title: Genotyping for severe drug hypersensitivity.
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.
authors.affiliation: Vanderbilt University School of Medicine, 1161-21 St Avenue South, A-2200 Medical Center North, Nashville, TN, 37232-2582, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Karlin
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Phillips
mesh_terms: D000493:Allopurinol / Q000009:adverse effects; D019980:Amoxicillin-Potassium Clavulanate Combination / Q000009:adverse effects; D002220:Carbamazepine / Q000009:adverse effects; D015224:Dideoxynucleosides / Q000009:adverse effects* / Q000737:chemistry; D004342:Drug Hypersensitivity / Q000208:ethnology / Q000235:genetics* / Q000276:immunology; D005838:Genotype; D015235:HLA-B Antigens / Q000737:chemistry / Q000235:genetics; D006801:Humans; D019829:Nevirapine / Q000009:adverse effects; D010597:Pharmacogenetics; D011487:Protein Conformation; D013262:Stevens-Johnson Syndrome / Q000235:genetics; D000099227:Abacavir
chemical_list: D000493:Allopurinol; D019980:Amoxicillin-Potassium Clavulanate Combination; D002220:Carbamazepine; D015224:Dideoxynucleosides; D015235:HLA-B Antigens; D019829:Nevirapine; D000099227:Abacavir