Co-Investigator(Kenkyū-buntansha): 水谷 仁 三重大学, 医学部, 非常勤講師 (30115737) ; 山中 恵一 三重大学, 医学系研究科, 教授 (70314135)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 好塩基球 / 薬疹

Outline of Final Research Achievements

In this study, Basophil activation test (BAT) and Drug lymphocyte stimulation test (DLST) were performed in patients with various types of drug hypersensitivity and food allergy. The high sensitivity was detected with both BAT and DLST in severe cutaneous drug reaction such as SJS/TEN and DIHS. Some samples showed positive results for BAT despite negative for DLST. As a result, our results showed BAT is a possible diagnostic assay for drug hypersensitivity and food allergy.

Academic Significance and Societal Importance of the Research Achievements

薬疹は時に生命に関わるほか、重篤な合併症や後遺症をきたすことがあり、正確な対応、そしてその被疑薬剤の同定が臨床上最重要であるが、現在臨床で用いられている各種被疑薬剤同定法にはそれぞれ一長一短がある。我々の研究結果はDLSTと比し少量の採血で可能な好塩基球活性化試験(BAT)が、薬疹の新たな被疑薬剤同定法としての可能性を示した。今後、BATが薬疹被疑薬同定法として健康保険適応となるべく研究を継続したいと考えている。

Research Products

• [Journal Article] Elevated plasma D-dimer levels in dermatomyositis patients with cutaneous manifestations (2019)
  • Author(s): Habe K, Higashiyama A, Akeda T, Mori R, Kakeda M, Yamanaka K, Mizutani H
  • Journal Title: Scientific Reports Volume: 5 Issue: 1 Pages: 1410-1410
  • DOI: 10.1038/s41598-018-38108-y
  • Peer Reviewed / Open Access
• [Journal Article] Infantile bullous pemphigoid successfully treated with i.v. immunoglobulin and cyclosporin (2019)
  • Author(s): Okada K, Kakeda M, Yamamoto S, Yokoyama T, Habe K, Nakato D, Hirayama M, Mizutani H, Yamanaka K
  • Journal Title: The Journal of Dermatology Volume: 46 Issue: 6 Pages: 213-214
  • DOI: 10.1111/1346-8138.14726
  • Peer Reviewed
• [Journal Article] Strong correlation between cancer progression and anti-transcription intermediary factor 1γ antibodies in dermatomyositis patients. (2018)
  • Author(s): Ogawa-Momohara M, Muro Y, Mitsuma T, Katayama M, Yanaba K, Nara M, Kakeda M, Kono M, Akiyama M.
  • Journal Title: Clin Exp Rheumatol Volume: 36 Pages: 990-995
  • Peer Reviewed
• [Journal Article] The Plasma Levels of ADAMTS-13, von Willebrand Factor, VWFpp, and Fibrin-Related Markers in Patients With Systemic Sclerosis Having Thrombosis (2017)
  • Author(s): Habe K, Wada H, Higashiyama A, Akeda T, Tsuda K, Mori R, Kakeda M, Matsumoto T, Ohishi K, Yamanaka K, Katayama N, Mizutani H.
  • Journal Title: Clin Appl Thromb Hemost Volume: 23 Issue: 6 Pages: 622-630
  • DOI: 10.1177/1076029617736382
  • Peer Reviewed / Int'l Joint Research
• [Presentation] 薬剤性過敏症症候群(DIHS)の7例 (2019)
  • Author(s): 欠田成人 水谷健人 刑部全晃 波部幸司 山中恵一
  • Organizer: 第1回アレルギー学会東海地方会
• [Presentation] DIHSの7例 (2019)
  • Author(s): 欠田成人 水谷健人 刑部全晃 波部幸司 山中恵一
  • Organizer: 第35回三重県アレルギー研究会
• [Presentation] サラゾスルファピリジンによるDIHSの3例 (2018)
  • Author(s): 欠田成人 山本晋也 市川彩夏 戸澤貴久 飯田祥平 水谷健人 刑部全晃 後藤啓元 波部幸司 山中恵一
  • Organizer: 第48回日本皮膚免疫アレルギー学会
• [Presentation] HLA-B*1301保有者に生じたサラゾスルファピリジンによる薬剤性過敏症症候群(DIHS)の2例 (2018)
  • Author(s): 欠田成人 刑部全晃 戸澤貴久 飯田祥平 水谷健人 後藤啓元 波部幸司 山中恵一
  • Organizer: 第67回日本アレルギー学会学術大会
• [Presentation] HLA-B*1301-Positive two cases of salazosulfapyridine-induced drug induced hypersensitivity syndrome (DIHS)/ drug reaction with eosinophilia and systemic symptoms (DRESS) (2018)
  • Author(s): Masato Kakeda, Masaaki Gyobu, Takahisa Tozawa, Shouhei Iida, Hiroyuki Goto, Koji Habe, and Keiichi Yamanaka
  • Organizer: EAACI DHM2018 Drug Hypersensitivity Meeting