Document Detail

Differential gene expression in drug hypersensitivity reactions: induction of alarmins in severe bullous diseases.
MedLine Citation:
PMID:  20030638     Owner:  NLM     Status:  MEDLINE    
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.
T Bell?n; L Alvarez; C Mayorga; E Morel; M J Torres; M A Mart?n-D?az; R D?az; A Radial; M Carballo; M Blanca
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-02-25
Journal Detail:
Title:  The British journal of dermatology     Volume:  162     ISSN:  1365-2133     ISO Abbreviation:  Br. J. Dermatol.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-04-28     Completed Date:  2010-06-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0004041     Medline TA:  Br J Dermatol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1014-22     Citation Subset:  IM    
Research Unit, Hospital La Paz-FIBHULP, P masculine Castellana 261, 28046 Madrid, Spain.
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MeSH Terms
Acute Disease
Aged, 80 and over
Drug Eruptions / genetics,  immunology,  metabolism*
Epidermal Necrolysis, Toxic / genetics,  immunology,  metabolism
Gene Expression Profiling / methods
Genes, cdc
Immunity, Innate
Inflammation Mediators / metabolism
Leukocytes, Mononuclear / metabolism
Middle Aged
Oligonucleotide Array Sequence Analysis / methods
RNA, Messenger / genetics
Reverse Transcriptase Polymerase Chain Reaction / methods
Skin Diseases, Vesiculobullous / chemically induced*,  genetics,  immunology,  metabolism
Stevens-Johnson Syndrome / chemically induced,  genetics,  immunology,  metabolism
T-Lymphocytes / metabolism
Reg. No./Substance:
0/Inflammation Mediators; 0/RNA, Messenger

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