Immune Mechanisms of Drug Allergy

Katie D. White, Katherine Konvinse, Rannakoe Lehloenya, Alec Redwood, Elizabeth J. Phillips

Research output: Chapter in Book/Conference paperChapterpeer-review

Abstract

Immune-mediated adverse drug reactions (IM-ADRs) occur because of off-target interactions of medications with immune receptors and result in disproportionately high patient morbidity, mortality, and cost to drug delivery, development, and healthcare systems. IM-ADRs of greatest clinical relevance include Type I IgE-mediated anaphylaxis and delayed (Type IV) T cell-mediated pathologies across a spectrum of severity from benign exanthems to severe systemic, single-organ, and cutaneous pathologies such as drug reaction and eosinophilia and systemic symptoms, drug-induced liver disease, and Stevens-Johnson syndrome and toxic epidermal necrolysis. More recent discoveries of strong associations between human leukocyte antigen (HLA) genes and drug-specific T cell-mediated syndromes have not only provided pretreatment screening strategies for some drugs, but have also furthered our understanding of the immunopathogenesis of IM-ADR. Fundamental questions remain regarding the immunopathogenesis of T cell-mediated adverse drug reactions, including why, in most cases, only a small proportion of persons who carry a risk HLA gene will develop hypersensitivity to drug, why the clinical presentation of these syndromes varies widely, and how T cell immune responses are maintained for many years following drug exposure and resolution of clinical disease. In this chapter, we will review what is known about the immunopathogenesis of T cell-mediated adverse drug reactions with focus on drug- and syndrome-specific examples, how epidemiologic and mechanistic insights have been translated into clinical tests to prevent these syndromes, and future directions for basic science and clinical discovery in this field.

Original languageEnglish
Title of host publicationDrug Allergy Testing
PublisherElsevier
Pages27-38
Number of pages12
ISBN (Electronic)9780323497077
ISBN (Print)9780323485517
DOIs
Publication statusPublished - 2018
Externally publishedYes

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