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

Abstract

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.

IRAK4 degrader in hidradenitis suppurativa and atopic dermatitis: a phase 1 trial

“…RNA-seq analysis of skin lesions showed upregulation of multiple proinflammatory pathways in HS and AD relative to HV skin, with substantial overlap between the two diseases. This was consistent with previous publications reporting on the transcriptomic profile of AD and HS skin lesions 9 , 38 . The substantially stronger upregulation of proinflammatory gene expression that we observed with moderate to severe HS compared to AD, including genes associated with innate immunity, Th1 inflammation and humoral immune responses, is consistent with the generally greater inflammatory burden in HS associated with tissue destruction and pain and facilitated the demonstration that KT-474 treatment for 28 d could downregulate multiple different proinflammatory pathways.…”

Bulk and single-cell RNA-sequencing analyses along with abundant machine learning methods identify a novel signature in Hidradenitis Suppurativa

“…Nevertheless, a substantial portion of patients either lack identi able genetic variations or speci c mutated genes remain unidenti ed, emphasizing the imperative for continued research to elucidate the exact etiology. While numerous genes have been implicated in HS pathogenesis [7][8][9][10], limited research has speci cally addressed the aberrantly expressed gene biomarkers linked to immune in ltration in comparisons between HS and healthy control blood and skin tissues. Hence, our study aims to identify candidate hub biomarkers for HS and investigate the role of immune cell in ltration in the disease.…”

“…AKR1B10 is a nicotinamide adenine dinucleotide phosphate (reduced coenzyme II)-dependent oxidoreductase, and its biological functions include carbonyl detoxi cation, hormone metabolism, osmotic adjustment, and lipid synthesis [29]. Several studies have revealed a signi cant elevation of AKR1B family members in HS skin lesions [7,8,10]. AKR1B10 is a key enzyme involved in the expression of pro-in ammatory cytokines in SARS-CoV2 Severe Acute Respiratory Syndrome [30].…”

“…Therefore, it is crucial to identify new candidate biomarkers while nding potential therapeutic targets to enhance the prognosis of patients with HS. Previous bioinformatic studies have extensively analyzed a substantial amount of online data related to HS [7][8][9][10]. However, these projects in sample scale and scope are still somewhat limited.…”

Transcriptomic Analysis of Hidradenitis Suppurativa: A Unique Molecular Signature with Broad Immune Activation

“…In recent years, several studies have explored the alterations of the transcriptome in HS [11][12][13][14][15][16][17]. These studies have provided transcriptome-based insights into multiple genes and pathways that are dysregulated in HS including antimicrobial peptides (e.g., DEFB4A) [13,15,16], cytokines (e.g., IL17A, IL17F, IL36A, and IL36G) [12,16], T cell and B cell activation [16], and involvement of apocrine sweat glands [13,15].…”