abacavir and Diabetes-Mellitus--Type-1

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.

Topics: Autoimmunity; Carbamazepine; Diabetes Mellitus, Type 1; Dideoxynucleosides; Drug Hypersensitivity; Gene Expression Regulation; HLA Antigens; Humans; Models, Molecular; Pharmacogenetics; Prognosis; Receptors, Antigen, T-Cell; Stevens-Johnson Syndrome; T-Lymphocytes; Virus Diseases