ABSTRACT: Background Hidradenitis suppurativa (HS), psoriasis (PsO) and atopic dermatitis (AD) are inflammatory skin diseases which, despite sharing some immunological pathways, have unique disease pathogenesis and distinct pathology. For example, Th17 cells are central to PsO pathogenesis and have also been implicated in HS inflammation. AD, on the other hand, is classically referred to as a Th2-mediated disease, however incidence of AD is twice as likely in HS patients compared with healthy individuals, demonstrating an association between HS and AD. Objective To date the transcriptomics of HS, PsO and AD have not been directly compared. Therefore this study aimed to evaluate the transcriptomic differences between HS, PsO and AD lesions to identify a biological signature that defines HS inflammation. Methods Bulk RNA sequencing was performed on 19 healthy controls, 15 HS, 21 PsO and 15 AD lesional skin samples. Results Principal component analysis (PCA) identified a distinct transcriptome in HS lesions compared with healthy control skin, with increased expression of inflammatory mediators and more active inflammatory pathways including TNF, IL-17 and B cell signalling pathways. PsO lesions were defined by a strong IL-17 signature and while an IL-17 signature existed in HS lesions, HS was distinguished from PsO lesions by a unique B cell signature. When compared to AD lesions, HS lesions had a more complex inflammatory profile involving TNF, B cell and NLR signalling while AD lesions had high expression of Th2-associated genes. Weighted gene co-expression analysis suggested T cell signalling and epidermal development are important characteristics of PsO lesions while HS lesions can be defined by complement activation, B cell signalling and fibroblast-associated pathways indicating the potential for scarring in HS. Cell type deconvolution identified an enrichment of keratinocytes and T cells in PsO, Th2 cells in AD and B cells and plasma cells in HS. Finally, gene expression analysis identified increased expression of B cell, plasma cell and immunoglobulin-associated genes in HS lesions relative to healthy control skin, PsO and AD lesions. Conclusion These data suggest that HS pathogenesis is more complex than AD or PsO and highlights an important role of B and plasma cells in HS inflammation.
