Personalized medicine for HLA-associated drug-hypersensitivity reactions

Abstract

Multiple genetic and nongenetic factors can modify the action of a drug, resulting in varied responses to a particular drug across different individuals. Personalized medicine incorporates the comprehensive knowledge of these factors to facilitate the selection of optimal therapy, reduce adverse drug reactions, increase patient compliance and increase the efficiency of therapy. Pharmacogenomics, which integrates the knowledge of an individual’s genetic make-up for diagnostic decisions or therapeutic interventions is closely linked to personalized medicine, and is being increasingly used to prevent adverse drug reactions. There are various reports on genetic associations between particular HLA allotypes and drug hypersensitivities and the strongest associations reported thus far, are with the reverse transcriptase inhibitor, abacavir and HLA-B*5701, the gout prophylactic allopurinol and HLA-B*5801 and the antiepileptic carbamazepine and B*1502, providing a defined disease trigger and suggesting a general mechanism for these associations. Recognizing the strong HLA association, the US FDA has recommended genetic testing before starting abacavir and carbamazepine therapies. To incorporate HLA testing for other drug hypersensitivities and life-threatening reactions it is essential first to establish clear HLA associations, and second, to understand the immune-mechanism by which these drugs induce HLA-linked hypersensitivity. The latter will provide insight into the pathologic mechanisms of drug allergy allowing rational immunotherapy for these life-threatening reactions and the development of alternative drug therapies for hypersensitive patients.