Tiffany K Roberts
University of Louisville, USA
Title: To live and die by HLA: drug reactions and hypersensitivities
Biography
Biography: Tiffany K Roberts
Abstract
Statement of the Problem: Adverse drug reactions (ADRs) remain a common and major problem in healthcare. Severe cutaneous adverse drug reactions (SCARs), such as Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) with mortality rate ranges from 10% to more than 30%, can be life threatening. ADRs induced by several drugs have been shown to have significant associations with specific alleles of human leukocyte antigen (HLA) genes.
Methodology & Theoretical Orientation: Drugs or reactive metabolites are considered as foreign antigens that bind to T cell receptors (TCR) and further activate immune response. Several hypotheses have been proposed to explain how the immune system is activated in a HLA molecule-dependent manner.
Findings: Hypersensitivity to abacavir, a drug used for treating of human immunodeficiency virus (HIV) infection, has been proposed to be associated with allele 57:01 of HLA-B gene (terms HLA-B∗57:01). The incidences of abacavir hypersensitivity are much higher in Caucasians compared to other populations due to various allele frequencies in different ethnic populations. The antithyroid drug- (ATDs-) induced agranulocytosis are strongly associated with two alleles: HLA-B∗38:02 and HLA-DRB1∗08:03. In addition, HLA-B∗15:02 allele was reported to be related to carbamazepine-induced SJS/TEN, and HLA-B∗57:01 in abacavir hypersensitivity and flucloxacillin induced drug-induced liver injury (DILI).
Conclusion & Significance: This talk will summarize the alleles of HLA genes which have been proposed to have association with ADRs caused by different drugs.