Evolving models of the immunopathogenesis of T cell-mediated drug allergy: The role of host, pathogens, and drug response.
Evolving models of the immunopathogenesis of T cell-mediated drug allergy: The role of host, pathogens, and drug response.
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DOI：
10.1016/j.jaci.2015.05.050
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发表时间：
2015-08
期刊：
影响因子：
--
通讯作者：
Phillips EJ
中科院分区：
文献类型：
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作者：
White KD;Chung WH;Hung SI;Mallal S;Phillips EJ
免疫介导的药物不良反应（IM-ADR）是一个未被充分认识的可预防的发病率，死亡率和成本的来源。HLA基因座的遗传变异越来越多地与严重反应的风险相关，突出了T细胞免疫应答在B细胞介导和原发性T细胞介导的IM-ADR机制中的重要性。在这篇综述中，我们总结了宿主遗传学，微生物和药物在IM-ADR发展中的作用，扩展了现有的IM-ADR发病机制模型，以解决多个无法解释的观察结果，讨论这项工作在今天的临床实践中的意义，并描述了临床前药物毒性筛选，药物设计和开发的未来应用。
Immune-mediated adverse drug reactions (IM-ADRs) are an underrecognized source of preventable morbidity, mortality, and cost. Increasingly, genetic variation in the HLA loci is associated with risk of severe reactions, highlighting the importance of T-cell immune responses in the mechanisms of both B-cell mediated and primary T-cell mediated IM-ADRs. In this review, we summarize the role of host genetics, microbes and drugs in the development of IM-ADRs, expand upon the existing models of IM-ADR pathogenesis to address multiple unexplained observations, discuss the implications of this work in clinical practice today, and describe future applications for pre-clinical drug toxicity screening, drug design, and development.