HLA polymorphisms and their involvement in drug induced hypersensitivity reactions

Abstract

Drug induced hypersensitivity reactions (DHRs) are a result of an exaggerated immune response to a drug. DHRs commonly lead to life threatening conditions, in which several organs and tissues might be involved. Almost all drugs have been reported in DHR cases, but anti-convulsing and antibiotics are the most common drugs involved in DHRs. HLA polymorphisms are discovered to mediate DHR reactions. HLA polymorphisms are inherited from generation to generation, explaining why the prevalence of a specific DHR is higher in one population than other as in the case of HLA-1502 in the Han Chinese and carbamazepine induced DHR. The frequency of HLA-1502 alleles is higher in the Han Chinese than any other population around the world, explaining the high incidence of carbamazepine induced stevens-johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in Han Chinese patients (OR= 2500) under carbamazepine treatment. Besides HLA polymorphisms, recent findings have found that other factors might be implicated in DHR onset. In this thesis, gender, viral infections, metabolic polymorphisms/conditions and MHC polymorphisms were found to be risk factors of DHRs. The combination of one or more of these factors with HLA polymorphisms determined the frequency and severity of the DHR. Nevertheless, the interaction between each factor and the physiopathogenesis of DHR is still unknown.