Toxicology Research REVIEW Cite this: Toxicol. Res., 2015, 4, 777 Received 17th December 2014, Accepted 4th February 2015 DOI: 10.1039/c4tx00238e www.rsc.org/toxicology Towards the development of mechanism-based biomarkers to diagnose drug hypersensitivity N. Duran-Figueroa, a J. A. Badillo-Corona, a D. J. Naisbitt b and J. L. Castrejon-Flores* a Drug hypersensitivity reactions or drug allergy is a form of serious adverse drug reaction with an immuno- logical aetiology to otherwise safe and effective therapeutic agents. The use of certain classes of drugs (e. g., antibiotics, anti-convulsants and anti-retrovirals) is associated with a particular high frequency of reac- tions. The skin is the organ most commonly targeted in drug hypersensitivity reactions; however, other organs can be damaged in isolation or as part of a generalized hypersensitivity syndrome. Diverse epide- miological studies have been performed in order to estimate the incidence of drug hypersensitivity, but due to the heterogeneous presentation, different immunological mechanisms involved and the lack of simple and cost-effective in vitro tests to confirm a clinical diagnosis, the real incidence remains elusive. Furthermore, lack of knowledge relating to the way in which drugs interact with immune cells has hin- dered attempts to develop such tests. Nonetheless, during the last thirty years several groups have demonstrated that drug-responsive lymphocytes playa key role in the pathogenesis of most forms of this iatrogenic disease. This present review focus on (1) the cellular mechanism involved in drug hypersensitiv- ity and (2) the biomarkers used to diagnose drug hypersensitivity. In addition, using our increasing knowl- edge of post-transcriptional immune regulators, such as microRNAs, we explored the possibility of identifying novel drug hypersensitivity biomarkers and their possible application in assays to diagnose drug hypersensitivity reactions in susceptible patients. 1. Adverse drug reactions Drugs elicit their therapeutical action by mimicking or block- ing the action of endogenous molecules on receptors found in target tissues and cells. However, several factors from a diverse nature such as an exaggerated pharmacology as a result of Noe Valentin Duran Figueroa Noe Valentin Duran Figueroa received a PhD degree from CIN- VESTAV-Mexico in Plant Mole- cular Biology with a thesis focused on studying the function of microRNAs and Argonaute proteins in reproductive develop- ment. Since 2011, he is principal investigator at Instituto Politec- nico Nacional in Mexico City and founded the Laboratory Molecular Biology of RNA. His research focuses on the mole- cular function of microRNAs in cellular communication and in the use of microRNAs as Bio- markers for diagnostic and treatment. Jesus Agustin Badillo-Corona Jesus Agustin Badillo-Corona is a reader of Molecular Biology at Instituto Politecnico Nacional in Mexico City. He received a PhD degree from the University of Cambridge in 2007 with a thesis focusing in the development of plant-based vaccines against HIV and diabetes. Since 2008, Dr. Badillo-Corona is principal investigator and leader of the Laboratory of Biotechnology where part of his research focuses on evaluating the safety and effect of plant proteins in animal cells in vitro. a Instituto Politécnico Nacional, Unidad Profesional Interdisciplinaria de Biotecnología, Mexico City, Mexico. E-mail: jlcastrejonf@gmail.com b MRC Centre for Drug Safety Science, Department of Pharmacology, University of Liverpool, Liverpool, Merseyside, UK This journal is © The Royal Society of Chemistry 2015 Toxicol. Res. , 2015, 4, 777–795 | 777 Downloaded from https://academic.oup.com/toxres/article/4/4/777/5573536 by guest on 21 January 2023