Investigation for pathogenesis of cutaneous severe adverse drug reaction.

• Project/Area Number: 24390275
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Hokkaido University
• Principal Investigator: ABE Riichiro 北海道大学, 医学(系)研究科(研究院), 准教授 (60344511)
• Co-Investigator(Kenkyū-buntansha): FUJITA Yasuyuki 北海道大学, 北海道大学病院, 助教 (80374437)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000); Fiscal Year 2014: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2013: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
• Keywords: 薬疹 / アレルギー / 重症薬疹 / モデルマウス / 細胞死

Outline of Final Research Achievements

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening, cutaneous adverse drug reactions that are accompanied by keratinocyte cell death. Dead keratinocytes from SJS/TEN lesions exhibited necrosis, bymorphological criteria. We identified annexin A1 as a key mediator of keratinocyte death via formyl peptide receptor 1 (FPR1). Our results demonstrate that a necroptosis pathway, likely mediated by annexin 1 acting through the FPR1 receptor, contributes to SJS/TEN.

Research Products

• [Journal Article] An annexin A1-FPR1 interaction contributes to necroptosis of keratinocytes in severe cutaneous adverse drug reactions. (2014)
  • Author(s): Saito N, Qiao H, Yanagi T, Shinkuma S, Nishimura K, Suto A, Fujita Y, Suzuki S, Nomura T, Nakamura H, Nagao K, Obuse C, Shimizu H, Abe R.
  • Journal Title: Sci Transl Med. Volume: 6 Pages: 245-295
  • DOI: 10.1126/scitranslmed.3008227
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Disturbed balance in three subpopulations of CD4(+)Foxp3(+) regulatory T cells in Stevens-Johnson syndrome and toxic epidermal necrolysis patients. (2013)
  • Author(s): Yoshioka N, Suto A, Abe R, Saito N, Murata J, Hayashi-Ujiie I, Hoshina D, Fujita Y, Shimizu H.
  • Journal Title: Clinical Immunology Volume: 148 Pages: 89-91
  • DOI: 10.1016/j.clim.2013.04.002
  • Peer Reviewed
• [Journal Article] Stevens-Johnson syndrome/toxic epidermal necrolysis mouse model generated by using PBMCs and the skin of patients. (2013)
  • Author(s): Saito N, Yoshioka N, Abe R, Qiao H, Fujita Y, Hoshina D, Suto A, Kase S, Kitaichi N, Ozaki M, Shimizu H.
  • Journal Title: J Allergy Clin Immunol Volume: 131 Pages: 434-441
  • DOI: 10.1016/j.jaci.2012.09.014
  • Peer Reviewed
• [Presentation] 薬疹を理解するための免疫学. (2012)
  • Author(s): 阿部理一郎
  • Organizer: 第111回日本皮膚科学会総会
  • Place of Presentation: 京都国際会館(京都)
  • Year and Date: 2012-06-01