Evaluation of pruritus biomarkers expression in chronic spontaneous urticaria

Chronic urticaria (CU) is a skin disease characterized by recurrent episodes of urticaria and/or angioedema, persisting for more than six weeks. Chronic urticaria is classified as chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIndU). Histamine, released by mast cells and basophils, is the central mediator in the development of signs and symptoms, especially pruritus. IL-31 activates pruritus via IL-31RA. Th2 cytokines also contributes to the inflammatory environment, releasing further IL-31. We aimed to investigate the quantification of mast cells, expression of pro-inflammatory cytokines in skin samples from individuals with CU and cell activation by the basophil activation test. Thirteen patients with CSU, 11 patients with CIndU and 10 healthy controls (HC) were enrolled in the study. We performed histologic quantification of the mast cells, metachromatic stained with toluidine blue, in CSU and CIndU lesional samples; IL-31, IL-31RA, IL-4 and IFN-γ expression by immunohistochemistry; and basophil activation test (BAT) by flow cytometry. The main findings were increased mast cell quantification in CSU; increased epidermal and dermal expression of IL-31 in CSU lesional samples and increased dermal expression in CIndU samples; augmented IL-31RA expression at epidermis and dermis of CSU group; augmented expression IL-4 at epidermis of CSU patients. We also found enhanced BAT positivity in CSU, reinforcing the autoimmune profile of our CSU patients. The analysis of the proinflammatory cytokines related to pruritus, showed increased expression of the evaluated components. These remarkable findings in CSU emphasize their relevance as potential disease biomarkers and targets for immunomodulatory interventions.