Neutrophil-associated extracellular DNA pathways in vitiligo: compartment-specific changes following combined fractional CO

Background: Vitiligo is a chronic inflammatory depigmenting skin disorder characterized by progressive loss of functional melanocytes, in which adaptive immune mechanisms, particularly T-cell-mediated responses, play a well-established role. Emerging evidence suggests that innate immune pathways, including neutrophil activation, oxidative stress, and dysregulation of neutrophil extracellular trap (NET)-associated processes, may also contribute to disease-associated inflammation. Methods: This study investigated NET-associated markers (MPO-DNA complexes, PAD-4, and DNase I) in patients with vitiligo before and after six months of combined fractional CO Results: At baseline, vitiligo patients exhibited elevated circulating MPO-DNA complexes and DNase I levels compared with healthy controls, whereas systemic PAD-4 levels were decreased. Lesional skin demonstrated increased expression of MPO, PAD-4, and DNase I compared with healthy skin. After six months of combined therapy, serum DNase I levels increased further, whereas lesional skin showed reduced MPO and PAD-4 expression together with a further increase in DNase I expression. Conclusions: These findings may indicate altered extracellular DNA handling and compartment-specific modulation of NET-associated pathways in vitiligo, although the functional significance of these changes remains unclear. Overall, the results suggest that NET-associated parameters may reflect local and systemic inflammatory changes associated with vitiligo and with treatment-related changes. Further studies are warranted to clarify the underlying mechanisms, validate these observations in larger longitudinal cohorts, and determine their potential relevance as indicators of disease-associated inflammatory activity.