Transcriptional profiling unravels enhanced xenobiotic metabolism in the skin of patients with atopic dermatitis but not with ichthyosis vulgaris

Previous transcriptome analyses confirmed the major role of immunological and skin barrier abnormalities in atopic dermatitis (AD). We here aimed at identifying novel pathogenic pathways involved in AD by comparing AD patients stratified for filaggrin (FLG) mutations not only to healthy donors but also to patients with ichthyosis vulgaris (IV). We applied single-molecule direct RNA-sequencing to analyze the whole transcriptome of nonlesional skin. Six hundred and one genes (478 up-regulated and 123 down-regulated by greater than 2-fold) were differentially expressed when all AD patients were compared to healthy donors. Expression of genes involved in RNA/protein synthesis, RNA splicing, and ATP synthesis was enhanced. Interestingly, genes involved in cell death, response to oxidative stress, DNA damage/repair and xenobiotic metabolism were largely enriched. Two hundred and thirty-seven genes (216 up-regulated and 21 down-regulated by greater than 2-fold) were altered in the skin of IV patients when compared to healthy donors. Remarkably, enhancement of xenobiotic metabolism was only detected in AD skin. Moreover, increased expression of genes encoding for keratinocyte cross-linking (SPRR2) and S100 proteins characterizes the skin of patients with AD flare when compared to patients without. We did not find significant differences in gene profiling between AD patients with and without FLG mutations.This work reveals new putative pathogenic pathways related to xenobiotic metabolisms involved in AD.