2026/06/01 by Emma Holtappels, N. van Uden, Saskia Chielie +5 · 1 voice
Biochemistry, Genetics and Molecular Biology · Immunology and Microbiology · Medicine · #Hair Growth and Disorders #Mast cells and histamine #melanin and skin pigmentation
paper · doi:10.1016/j.jid.2026.05.017
openalex publication_date 2026/06/01 · openalex created_date 2026/06/03 · openalex updated_date 2026/07/23
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 patients with vitiligo 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 did not change under treatment, revealed 5 proteins associated with repigmentation. Higher baseline levels of T-cell immunoglobulin and mucin domain 1, trefoil factor 3, and NACHT, LRR and PYD domains-containing protein 1 in blister-fluid and an increase of keratin type II cytoskeletal 5 in plasma under treatment, were associated with repigmentation. T-cell immunoglobulin and mucin domain 1 and trefoil factor 3 have immunosuppressive effects, while NACHT, LRR and PYD domains-containing protein 1 and keratin type II cytoskeletal 5 can stimulate melanogenesis. The NACHT, LRR and PYD domains-containing protein 1-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 the understanding of repigmentation in vitiligo and could guide future therapeutic strategies.