Gasdermin-Mediated Pyroptosis in Hidradenitis Suppurativa: Molecular Insights and Therapeutic Implications.

Abstract

Hidradenitis suppurativa (HS) is a debilitating inflammatory skin condition with unclear underlying mechanisms. Recent studies suggest pyroptosis, a highly inflammatory form of programmed cell death, could significantly contribute to the disease process. This study aimed to investigate the roles of gasdermin D (GSDMD) and gasdermin E (GSDME), two key mediators of pyroptosis, in HS pathogenesis. Serum and skin samples from HS patients and healthy individuals were analyzed. Serum gasdermin D levels were significantly elevated in HS patients, although gasdermin E showed no significant difference compared to controls. Skin tissue analysis revealed increased expression of both GSDMD and GSDME in inflamed HS lesions compared to unaffected skin from the same patients and healthy control skin. However, these molecules did not correlate directly with disease severity. Interestingly, systemic metabolic markers showed some associations with gasdermin expression, suggesting potential connections between systemic health and inflammation in HS. These findings confirm a critical role of gasdermins in HS-related inflammation and identify pyroptosis as a promising therapeutic target. Further exploration of these pathways could yield valuable treatment strategies for managing this challenging skin condition.