Proteomic analysis of non-segmental vitiligo identifies immune- and keratinocyte-associated protein alterations

Vitiligo is an immune-mediated disease characterized by depigmentation of the skin. While transcriptomic studies have advanced the mechanistic understanding of the disease, comprehensive proteomic characterization of vitiligo-affected skin is lacking. This study aimed to investigate proteomic alterations in non-segmental vitiligo. Punch biopsies (2 mm) were collected from lesional (n=10), perilesional (n=62), and non-lesional skin (n=62) from patients with vitiligo, and from demographically matched (age, sex, and anatomical site) healthy controls (n=12). Proteomic profiling was performed using mass spectrometry, and data were analyzed in pairwise comparisons. The proteomic analyses quantified a total of 4,556 proteins, including 40 differentially expressed proteins (DEPs; false discovery rate<0.05). The comparison between lesional and healthy skin revealed the highest number of DEPs, predominantly associated with inflammatory and immune-related processes, including TNF-α signaling, complement pathways, and signal transducer and activator of transcription 6 (STAT6) signaling. Comparison between lesional and non-lesional skin showed differences in protein quantification related to melanocyte differentiation and keratinocyte stress responses. These proteins included protein O-fucosyltransferase 1 (POFUT1), involved in melanocyte development via Notch-1 signaling, and keratin 6B (KRT6B), implicated in keratinocyte migration during wound repair. This study provides insights into vitiligo pathophysiology, identifying proteins that, to our knowledge, have not previously been associated with vitiligo.