Elucidation of the onset mechanism of abacavir-induced severe skin reaction using humanized model animal

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K14995
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: Chiba University
• Principal Investigator: Ito Kousei 千葉大学, 大学院薬学研究院, 教授 (30323405)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: HLA / 特異体質毒性

Outline of Final Research Achievements

There was no suitable animal model to reproduce the idiosyncratic toxicity related to HLA polymorphism. In order to reproduce the rash caused by abacavir (ABC) seen in HLA-B*57:01 polymorphic carriers, mice introduced with HLA-B*57:01 or its negative control (HLA-B*57:03 polymorphism) were prepared. ABC was applied to their skin in vivo or to their primary cultured keratinocytes in vitro to investigate specific immune response. As a result, increase in lymph node weight in vivo and acute induction of inflammatory cytokines in vitro were selectively observed only in B*57:01 mice group. Idiosyncratic immune response related to HLA polymorphism was reproduced for the first time in our transgenic mice model, and the possibility that HLA polymorphism-dependent acute cellular response might be involved in tissue-specific drug toxicity.

Free Research Field

医薬品安全性学