Transcriptomic analysis of hidradenitis suppurativa skin suggests roles for multiple inflammatory pathways in disease pathogenesis.

Abstract

Hidradenitis suppurativa (HS) is a chronic inflammatory disease with limited treatment options; therefore, the current study investigated the downstream signaling pathways that are differentially expressed in HS subjects and may drive disease pathogenesis. The expression of 144 genes was evaluated in the skin of 16 healthy subjects and 34 subjects with mild to severe HS using QuantiGene Plex assay. One hundred and twenty-nine genes were significantly elevated in lesional HS skin as compared to the skin of healthy controls including pro-inflammatory cytokines (IL-1α, IL-6, TNF-α), IL-17-associated cytokines (IL-17A, IL-17F, IL-23A), the IL-10 family of cytokines (IL-10, IL-19, IL-20, IL-22, IL-24), and IFN family members (IFNA1, IFNB1, IFNG, IL-12B). This corresponded with increased expression of tyrosine kinases (JAK1, JAK3, BTK, SYK) and their downstream signaling partners (STAT1, STAT2, STAT3, STAT5A, STAT5B, STAT6). These data illustrate the diverse immune activation in lesional HS skin and suggest that deeper interrogation of the disease heterogeneity may reveal unique opportunities for targeted therapies in designated subpopulations.