Applications of Immunopharmacogenomics: Predicting, Preventing, and Understanding Immune-Mediated Adverse Drug Reactions

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.

Keywords: Stevens-Johnson syndrome; adverse drug reaction; human leukocyte antigen; immunopharmacogenomics; pharmacogenomics; toxic epidermal necrolysis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Drug Hypersensitivity / immunology
  • Drug Hypersensitivity / prevention & control
  • Drug-Related Side Effects and Adverse Reactions / immunology*
  • Drug-Related Side Effects and Adverse Reactions / prevention & control*
  • HLA Antigens / immunology
  • Humans
  • Pharmacogenetics / methods
  • T-Lymphocytes / immunology

Substances

  • HLA Antigens