Evolving models of the immunopathogenesis of T cell-mediated drug allergy: The role of host, pathogens, and drug response.

White KD, Chung WH, Hung SI, Mallal S, Phillips EJ
J Allergy Clin Immunol. 2015 136 (2): 219-34; quiz 235

PMID: 26254049 · PMCID: PMC4577472 · DOI:10.1016/j.jaci.2015.05.050

Immune-mediated (IM) adverse drug reactions (ADRs) are an underrecognized source of preventable morbidity, mortality, and cost. Increasingly, genetic variation in the HLA loci is associated with risk of severe reactions, highlighting the importance of T-cell immune responses in the mechanisms of both B cell-mediated and primary T cell-mediated IM-ADRs. In this review we summarize the role of host genetics, microbes, and drugs in IM-ADR development; expand on the existing models of IM-ADR pathogenesis to address multiple unexplained observations; discuss the implications of this work in clinical practice today; and describe future applications for preclinical drug toxicity screening, drug design, and development.

Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

MeSH Terms (14)

Allopurinol B-Lymphocytes Carbamazepine Dideoxynucleosides Drug Hypersensitivity Gene Expression Regulation Genetic Loci HLA Antigens Humans Models, Immunological Pharmacogenetics Stevens-Johnson Syndrome T-Lymphocytes Virus Diseases

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