Format

Send to

Choose Destination
J Allergy Clin Immunol. 2015 Aug;136(2):219-34; quiz 235. doi: 10.1016/j.jaci.2015.05.050.

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

Author information

1
Department of Medicine, Vanderbilt University Medical Center, Nashville, Tenn.
2
Department of Dermatology, Chang Gung Memorial Hospital, Keelung, Taiwan; Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan.
3
Program in Molecular Medicine, Institute of Pharmacology, School of Medicine, Infection and Immunity Research Center, National Yang-Ming University, Taipei, Taiwan.
4
Department of Medicine, Vanderbilt University Medical Center, Nashville, Tenn; Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Australia.
5
Department of Medicine, Vanderbilt University Medical Center, Nashville, Tenn; Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Australia. Electronic address: elizabeth.j.phillips@vanderbilt.edu.

Abstract

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.

KEYWORDS:

Abacavir; Stevens-Johnson syndrome; T-cell receptor; adverse drug reaction; allopurinol; altered peptide; carbamazepine; drug reaction with eosinophilia and systemic symptoms; hapten; heterologous immunity; human herpesvirus; human leukocyte antigen; major histocompatibility complex; p-i; pharmacogenetics; pharmacogenomics; toxic epidermal necrolysis

PMID:
26254049
PMCID:
PMC4577472
DOI:
10.1016/j.jaci.2015.05.050
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center