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M. Ueta, C. Sotozono, T. Inatomi, J. Hamuro, S. Kinoshita; Gene Expression Analysis of Monocytes Derived From the Patients of Stevens-johnson Syndrome With Ocular Complications. Invest. Ophthalmol. Vis. Sci. 2007;48(13):386.
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Stevens-Johnson syndrome (SJS) / toxic epidermal necrolysis (TEN) is an acute inflammatory vesiculobullous reaction of the skin and mucous membranes. It is commonly associated with infectious agents or inciting drugs. The pathophysiological mechanisms underlying the onset of SJS/TEN have not been fully established. Given the association between SJS and infections, and the persistence of ocular surface inflammation and opportunistic infection of ocular surfaces by bacteria, we considered the possibility that there is an association between the pathophysiology of SJS/TEN and a disordered innate immune response. Therefore, we performed gene expression analysis of monocytes using a GeneChip to examine the disordered innate immune response in SJS/TEN with ocular complications (SJS/TENoc).
We enrolled 7 Japanese patients with SJS/TENoc in the chronic phase and 6 healthy controls. Human monocytes, isolated with MACS using anti-human CD14 mAbs coating microbeads, were, or were not, cultured for 1 hr in medium or activated with 100 ng/ml LPS. Gene expression profiles were investigated using the GeneChip of human Genome U133 Plus2.0 (Affymetrix). Down- and up-regulated genes were analyzed by Ingenuity Pathways Analysis. The results were confirmed by quantitative RT-PCR assay.
After 1-hr culture, but not non-culture or 1-hr culture with LPS, the expression of IL-1α and IΚBζ mRNA was reduced in peripheral monocytes from SJS/TENoc patients as compared to that from healthy controls. The gene expression changes of innate immune response-related genes were confirmed in 1-hr cultures of monocytes.
Our findings suggest that there is the possibility that the pathophysiology of SJS is associated with a disordered innate immune response.
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