title: The study of severe cutaneous drug hypersensitivity reactions from a systems biology perspective.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: James R
authors.initials: JR
authors.lastname: Perkins
authors.forename: Pedro
authors.initials: P
authors.lastname: Ayuso
authors.forename: José A
authors.initials: JA
authors.lastname: Cornejo-García
authors.forename: Juan A
authors.initials: JA
authors.lastname: Ranea
mesh_terms: D004342:Drug Hypersensitivity / Q000235:genetics / Q000276:immunology*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology*; D006801:Humans; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D013262:Stevens-Johnson Syndrome / Q000235:genetics / Q000276:immunology*; D049490:Systems Biology
chemical_list: D006680:HLA Antigens; D011948:Receptors, Antigen, T-Cell