Applications of Immunopharmacogenomics: Predicting, Preventing, and Understanding Immune-Mediated Adverse Drug Reactions.,Annual Review of Pharmacology and Toxicology

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Applications of Immunopharmacogenomics: Predicting, Preventing, and Understanding Immune-Mediated Adverse Drug Reactions.
Annual Review of Pharmacology and Toxicology ( IF 11.2 ) Pub Date : 2018-08-22 , DOI: 10.1146/annurev-pharmtox-010818-021818
Jason H Karnes _{1,

2,

3} , Matthew A Miller ₁ , Katie D White ₄ , Katherine C Konvinse _{5,

6} , Rebecca K Pavlos _{7,

8} , Alec J Redwood ₈ , Jonathan G Peter _{9,

10} , Rannakoe Lehloenya ₉ , Simon A Mallal _{4,

5,

8} , Elizabeth J Phillips _{4,

5,

8}

Affiliation

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.
Division of Pharmacogenomics, Center for Applied Genetics and Genomic Medicine (TCAG2M), Tucson, Arizona 85721, USA.
Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA; email:
Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Subiaco, Western Australia 6008, Australia.
Institute for Immunology and Infectious Diseases, Murdoch University, Perth, Western Australia 6150, Australia.
Division of Allergy and Clinical Immunology, Department of Medicine, University of Cape Town, Cape Town 7925, South Africa.
Division of Dermatology, Department of Medicine, University of Cape Town, Cape Town 7925, South Africa.

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.

中文翻译：

免疫药物基因组学的应用：预测、预防和了解免疫介导的药物不良反应。

药物不良反应 (ADR) 是一项重大的医疗保健负担。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，造成了不成比例的高负担。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-ADR 的潜在处方筛选策略。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，专注于免疫特异性变异对药物处置和 IM-ADR 的影响。在这篇综述中，我们介绍了 HLA 与 IM-ADRs 关联的最新证据，正在进行的 IM-ADRs 生物学机制研究，以及 IM-ADRs 临床可操作生物标志物的转化，重点是 T 细胞介导的 ADRs。

更新日期：2019-01-09

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