Contributions of pharmacogenetics and transcriptomics to the understanding of the hypersensitivity drug reactions

Hypersensitivity drug reactions (HDRs) represent a large and important health problem, affecting many patients and leading to a variety of clinical entities, some of which can be life-threatening. The culprit drugs include commonly used medications including antibiotics and NSAIDs. Nontherapeutical agents, such as contrast media, are also involved. Because the pathophysiological mechanisms are not well known and the current diagnostic procedures are somewhat insufficient, new approaches are needed for understanding the complexity of HDRs. Histochemical and molecular biology studies have enabled us to classify these reactions more precisely. Pharmacogenetics has led to the identification of several genes, involved mainly in T-cell-dependent responses, with a number of markers being replicated in different studies. These markers are now being considered as potential targets for reducing the number of HDRs. Transcriptomic approaches have also been used to investigate HDRs by identifying genes that show different patterns of expression in a number of clinical entities. This information can be of value for further elucidation of the mechanisms involved. Although first studies were performed using RT-PCR analysis to monitor the acute phase of the reaction, nowadays high-density expression platforms represent a more integrative way for providing a complete view of gene expression. By combining a detailed and precise clinical description with information obtained by these approaches, we will obtain a better understanding and management of patients with HDRs.