Journal article
HLAs: Key regulators of T-cell-mediated drug hypersensitivity
HLA, Vol.91(1), pp.3-16
2017
Abstract
Adverse drug reactions (ADR) can be broadly categorised as either on-target or off-target. On-target ADRs arise as a direct consequence of the pharmacological properties of the drug and are therefore predictable and dose-dependent. On-target ADRs comprise the majority (>80%) of ADRs, relate to the drug's interaction with its known pharmacological target and are a result of a complex interplay of genetic and ecologic factors. In contrast, off-target ADRs, including immune-mediated ADRs (IM-ADRs), are due to unintended pharmacological interactions such as inadvertent ligation of host cell receptors or non-pharmacological interactions mediated through an adaptive immune response. IM-ADRs can be classified according to the primary immune cell involved and include B-cell-mediated (Gell-Coombs type I-III reactions) and T-cell-mediated (Gell-Coombs type IV or delayed hypersensitivity) reactions. IM-ADRs mediated by T cells are associated with phenotypically distinct clinical diagnoses and can vary from a mild delayed rash to a life-threatening cutaneous, systemic or organ disease, such as Stephen Johnson syndrome/toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms and drug-induced liver disease. T-cell-mediated ADRs are strongly linked to the carriage of particular HLA risk alleles which are in the case of abacavir hypersensitivity and HLA-B*57:01 has led to translation into the clinic as a routine screening test. In this review, we will discuss the immunogenetics and pathogenesis of IM-ADRs and how HLA associations inform both pre-drug screening strategies and mechanistic understanding.
Details
- Title
- HLAs: Key regulators of T-cell-mediated drug hypersensitivity
- Authors/Creators
- A.J. Redwood (Author/Creator) - Murdoch UniversityR.K. Pavlos (Author/Creator) - Murdoch UniversityK.D. White (Author/Creator) - Vanderbilt University Medical CenterE.J. Phillips (Author/Creator) - Vanderbilt University
- Publication Details
- HLA, Vol.91(1), pp.3-16
- Publisher
- John Wiley & Sons Ltd
- Identifiers
- 991005542890607891
- Copyright
- © 2017 John Wiley & Sons A/S
- 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
- Cell Biology
- Immunology
- Pathology
- ESI research areas
- Molecular Biology & Genetics