Gene Expression Profiling of Skin and Blood Serum among Patients with Hidradenitis Suppurativa

Aim: To review the literature which examines the influence of gene expression in relation to patients skin, serum and clinical symptoms who have been diagnosed with hidradenitis suppurativa. Tasks: To analyze a genes variants and expression in relation to the patients skin and serum in monogenic family cases with hidradenitis suppurativa. To overlook gene expression in relation to the patients skin and serum in polygenic cases with hidradenitis suppurativa.Upon the basis of literature rewiew, to construct the methodological part of pilot study and to indicate genes could be examined, in relation to HS . Methods: The search for scientific publications was performed on the PubMed Core, Science.gov databases, using selected keywords and their combinations. Articles were selected based on the stated criteria for inclusion (articles written in 2009–2019 years., non–duplicate articles written in English, articles based on research or clinical cases) and exclusion (articles older than 2009m., duplicate articles or not written in English, review articles). The information of the publications was analysed and summarized. Results: According to clinical data, one of the major mechanisms of HS pathogenesis is impaired Notch signaling and γ–secretases consist of 4 protein subunits: one catalytic presinilin (PSEN) subunit and 3 cofactor subunits: preselin enhancer–2 (PSENEN), nicastrin (NCSTN) and (APH1) defects. PSENEN, PSEN1, NCSTN genes described in the studies result in a deficiency of Notch signal or γ–secretase, which causes Notch signal inhibition and leads to abnormal follicle keratinization, epidermal hyperplasia, cyst formation, and sebaceous gland deficiency. Polygenic changes in the CerS2 genes lead to changes in lipid composition that can clog the sweat glands. CerS2 may also be involved in the regulation of cell growth, whereas SPHK2 encodes a sphingosine kinase that accelerates the phosphorylation of sphingosine to its active form, sphingosine 1–phosphate, which in turn reduces cell homeostasis, promotes angiogenesis, and possibly carcinogenesis. The results show that keratinocytes in HS–affected skin have an inflammatory phenotype leading to an increase in inflammatory cytokines and chemokines such as IL1β, CCL5, and IP–10, leading to follicular occlusion and other cytogenesis. Studies have also shown that IL–1β can initiate a greater inflammatory response characteristic of HS by increasing the production of IL–6, IL–8, and TNF–α in keratinocyte cells. AMP plays a dual role in the pathogenesis of HS: decreased AMP activity promotes bacterial growth and biofilm formation, whereas if AMP expression is excessive, non–specific immunity is promoted and the inflammatory process is impaired. These studies also identified specifically increased skin AMP group peptides: MMP1, hBD1, hBD2, hBD3, S100A7, S100A8, S100A9 compared to psoriasis or atopic dermatitis–affected skin. Elevated interleukin levels are characteristic of HS pathogenesis: IL–8, IL–12, IL–23, IL10, IL–1b, IL–32, IL–36, IL–17. IL¬–23 is important for the development of Th17 cells that produce IL–17. The IL–12Rβ1 haplotype was also found to be directly correlated with the severity of HS. Individuals with this haplotype are 3 times more likely to have a more severe form of HS. Conclusions: 1. Studies show that only gamma secretase complex genes (NCSTN, PSEN, PSENEN) cause HS inheritance of monogenic familial cases. 2. Genes associated with antimicrobial peptides: MMP1, hBD1, hBD2, hBD3, S100A7, S100A8, S100A9, cytokines and chemokines: IL–1, IL–8, IL–12, IL–17, IL–23, IL–32, IL–36 causes the appearance of HS polygenic cases. Increased expression of interleukins IL–6, IL–8, TNF–α, IP–10 and CCL5 promotes inflammatory response, follicular occlusion, cyst formation. Increased expression of AMP peptides promotes non–specific immunity, inflammatory reactions, and decreased peptides promote bacterial growth. 3. Planning a HS genes study, it is recommended to collect skin and serum samples from patients and healthy controls. It is recommended to study genes involved in the pathogenesis of both monogenic and polygenic HS inheritance