title: Evolving models of the immunopathogenesis of T cell-mediated drug allergy: The role of host, pathogens, and drug response.
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.
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, Tenn.
authors.forename: Katie D
authors.initials: KD
authors.lastname: White
authors.affiliation: 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.
authors.forename: Wen-Hung
authors.initials: WH
authors.lastname: Chung
authors.affiliation: Program in Molecular Medicine, Institute of Pharmacology, School of Medicine, Infection and Immunity Research Center, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Shuen-Iu
authors.initials: SI
authors.lastname: Hung
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, Tenn; Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Australia.
authors.forename: Simon
authors.initials: S
authors.lastname: Mallal
authors.affiliation: 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.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Phillips
mesh_terms: D000493:Allopurinol / Q000009:adverse effects; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D002220:Carbamazepine / Q000009:adverse effects; D015224:Dideoxynucleosides / Q000009:adverse effects; D004342:Drug Hypersensitivity / Q000209:etiology / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D005786:Gene Expression Regulation; D056426:Genetic Loci; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology*; D006801:Humans; D018448:Models, Immunological; D010597:Pharmacogenetics; D013262:Stevens-Johnson Syndrome / Q000209:etiology / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D014777:Virus Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000821:virology; D000099227:Abacavir
chemical_list: D000493:Allopurinol; D002220:Carbamazepine; D015224:Dideoxynucleosides; D006680:HLA Antigens; D000099227:Abacavir
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