Revealing Biological Mechanisms of Skin Pigment Recovery during Treatment in Vitiligo Patients; A Proteomic Analysis

Vitiligo is an autoimmune disease characterized by depigmented skin lesions, caused by autoreactive-CD8-T-cells inducing melanocyte apoptosis. Effective treatment is challenging due to limited understanding of the processes underlying skin repigmentation. This study aimed to identify these processes using proteomics. Plasma and skin blister-fluid samples from 30 vitiligo patients starting standard-of-care treatment were analyzed. A large proteomic screen of 5080 proteins was measured with Somascan on samples collected at baseline and at 3-months of treatment. Analyses of proteins that changed and not changed under treatment, revealed 5 proteins associated with repigmentation. Higher baseline levels of TIM-1, TFF3 and NLRP1 in blister-fluid and an increase of KRT5 in plasma under treatment, were associated with repigmentation. TIM-1 and TFF3 have immunosuppressive effects, while NLRP1 and KRT5 can stimulate melanogenesis. The NLRP1-inflammasome pathway was enriched in these proteins. These proteins and pathways were distinct from the previously identified differences between lesional and non-lesional skin, indicating differential expression of melanocyte-specific pathways. This suggests that treatment-induced repigmentation in vitiligo involves processes other than simply reversing lesional skin to a non-lesional state. These findings enhance understanding of repigmentation in vitiligo and could guide future therapeutic strategies.