title: New approaches for predicting T cell-mediated drug reactions: A role for inducible and potentially preventable autoimmunity.
abstract: Adverse drug reactions (ADRs) are commonplace and occur when a drug binds to its intended pharmacologic target (type A ADR) or an unintended target (type B ADR). Immunologically mediated type B ADRs, such as drug hypersensitivity syndrome, drug reaction with eosinophilia and systemic symptoms syndrome, and Stevens-Johnson syndrome/toxic epidermal necrolysis, can be severe and result in a diverse set of clinical manifestations that include fever and rash, as well as multiple organ failure (liver, kidney, lungs, and/or heart) in the case of drug hypersensitivity syndrome. There is increasing evidence that specific HLA alleles influence the risk of drug reactions. Several features of T cell-mediated ADRs are strikingly similar to those displayed by patients with autoimmune diseases like type I diabetes, such as strong HLA association, organ-specific adaptive immune responses, viral involvement, and activation of innate immunity. There is a need to better predict patient populations at risk for immunologically mediated type B ADRs. Because methods to predict type 1 diabetes by using genetic and immunologic biomarkers have been developed to a high level of accuracy (predicting 100% of subjects likely to progress), new research strategies based on these methods might also improve the ability to predict drug hypersensitivity.
authors.affiliation: Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, Colo.
authors.forename: Aaron W
authors.initials: AW
authors.lastname: Michels
authors.affiliation: Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, Fla. Electronic address: ostroda@pathology.ufl.edu.
authors.forename: David A
authors.initials: DA
authors.lastname: Ostrov
mesh_terms: D015551:Autoimmunity / Q000187:drug effects*; D002220:Carbamazepine / Q000009:adverse effects; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis / Q000235:genetics / Q000276:immunology; D015224:Dideoxynucleosides / Q000009:adverse effects; D004342:Drug Hypersensitivity / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008958:Models, Molecular; D010597:Pharmacogenetics; D011379:Prognosis; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D013262:Stevens-Johnson Syndrome / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D014777:Virus Diseases / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000821:virology; D000099227:Abacavir
chemical_list: D002220:Carbamazepine; D015224:Dideoxynucleosides; D006680:HLA Antigens; D011948:Receptors, Antigen, T-Cell; D000099227:Abacavir
keywords: T cell; adverse drug reaction; autoimmunity