A Hidradenitis Suppurativa molecular disease signature derived from patient samples by high-throughput RNA sequencing and re-analysis of previously reported transcriptomic data sets

Hidradenitis suppurativa (HS) is a common, debilitating inflammatory skin disease linked to immune dysregulation and abnormalities in follicular structure and function. Several studies have characterized the transcriptomic profile of affected and unaffected skin in small populations. In this study of 20 patients, RNA from lesional and matching non-lesional skin biopsies in 20 subjects were used to identify an expression-based HS disease signature. This was followed by differential expression and pathway enrichment analyses, as well as jointly reanalyzing our findings with previously published transcriptomic profiles. We establish an RNA-Seq based HS expression disease signature that is mostly consistent with previous reports. Bulk-RNA profiles from 104 subjects in 7 previously reported data sets identified a disease signature of 118 differentially regulated genes compared to three control data sets from non-lesional skin. We confirmed previously reported expression profiles and further characterized dysregulation in complement activation and host response to bacteria in disease pathogenesis. Changes in the transcriptome of lesional skin in this cohort of HS patients is consistent with smaller previously reported populations. The findings further support the significance of immune dysregulation, in particular with regard to bacterial response mechanisms. Joint analysis of this and previously reported cohorts indicate a remarkably consistent expression profile.