• BAFF-APRIL System.
• Hidradenitis suppurativa
• IL-β; IL-18; IL-33
• ST2/IL-1R4; IHS4

Hidradenitis suppurativa is a a chronic inflammatory skin disease, characterized by clinical inflammation of the hair follicle resulting in the recurrence of abscesses, nodules, and tunnels.
The disease’s pathogenesis is multi-factorial. A role of genetics and environmental factors is recognized, but above all, being an auto-inflammatory disorder, immune system alterations are the main responsible for recurrent episodes of aberrant and spontaneous sterile inflammation. Evidence given by previous studies demonstrates that in hidradenitis suppurativa lesions an inflammatory infiltration is present, made of B/plasma cells, CD8+ cells, neutrophils, and M0 and M1 macrophages; higher than in perilesional skin or in healthy controls skin. These cells are responsible for a high secretion of inflammatory cytokines such as IL-1β, TNF-α, IL-10, and IL-17; non accompanied by a simultaneous increase in antagonists, such as IL-1Ra. Concerning neutrophils, their survival and activation is given by cytokine—granulocyte colony-stimulating factor (G-CSF), but recent studies place attention on how neutrophils can be responsible for the increase of B cells. The cytokine B-cell activating factor (BAFF) as one of the mediators highly linked to G-CSF-R has been demonstrated, and there is an upregulation of BAFF in HS lesions, while the BAFF-related mediator APRIL (aka a proliferation-inducing ligand) was unchanged. A specific role in HS pathogenesis would seem to be present, since these alterations were not seen in lesions of other diseases, such as psoriasis and atopic dermatitis.
This study has examined 24 patients affected by Hidradenitis suppurativa, followed at the Department of Dermatology of the University of Pisa, Pisa, Italy, between November 2022 and April 2023 taking a blood sample, and the main anamnestic data, such as age, BMI, present and past treatments, annual flares, disease duration, and clinical scores on diseases severity such as IHS4 (Internation Hidradenitis Suppurativa Severity Score System) and Hurley Score.
Objectives of this study are: to evaluate IL-1 family expression in HS patients in comparison with healthy donors; to study BAFF-APRIL system in HS patients in comparison with healthy donors; to correlate the cytokines expression with the main clinical and anamnestic features of the population.
On blood serum, using a R&D Systems Luminex Assays, levels of of IL-1 R2; IL-1 RA; sCD163; CCL2/MCP1; IL-17A; IL-18; IL-18 BP; IL-18 free; ST2/IL-33R; IL-33; TACI; BMCA; APRIL; BAFF/BLyS; BAFF-R were measured, and compared to the levels measured in healthy controls’ samples. These values were then correlated with the gathered anamnestic data. The most statistically significant results regard the levels of cytokines in the blood of a sub-group of patients, formed by 16 individuals who were naïve to biologic drug treatment. Biologic drug, or the respective biosimilar ones, are used in HS patients exactly because of their immuno-modulating role, carried out thanks to the binding with inflammatory molecules. Specifically, anti-TNF, anti IL-17, anti IL-12 and IL-23 are used, so they can negatively interfere with the levels of inflammatory cytokines found in blood. IL-18, free IL-18 and IL-17A levels were significantly higher in patients naive vs controls (p<0.005), while IL-1β and IL-33 levels were not different. Among soluble inhibitors, IL-1Ra, the soluble decoy receptor IL-R2 and the soluble receptor ST2/IL-1R4 were significantly increased. IL-18, free IL-18 and IL-33 levels are strongly correlated with IHS4 (p<0,0005). Also the inhibitors IL-1Ra and IL-18BP show a correlation with IHS4, even if with marginal significance (p<0,05). These data strengthen the concept of IL-1 family cytokines being connected to the development, maintenance, and severity of the disease. These discoveries open the road to the use of novel serum biomarker of active disease.