Abstract
Hidradenitis suppurativa (HS) is a chronic skin disease of the pilo-sebaceous apocrine unit characterized by significant inflammation and an impaired quality of life. The pathogenesis of HS remains unclear. To determine the HS skin and blood transcriptomes and HS blood proteome, patient data from previously published studies were analysed and integrated from a cohort of patients with moderate to severe HS (n = 17) compared to healthy volunteers (n = 10). The analysis utilized empirical Bayes methods to determine differentially expressed genes (DEGs) (fold change (FCH) >2.0 and false discovery rate (FDR) <0.05), and differentially expressed proteins (DEPs) (FCH>1.5, FDR<0.05). In the HS skin transcriptome (lesional skin compared to non-lesional skin), there was an abundance of immunoglobulins, antimicrobial peptides, and an interferon signature. Gene-sets related to Notch signalling and Interferon pathways were differentially activated in lesional compared to non-lesional skin. CIBERSORT analysis of the HS skin transcriptome revealed a significantly increased proportion of plasma cells in lesional skin. In the HS skin and blood transcriptomes and HS blood proteome, gene-sets related to the complement system changed significantly (FDR<0.05), with dysregulation of complement-specific DEGs and DEPs. These data point towards an exaggerated immune response in lesional skin that may be responding to commensal cutaneous bacterial presence and raise the possibility that this may be an important driver of HS disease progression.
Highlights
The pathogenesis of the debilitating chronic skin disease hidradenitis suppurativa (HS) is still not well understood
HS skin transcriptome was dominated by immunoglobulins, antimicrobial peptides (AMPs), an interferon signature, and plasma cells
Nine of the top 50 upregulated differentially expressed genes (DEGs) in HS were genes known to be upregulated in psoriasis (PS), including AMPs S100A7, A9, DEFB4, as well as SERPINB3 AND B4 [13]
Summary
The pathogenesis of the debilitating chronic skin disease hidradenitis suppurativa (HS) is still not well understood. A consistent observation is obstruction at the follicular infundibulum in apocrine gland bearing skin, and it seems possible that there are a number of initiating factors that could predispose to this development, reviewed in Hoffman et al [1]. A proposed pathogenic pathway involves apocrine secretions accumulating in the hair follicle, which eventually ruptures onto the surface of the skin or into the dermis. As this process is repeated, the inflammatory cascade leads to recurrent abscesses, suppurative dermal tunnels, and fibrosis. Many of the discoveries regarding HS to date have not been distinctive of HS, but reflect general cutaneous inflammatory responses to insults [2], along with a lack of resolution of the inflammatory process [3]
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