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Differential gene expression in drug hypersensitivity reactions: induction of alarmins in severe bullous diseases
Author(s) -
Bellón T.,
Álvarez L.,
Mayorga C.,
Morel E.,
Torres M.J.,
MartínDíaz M.A.,
Díaz R.,
Radial A.,
Carballo M.,
Blanca M.
Publication year - 2010
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/j.1365-2133.2009.09627.x
Subject(s) - immunology , medicine , gene expression , drug , gene , dermatology , pharmacology , biology , genetics
Summary Background Delayed hypersensitivity reactions to drugs can be life‐threatening and constitute a growing problem in clinical practice. Although drug‐specific T cells seem to be involved, the cellular and molecular bases of their aetiopathology are not fully understood. Objectives To study the molecular mechanisms underlying the pathogenesis and the clinical heterogeneity of cutaneous delayed hypersensitivity reactions to drugs. Materials and methods We characterized the gene expression profiles of peripheral blood mononuclear cells (PBMCs) isolated from patients during the acute phase of the reaction and upon resolution of clinical symptoms using a cDNA array technology. Low‐density arrays were used to confirm differential expression of selected genes during the acute disease in patients and to compare gene expression in patients and exposed control donors by quantitative real‐time polymerase chain reaction. Results Eighty‐five genes were found to be differentially expressed during the acute phase of cutaneous drug‐induced delayed hypersensitivity reactions. Furthermore, 92 genes with distinct expression patterns in severe and benign diseases during the acute phase were identified. PBMCs from patients with severe bullous diseases showed a characteristic gene expression pattern with lower expression of genes encoding T cell‐specific proteins and high expression of cell cycle‐related genes and genes coding for inflammatory‐related mediators among which several endogenous damage‐associated molecular patterns (DAMPs) or alarmins were found. Conclusions Distinct gene expression profiles in PMBCs define benign and severe clinical entities. Overexpression of endogenous DAMPs in Stevens–Johnson syndrome and toxic epidermal necrolysis suggest that drugs can trigger the alarmin system in sensitized patients leading to life‐threatening diseases.