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The study of severe cutaneous drug hypersensitivity reactions from a systems biology perspective

Perkins, James R.; Ayuso, Pedro; Cornejo-García, José A.; Ranea, Juan A.

Current Opinion in Allergy and Clinical Immunology: August 2014 - Volume 14 - Issue 4 - p 301–306
doi: 10.1097/ACI.0000000000000076
DRUG ALLERGY: Edited by Bernard Y. Thong and Miguel Blanca
Editor's Choice

Purpose of review Stevens–Johnson syndrome and toxic epidermal necrolysis are severe hypersensitivity reactions, the majority of which are drug induced. The underlying mechanisms are not fully understood. Here, we review recent findings concerning both mechanistic and genetic factors related to these diseases and propose future approaches to unravel their complexity.

Recent findings Genome-wide association study studies have identified several variants in the human leukocyte antigen region associated with these reactions. These are highly dependent on the population studied and the triggering drug. The T-cell receptor repertoire of the patient is also key. Fas–Fas ligand interactions, perforin and granulysin have also been identified as important players. Furthermore, a high-throughput gene expression study has identified a number of genes that increase in expression in patients during the acute phase of these reactions.

Summary We review recent high-throughput studies on these diseases and suggest ways in which the data can be combined and reanalyzed using integrative systems biology techniques. We also suggest future lines of research using recent technology that could shed further light on their underlying mechanisms.

aResearch Laboratory, IBIMA, Regional University Hospital of Malaga, UMA

bAllergy Unit, IBIMA, Regional University Hospital of Malaga, UMA

cDepartment of Molecular Biology and Biochemistry, Faculty of Sciences, University of Malaga

dCIBER de Enfermedades raras (CIBERER), Malaga, Spain

Correspondence to Dr José Antonio Cornejo-García, Laboratorio de Investigación, Plaza del Hospital Civil s/n, Hospital Civil, Pabellón 6, sótano. 29009 Malaga, Spain. Tel: +34 952 290 346; fax: +34 952 290 302; e-mail:

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