Background The large unmet need of hidradenitis suppurativa/acne inversa (HS) therapy requires the elucidation of disease‐driving mechanisms and tissue targeting. Objective Robust characterization of the underlying HS mechanisms and detection of the involved skin compartments. Methods Hidradenitis suppurativa/acne inversa molecular taxonomy and key signalling pathways were studied by whole transcriptome profiling. Dysregulated genes were detected by comparing lesional and non‐lesional skin obtained from female HS patients and matched healthy controls using the Agilent array platform. The differential gene expression was confirmed by quantitative real‐time PCR and targeted protein characterization via immunohistochemistry in another set of female patients. HS‐involved skin compartments were also recognized by immunohistochemistry. Results Alterations to key regulatory pathways involving glucocorticoid receptor, atherosclerosis, HIF1α and IL17A signalling as well as inhibition of matrix metalloproteases were detected. From a functional standpoint, cellular assembly, maintenance and movement, haematological system development and function, immune cell trafficking and antimicrobial response were key processes probably being affected in HS. Sixteen genes were found to characterize HS from a molecular standpoint (DEFB4, MMP1, GJB2, PI3, KRT16, MMP9, SERPINB4, SERPINB3, SPRR3, S100A8, S100A9, S100A12, S100A7A (15), KRT6A, TCN1, TMPRSS11D). Among the proteins strongly expressed in HS, calgranulin‐A, calgranulin‐B and serpin‐B4 were detected in the hair root sheath, koebnerisin and connexin‐32 in stratum granulosum, transcobalamin‐1 in stratum spinosum/hair root sheath, small prolin‐rich protein‐3 in apocrine sweat gland ducts/sebaceous glands‐ducts and matrix metallopeptidase‐9 in resident monocytes. Conclusion Our findings highlight a panel of immune‐related drivers in HS, which influence innate immunity and cell differentiation in follicular and epidermal keratinocytes as well as skin glands.

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.

Dynamical decoupling sequences detect spin system and solvent-induced decoherence contributions for nitroxides, trityl radicals and gadolinium complexes in glassy water–glycerol.

Chronic inflammation and dysregulated epithelial differentiation, especially of hair follicle keratinocytes, have been suggested as the major pathogenetic pathways of hidradenitis suppurativa/acne inversa (HS). On the other hand, obesity and metabolic syndrome have additionally been considered as an important risk factor. With adalimumab, a drug has already been approved and numerous other compounds are in advanced-stage clinical studies. A systematic review was conducted to detect and corroborate HS pathogenetic mechanisms at the molecular level and identify HS molecular markers. The obtained data were used to confirm studied and off-label administered drugs and to identify additional compounds for drug repurposing. A robust, strongly associated group of HS biomarkers was detected. The triad of HS pathogenesis, namely upregulated inflammation, altered epithelial differentiation and dysregulated metabolism/hormone signaling was confirmed, the molecular association of HS with certain comorbid disorders, such as inflammatory bowel disease, arthritis, type I diabetes mellitus and lipids/atherosclerosis/adipogenesis was verified and common biomarkers were identified. The molecular suitability of compounds in clinical studies was confirmed and 31 potential HS repurposing drugs, among them 10 drugs already launched for other disorders, were detected. This systematic review provides evidence for the importance of molecular studies to advance the knowledge regarding pathogenesis, future treatment and biomarker-supported clinical course follow-up in HS.