期刊
CURRENT ALLERGY AND ASTHMA REPORTS
卷 14, 期 3, 页码 -出版社
CURRENT MEDICINE GROUP
DOI: 10.1007/s11882-013-0418-0
关键词
Genotyping; Altered peptide repertoire; DILI; DRESS; Human leukocyte antigen; Drug hypersensitivity; Major histocompatibility complex; Pharmacogenetics; Pharmacogenomics; Stevens-Johnson syndrome; Toxic epidermal necrolysis; Translation; SCAR
资金
- UpToDate
- Merck Pty Ltd.
- ViiV Australia
- Gilead Australia
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: 02and 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.
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