Apocrine glands are bystanders in hidradenitis suppurativa and their involvement is gender specific

Abstract

BackgroundApocrine glands have been long considered as the initial targeted skin compartment in hidradenitis suppurativa/acne inversa (HS).ObjectiveDetection of apocrine gland involvement in HS.MethodsApocrine glands were isolated from skin biopsies of involved and uninvolved skin of HS patients (n = 16, females : males 1 : 1) by laser capture microscopy and studied by whole transcriptome profiling. Dysregulated genes were detected by comparing lesional and non‐lesional skin obtained from female and male HS patients using the Agilent array platform.ResultsSULF1 was the only gene, whose expression levels were found upregulated in apocrine glands of HS lesions of the entire group. Further dysregulated genes associated with vascular functions (FGF1, IL17D and S100A9) were detected. Genes, which are characteristic for glandular epithelia, confirmed the glandular origin of the studied tissue. The gene upregulation profile of female apocrine glands included several genes (MRO, DYRK3, SDK2, GLB1L, CATSPERB and PRPS2), which are specifically transcribed during testis differentiation and/or regulated by androgens. Genes related to lipid metabolism (AGPAT3, GAL, ELOVL3, THRSP, DGAT2L3, OLAH, THRSP, FADS1, NR2F2, FADS2, PTGDS and HAO2) were mostly downregulated in the apocrine glands of male patients. The levels of RECK and PCSK5, which are upstream genes of metalloproteinase‐9 and ‐1, and of S100A9, which encodes calgranulin B, were commonly increased in the apocrine glands of female and male patients, respectively, and in our previous whole skin study.ConclusionOur findings indicate that apocrine glands are bystanders in HS. Inflammatory signalling is not prominent but a gender‐specific response was detected, which is mostly associated with androgen‐responsive genes in females and alterations of lipid metabolism in males.

Hidradenitis suppurativa is an autoinflammatory keratinization disease: A review of the clinical, histologic, and molecular evidence

“…[78][79][80] This is further perpetuated through leucocytekeratinocyte interactions, [78][79][80] further amplifying antimicrobial peptide and chemokine production (including CXCL1 and CXCL8), 81 leading to further inflammatory cell recruitment adjacent to IL-17eactivated epidermal keratinocytes (Fig 3). Such inflammatory cell localization has been observed surrounding intrafollicular and interfollicular sites adjacent to epidermal keratinocytes in early histologic specimens of hidradenitis suppurativa, [9][10][11]64 with evidence of early psoriasiform hyperplasia suggestive of IL-17einduced epidermal changes.…”

What causes hidradenitis suppurativa ?—15 years after

“…In contrast, histopathologic and molecular studies indicate significant involvement of the hair follicle with secondary apocrine gland injury. [156][157][158][159] There are a number of changes in the hair follicle including an occluding spongiform inflammation in the infundibulum with predominantly T cells and infundibular disintegration in early lesions. 157,160 Hair follicle keratinocytes also produce more proinflammatory cytokines and have an altered pattern of antimicrobial peptide production.…”

The most recent advances in understanding and managing hidradenitis suppurativa

“…Their findings indicated that in contrast to the entire lesional skin in HS patients, an inflammatory signal was not prominent in the apocrine glands. The key dysregulated pathway in female lesional skin was the androgen signaling pathway and in males was the lipid metabolism pathway, reflected in gender-specific transcriptomes 13 .…”