HLA Allele-Restricted Immune-Mediated Adverse Drug Reactions: Framework for Genetic Prediction

Annu Rev Pharmacol Toxicol. 2022 Jan 6:62:509-529. doi: 10.1146/annurev-pharmtox-052120-014115. Epub 2021 Sep 13.

Abstract

Human leukocyte antigen (HLA) is a hallmark genetic marker for the prediction of certain immune-mediated adverse drug reactions (ADRs). Numerous basic and clinical research studies have provided the evidence base to push forward the clinical implementation of HLA testing for the prevention of such ADRs in susceptible patients. This review explores current translational progress in using HLA as a key susceptibility factor for immune ADRs and highlights gaps in our knowledge. Furthermore, relevant findings of HLA-mediated drug-specific T cell activation are covered, focusing on cellular approaches to link genetic associations to drug-HLA binding as a complementary approach to understand disease pathogenesis.

Keywords: HLA; drug hypersensitivity; drug safety science; pharmacogenetics; translational medicine.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alleles
  • Drug Hypersensitivity*
  • Drug-Related Side Effects and Adverse Reactions* / genetics
  • HLA Antigens / genetics
  • Humans
  • Pharmacogenetics

Substances

  • HLA Antigens