Minimally invasive 1 mm skin biopsies capture site-specific transcriptomic heterogeneity in vitiligo

BackgroundVitiligo is a chronic inflammatory skin disease characterized by clinical and molecular heterogeneity across lesional, perilesional and non-lesional skin within the same individual. Understanding these region-specific differences is essential for identifying early disease processes and developing targeted therapeutic strategies.

Skin biopsies represent a key approach to explore these differences, yet conventional 3–5 mm biopsies are invasive, requiring sutures, extended healing time and leaving visible scarring.ObjectivesThe objective of this study was to characterize region-specific transcriptomic alterations across lesional, perilesional, and non-lesional skin in vitiligo, using minimally invasive 1 mm skin punch biopsies.MethodsIn this study, bulk RNA sequencing was performed on 105 skin biopsies obtained from perilesional and (non-)lesional skin of non-segmental vitiligo patients, as well as healthy control skin. Differential gene expression was followed by pathway-level analyses, and Connectivity Map–based perturbational profiling was performed to predict candidate therapeutic compounds capable of reversing the lesional transcriptional signature.ResultsTranscriptomic profiling of 1 mm biopsies revealed disease-associated changes across lesional, perilesional, and non-lesional vitiligo skin, with distinct region-specific gene signatures reflecting immune activation and metabolic reprogramming.