Early Proteomic Alterations in Non-segmental Vitiligo Skin Following Treatment with Topical Tacrolimus

INTRODUCTION: Vitiligo is a chronic depigmenting skin disease that can severely affect quality of life. First-line treatments include topical calcineurin inhibitors such as tacrolimus, but their molecular mechanisms of action in vitiligo remain incompletely understood. In this study, we investigated the early proteomic changes in patients with non-segmental vitiligo treated with topical tacrolimus. METHODS: We included eight patients and collected 2-mm punch biopsies from untreated lesional skin (LS) and nonlesional skin (NLS), as well as from LS skin after 2 and 8 weeks of treatment. Samples were analyzed with mass spectrometry-based proteomics. We used a pairwise comparison between untreated LS and NLS, and linear mixed models to compare untreated LS and tacrolimus-treated LS. RESULTS: In total, 4416 proteins were identified. Comparison between untreated LS and NLS revealed 32 differentially expressed proteins (DEPs; false discovery rate < 0.05), primarily associated with muscle contraction and melanocyte function. After 2 weeks of treatment, LS showed enrichment of 31 DEPs related to acute inflammatory responses and melanocyte adhesion, while LS treated for 8 weeks showed enrichment of 14 DEPs involved in melanogenesis, interferon-induced inflammation, and heat shock responses. CONCLUSION: This study characterizes the early proteomic response of the skin to tacrolimus treatment and offers insights into disease-associated proteins in vitiligo.