Transcriptome patterns in hidradenitis suppurativa: support for the role of antimicrobial peptides and interferon pathways in disease pathogenesis

Abstract

Background. Hidradenitis suppurativa (HS) is a recurrent inflammatory disease of the apocrine sweat glands. Immune dysregulation probably contributes to the pathogenesis of HS. Aim. To harness mRNA expression arrays to investigate the transcriptome profile in HS compared with control skin. Methods. Illumina â HumanHT-12 v4 Expression BeadChips were used to measure mRNA expression in skin samples from HS (n = 10) and abdominoplasty (n = 11) skin specimens. Differentially expressed genes were detected by fitting genewise linear models to the normalized expression data and then modelling using the webbased software Ingenuity â Pathway Analysis. Results. The antimicrobial peptide Dermcidin and the cytokine regulator interleukin (IL)-37 were both significantly downregulated in the HS specimens (Dermcidin expression log ratio À3.93, expression P = 0.04; IL-37 expression log ratio À3.29, expression P < 0.001). Pathway analysis revealed the interferon-signalling pathway, leucocyte extravasation pathway, T helper 1 and 2 pathways and nuclear factor of activated T cells as the top-five upregulated pathways in the HS samples. Conclusion. Evaluation of transcriptome patterns in HS compared with normal skin demonstrated downregulation of the antimicrobial peptide Dermcidin and the innate immune regulator IL-37, as well as upregulation of interferon pathways and pathways of leucocyte activation.

Hair follicle stem cell replication stress drives IFI16/STING-dependent inflammation in hidradenitis suppurativa

“…Third, generation of ORSCs seems a useful and relevant model to understand the pathophysiology of HS. The transcriptomic profile of these cells revealed pathways similar to previous reports from our group and others showing enrichment for keratinocyte differentiation, epidermis development pathways (8,35), and upregulation of IFN pathways (36,37) on whole skin isolated from HS lesions. Finally, recent studies have identified a phenotypic heterogeneity in HS patients, suggesting heterogeneous pathogenic pathways.…”

Dysregulation of tryptophan catabolism at the host-skin microbiota interface in hidradenitis suppurativa

“…It is important to note that our study is the first to our knowledge to focus on a clinically homogenous group of patients with Hurley stage I. This might explain differences with previous studies, which involved patients with variable and often severe HS lesions ( 10 , 12 , 14 , 15 ). Our immune profiling of PBMCs from patients with HS highlighted higher frequencies of NK cells expressing granzyme B and perforin and producing IFN-γ upon stimulation ( Supplemental Figure 2, B–D ).…”

“…TNF-α is also frequently induced in advanced HS lesions, and the TNF-α blocker adalimumab had a positive effect on the clinical outcome of moderate-to-severe HS ( 9 ). Infiltrating myeloid cells are typically found in skin lesions, with antimicrobial peptide and IFN signatures reflecting the generation of potent innate immune responses to infection ( 6 , 10 – 15 ). An aberrant activation of neutrophils and B cells was also reported, which may jointly contribute to perpetuate lesion inflammation in patients with HS ( 12 , 13 ).…”

Hidradenitis Suppurativa: Current Understanding of Pathogenic Mechanisms and Suggestion for Treatment Algorithm

“…Intriguingly, immune responses to neutrophil and NET-related antigens have been linked to enhanced immune dysregulation and inflammation (35). In combination with the strong type I IFN signature in HS skin, these findings suggest a key involvement of the innate immune response in the pathogenesis of HS (36). As healing from the remarkable inflamation progresses, tunneling and scarring of the tissue occur (27,28,31).…”