ANAPHYLAXIS AND DRUG ALLERGY (DA KHAN AND M CASTELLS, SECTION EDITORS)

Current Allergy and Asthma Reports

, 14:418

First online:

Genotyping for Severe Drug Hypersensitivity

  • Eric KarlinAffiliated withVanderbilt University School of Medicine
  • , Elizabeth PhillipsAffiliated withVanderbilt University School of MedicineInstitute for Immunology and Infectious Diseases, Murdoch University Email author 

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Abstract

Over the past decade, there have been significant advances in our understanding of the immunopathogenesis and pharmacogenomics of severe immunologically-mediated adverse drug reactions. Such T-cell-mediated adverse drug reactions such as Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), drug-induced liver disease (DILI) and other drug hypersensitivity syndromes have more recently been shown to be mediated through interactions with various class I and II HLA alleles. Key examples have included the associations of HLA-B*15:02 and carbamazepine induced SJS/TEN in Southeast Asian populations and HLA-B*57:01 and abacavir hypersensitivity. HLA-B*57:01 screening to prevent abacavir hypersensitivity exemplifies a successful translational roadmap from pharmacogenomic discovery through to widespread clinical implementation. Ultimately, our increased understanding of the interaction between drugs and the MHC could be used to inform drug design and drive pre-clinical toxicity programs to improve drug safety.

Keywords

Genotyping Altered peptide repertoire DILI DRESS Human leukocyte antigen Drug hypersensitivity Major histocompatibility complex Pharmacogenetics Pharmacogenomics Stevens-Johnson syndrome Toxic epidermal necrolysis Translation SCAR