免疫药理基因组学的应用：预测、预防和理解免疫介导的药物不良反应。
Applications of Immunopharmacogenomics: Predicting, Preventing, and Understanding Immune-Mediated Adverse Drug Reactions.
机构信息
Department of Pharmacy Practice and Science, University of Arizona College of Pharmacy, Tucson, Arizona 85721, USA.
Sarver Heart Center, University of Arizona College of Medicine, Tucson, Arizona 85724, USA.
出版信息
Annu Rev Pharmacol Toxicol. 2019 Jan 6;59:463-486. doi: 10.1146/annurev-pharmtox-010818-021818. Epub 2018 Aug 22.
Abstract
Adverse drug reactions (ADRs) are a significant health care burden. Immune-mediated adverse drug reactions (IM-ADRs) are responsible for one-fifth of ADRs but contribute a disproportionately high amount of that burden due to their severity. Variation in human leukocyte antigen ( HLA) genes has emerged as a potential preprescription screening strategy for the prevention of previously unpredictable IM-ADRs. Immunopharmacogenomics combines the disciplines of immunogenomics and pharmacogenomics and focuses on the effects of immune-specific variation on drug disposition and IM-ADRs. In this review, we present the latest evidence for HLA associations with IM-ADRs, ongoing research into biological mechanisms of IM-ADRs, and the translation of clinical actionable biomarkers for IM-ADRs, with a focus on T cell-mediated ADRs.
摘要
药物不良反应（ADRs）是一个重大的医疗负担。免疫介导的药物不良反应（IM-ADRs）占 ADRs 的五分之一，但由于其严重性，它们在该负担中所占比例过高。人类白细胞抗原（HLA）基因的变异已成为预防先前不可预测的 IM-ADRs 的潜在预处方筛选策略。免疫药物基因组学结合了免疫基因组学和药物基因组学的学科，重点关注免疫特异性变异对药物处置和 IM-ADRs 的影响。在这篇综述中，我们介绍了 HLA 与 IM-ADRs 相关的最新证据、正在进行的 IM-ADRs 生物学机制研究，以及 IM-ADRs 的临床可操作生物标志物的转化，重点是 T 细胞介导的 ADRs。
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