Journal article
Practical Implementation of Genetics: New Concepts in Immunogenomics to Predict, Prevent, and Diagnose Drug Hypersensitivity
The Journal of Allergy and Clinical Immunology: In Practice
2022
Abstract
Delayed drug hypersensitivities are CD8+ T-cell mediated reactions associated with up to 50% mortality. Human leukocyte antigen (HLA) alleles are known to predispose disease, specific to drug, reaction, and patient ethnicity, with pre-treatment screening recommended for a handful of the strongest associations to identify and prevent drug use in high-risk patients. However, an incomplete predictive value implicates other HLA-imposed risk factors, and low carriage of many identified HLA-risk alleles combined with the high cost of sequence-based typing has limited economic viability for similar recommendation of screening across drugs and healthcare systems. To mitigate, an expanding armoury of low-cost polymerase chain reaction-based screens is being developed, and HLA-imposed risk factors are being discovered. These include (i) polymorphic variants of metabolic and endoplasmic reticulum aminopeptidase enzymes, towards multi-allelic screening with increased predictivity, (ii) regulation by immune checkpoint inhibitors, enabling de-tolerised animal models of human disease, and (iii) immunodominant T-cell receptors (TCR) on clonally-expanded CD8+ T-cells. For the latter, HLA-risk restricted TCR provides immunogenomic strategies and samples from a single patient to identify (i) novel HLA-risk associations in underserved minority populations, (ii) tissue-relevant effector biomarkers towards earlier diagnosis and treatment, and (iii) HLA-TCR-presented immunogenic structures to aid future drug development.
Details
- Title
- Practical Implementation of Genetics: New Concepts in Immunogenomics to Predict, Prevent, and Diagnose Drug Hypersensitivity
- Authors/Creators
- P. Deshpande (Author/Creator) - Murdoch UniversityY. Li (Author/Creator) - Murdoch UniversityM. Thorne (Author/Creator) - Murdoch UniversityA.M. Palubinsky (Author/Creator) - Vanderbilt University Medical CenterE.J. Phillips (Author/Creator) - Murdoch UniversityA. Gibson (Author/Creator) - Murdoch University
- Publication Details
- The Journal of Allergy and Clinical Immunology: In Practice
- Publisher
- Elsevier
- Identifiers
- 991005541408407891
- Copyright
- © 2022 Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology
- 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
- Clinical Medicine