Dataset Information

Serum proteomic profiling uncovers dysregulated keratinization and immune-related pathways in hidradenitis suppurativa.

ABSTRACT: Hidradenitis suppurativa (HS) is an autoinflammatory keratinization disease affecting the pilosebaceous unit and hallmarked by a complex and multifactorial pathogenesis. In recent years, genetics and transcriptomics have been advancing in elucidating several crucial mechanisms underlying HS pathogenesis. Proteomic studies remain scarce, although serum proteomics holds great potential for capturing molecular signatures that reflect both cutaneous and systemic inflammation. This study presents a serum proteomic analysis of patients with moderate-to-severe HS, identifying 432 differentially expressed proteins out of 3,153 profiled. Enrichment analyses revealed dysregulated pathways related to keratinization, epidermal differentiation, and extracellular matrix remodeling, indicating impaired skin barrier function. Concurrent upregulation of immune-related pathways, including antibacterial responses and neutrophil degranulation, suggests systemic inflammation potentially linked to microbial dysbiosis. These findings support the dual role of epithelial dysfunction and autoinflammation in HS pathogenesis. Integration of proteomic data with genomic and transcriptomic findings underscores the value of multi-omics approaches in guiding targeted therapeutic development.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Cell, Blood Plasma

SUBMITTER: Michelangelo Aloisio

LAB HEAD: Blendi Ura

PROVIDER: PXD074024 | Pride | 2026-04-06

REPOSITORIES: Pride

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Serum Proteomic Profiling Uncovers Dysregulated Keratinisation and Immune-Related Pathways in Hidradenitis Suppurativa.

Moltrasio Chiara C Roncarà Sara S Ura Blendi B Nardacchione Elena Maria EM Sommella Eduardo E Moura Ronald R Derlino Federica F Marzano Angelo Valerio AV Crovella Sergio S Tricarico Paola Maura PM

Experimental dermatology 20260401 4

Hidradenitis suppurativa (HS) is an autoinflammatory keratinisation disease affecting the pilosebaceous unit and hallmarked by a complex and multifactorial pathogenesis. Although genomic and transcriptomic investigations have substantially advanced our understanding of key mechanisms underlying HS pathogenesis, proteomic studies remain limited, despite the significant potential of serum proteomics to identify molecular signatures reflecting both cutaneous and systemic inflammatory activity. This ...[more]

PMID: 41891520

Similar Datasets

Project description: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.

Project description:Objectives: To understand the crosstalk between the immune system and keratinization in psoriatic skin, using a systems biology approach based on transcriptomics, proteomics and microbiome profiling. Methods: We collected the skin tissue biopsies and swabs in both lesion and non-lesion skin of 13 patients with psoriasis (PsO), 15 patients with psoriatic arthritis (PsA), and healthy skin from 12 patients with ankylosing spondylitis (AS). We performed transcriptome sequencing and metagenomics profiling on the local skin sites to study the similarities and differences in the molecular profiles between the three conditions. To assess the systemic nature of the disease, we performed a high-throughput proteome profiling to study the profiles of proteins circulating in the serum of the same donors. Results: We found that lesion and non-lesional samples were remarkably different in terms of their transcriptome profiles. Functional annotation of differentially expressed genes (DEGs) showed a major enrichment in neutrophil activation. By using co-expression gene networks, we identified a gene module that was associated with local psoriasis severity at the site of biopsy. From this module, we extracted a “core” set of genes that were functionally involved in neutrophil activation, epidermal cell differentiation and response to bacteria. Skin microbiome analysis revealed that the abundance of Enhydrobacter, Micrococcus and Leptotrichia were significantly correlated with the “core network” of genes. We further identified 39 circulating proteins from the serum that were significantly correlated with the corresponding local skin gene expression, highlighting systemic aberrations due to skin disease. Integration of “core” genes identified from skin with circulating protein profiles revealed PI3 as a key biomarker for psoriasis. Conclusions: We identified a core network that regulates inflammation and hyper-keratinization in psoriatic skin, and is associated with local disease severity and microbiome composition. Multi-omics analysis identified PI3 as a psoriasis-specific biomarker for disease severity and potential target for treatment strategies.

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