Journal article
Role of pharmacogenomics in T-cell hypersensitivity drug reactions
Current Opinion in Allergy & Clinical Immunology, Vol.21(4), pp.327-334
2021
Abstract
Purpose of review
An update of the pharmacogenetic risk factors associated with T-cell-mediated delayed hypersensitivity reactions.
Recent findings
Recent HLA associations relevant to our understanding of immunopathogenesis and clinical practice include HLA-B∗13:01 with co-trimoxazole-induced SCAR, and HLA-A∗32:01 with vancomycin-DRESS, for which an extended HLA class II haplotype is implicated in glycopeptide antibiotic cross-reactivity. Hypoactive variants of ERAP1, an enzyme-trimming peptide prior to HLA loading, are now associated with protection from abacavir-hypersensitivity in HLA-B∗57:01+ patients, and single-cell sequencing has defined the skin-restricted expansion of a single, public and drug-reactive dominant TCR across patients with HLA-B∗15:02-restricted carbamazepine-induced SJS/TEN. More recent strategies for the use of HLA and other risk factors may include risk-stratification, early diagnosis, and diagnosis in addition to screening.
Summary
HLA is necessary but insufficient as a risk factor for the development of most T-cell-mediated reactions. Newly emerged genetic and ecological risk factors, combined with HLA-restricted response, align with underlying immunopathogenesis and drive towards enhanced strategies to improve positive-predictive and negative-predictive values. With large population-matched cohorts, genetic studies typically focus on populations that have been readily accessible to research studies, but it is now imperative to address similar risk in globally relevant and understudied populations.
Details
- Title
- Role of pharmacogenomics in T-cell hypersensitivity drug reactions
- Authors/Creators
- R.J. Hertzman (Author/Creator)P. Deshpande (Author/Creator)A. Gibson (Author/Creator)E.J. Phillips (Author/Creator)
- Publication Details
- Current Opinion in Allergy & Clinical Immunology, Vol.21(4), pp.327-334
- Publisher
- Wolters Kluwer
- Identifiers
- 991005540774407891
- Copyright
- © 2021 Wolters Kluwer Health
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.265 Dermatology - Skin Allergies
- 1.265.1140 Drug Hypersensitivity
- Web Of Science research areas
- Allergy
- Immunology
- ESI research areas
- Immunology