Project name: Homo sapiens

Description: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis(TEN) are life-threatening adverse drug reactions characterizedby massive epidermal necrosis, in which the specific dangersignals involved remain unclear. Here we show that blistercells from skin lesions of SJS-TEN primarily consist of cytotoxicT lymphocytes (CTLs) and natural killer (NK) cells, and bothblister fluids and cells were cytotoxic. Gene expression profilingidentified granulysin as the most highly expressed cytotoxicmolecule, confirmed by quantitative PCR and immunohistochemistry.Granulysin concentrations in the blister fluidswere two to four orders of magnitude higher than perforin,granzyme B or soluble Fas ligand concentrations, and depletinggranulysin reduced the cytotoxicity. Granulysin in the blisterfluids was a 15-kDa secretory form, and injection of it intomouse skin resulted in features mimicking SJS-TEN. Ourfindings demonstrate that secretory granulysin is a key moleculeresponsible for the disseminated keratinocyte death in SJS-TENand highlight a mechanism for CTL- or NK cell—mediatedcytotoxicity that does not require direct cellular contact.Overall design: Blister cells on skin lesion from 5 different patients with SJS/TEN were collected and subjected to RNA extraction without any treatment. Total RNA was isolated using the RNeasy kit (Qiagen). The 28S and 18S ribosomal RNA peak ratios were determined using microfluidics technology (Agilent). RNA was subjected to reverse transcription using the Superscript II kit (Invitrogen), and the cleaned cRNA was then hybridized to an Affymetrix human genome U133 plus 2.0 array.

Data type: Transcriptome or Gene expression

Sample scope: Multiisolate

Relevance: Medical

Last updated: 2008-11-24