069 Transcriptome analysis of pyoderma gangrenosum reveals an activation of innate immunity, cell cycle and regulated cell death pathways

Abstract

Pyoderma gangrenosum (PG) is an autoinflammatory disease leading to extremely painful and highly inflamed ulcers of the skin. Immune mechanisms driving chronic inflammation as well as optimal treatment strategies are still elusive. Here we performed RNA-sequencing analysis of 7 PG skin biopsies and 2 autologous non-involved skin samples. Gene expression was compared between the group of lesional versus non-lesional skin samples. Pathway analysis was performed using KEGG, Reactome, Biocarta and PID databases. For enrichment, all genes with a false discovery rate less than 0.1 were considered. We observed a significant activation of toll-like-receptor signalling and gamma-delta T cells, angiogenesis, and the integrin pathway in PG compared to non-involved skin. Induced modules network analysis of the 500 most significantly differentially expression genes revealed that STAT3 as well as genes regulating cell cycle (CCND1, CDKN1A) and cell death (BCL2) are hub genes in the molecular signature of PG. Hence, transcriptome of PG is composed of an upregulation of innate immunity, cell cycle and regulated cell death. These data might be useful to define future treatment approaches of PG.