Work

New Strategies to Predict and Prevent Serious Immunologically Mediated Adverse Drug Reactions.

Year: 2018

Type: article

Abstract: Preventive efforts for serious immunologically mediated adverse drug reactions (IM-ADRs) have been fueled by discovery of strong class I human leukocyte antigen (HLA) associations; however, the low positive predictive value of HLA for IM-ADRs has limited translation. Studies were undertaken to explain why most patients carrying an HLA risk allele do not develop IM-ADR on exposure to the risk drug. Tissue-specific approaches defined the T-cell receptor (TCR) repertoire and phenotype of the pathogenic T cells found in the skin and blister fluid of IM-ADRs. Dominant CD8+ T cell clonotypes representing >50% of total TCRαβ sequences among CD8+ CD137+ T cells were identified in tissue to identify the pathogenic activated T cells. Identification of the specific molecular and cellular signatures of the antigen-driven pathogenic T cells will facilitate more specific mechanisms to determine the small percentage of individuals carrying an HLA risk allele who are likely to develop an IM-ADR before drug exposure.

Source: Europe PMC (PubMed Central)

Author: Elizabeth J Phillips

Language: English

Topic: Drug-Induced Adverse Reactions

Subfield: Pharmacology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases

Awards: Stevens-Johnson Syndrome/Toxic Epidural Necrolysis 2017: Building Multidisciplinary Networks to Drive Science and Translation, Improving Prediction of Drug Action, The Structural and Functional Basis of HLA-associated Drug Hypersensitivity, Tennessee Center for AIDS Research (TN-CFAR)

OpenAlex ID: W2990942850

FWCI: 0.806

Cites: 15

Cited by: 7

Related to: 10