The autoimmune bullous disease pemphigus vulgaris (PV) is a devastating skin disease where the sole uncoupling of desmosomal cadherin desmoglein 3 (Dsg3) cell-cell adhesion is sufficient for pathogenesis. Published data from different laboratories converge to predict that the major autoimmune target Dsg3 is a significant signaling node of transcellular communication surveying biophysical, biochemical, epigenetic and genetic signaling responses. In this study, we use a multi-omics approach on human primary epidermal keratinocytes treated with experimental antibodies, AK23 (anti-Dsg3) or PX43 (anti-Dsg1/3) to elucidate the Dsg3 signalling network using systems biology. Here we describe transcriptomic profiling using RNA-seq at 5, 10 and 24 hours post antibody treatment (n=3). Although RNA-seq data for AK23 vs mIgG and PX43 vs hIgG treated groups revealed only a few statistically significant, differentially regulated genes (26 and 62, respectively, adjusted p-value ≤0.05), biostatistical analyses identified top candidate signaling pathways with known function in PV. In both treatment groups, enriched hallmark gene sets comprised MYC, E2F and TNF-α. Furthermore, reactome pathways included modulation of replication, cell cycle, WNT, Rho GTPases and apoptosis, but also new pathways pertaining to epigenetic regulation and pluripotency. In addition to abovementioned clusters, the PX43 group also showed significant enrichment of Notch, Hedgehog, mTORC1, and p53 signaling pathways, as well as keratinization. Moreover, an upregulated novel lncRNA was identified. We are currently confirming these results by duplicating the biological replicates.

LB068 - A Multi-omics approach to Pemphigus vulgaris using cultured human keratinocytes

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.