Immune and Biological Changes during Treatment in Patients with Nonsegmental Vitiligo and their Relation to Repigmentation

The treatment of nonsegmental vitiligo remains challenging and poorly understood. The aim of this study was to evaluate protein differences in lesional and nonlesional skin and changes of cellular and proteomic markers early in treatment in lesional skin and blood in relation to clinical response. This prospective exploratory study was conducted in 30 patients with nonsegmental vitiligo, 11 starting with standard-of-care topical therapy and 19 starting in combination with narrow-band UVB phototherapy. We identified 53 proteins that differed between blister fluids from lesional and nonlesional skin before treatment. After 3 months of therapy, CD3⁺, CD8⁺ T, and tissue-resident memory (CD69⁺CD103^-) cell populations decreased in skin biopsies, together with changes in 47 blister fluid proteins. Percentages of circulating follicular T helper type 17, CD336⁺Nk^bright, type 1 regulatory T (Tr1), and IL-10-secreting Tr1 cells decreased in blood. Decreases in tissue-resident memory, Tr1, and IL-10-secreting Tr1 cells and fatty acid-binding protein 4 were associated with repigmentation, measured by Vitiligo Extent Score at baseline and 6 months. Differences in lesional and nonlesional skin prior to treatment do not reflect changes in lesional skin early in therapy nor associations with clinical repigmentation response. We found an association between decreasing fatty acid-binding protein 4 and tissue-resident memory cells in the skin and IL-10-secreting Tr1 cells in the blood and repigmentation response to treatment of vitiligo.