Vitiligo blood transcriptomics provides new insights into disease mechanisms and identifies potential novel therapeutic targets

摘要: Significant gaps remain regarding the pathomechanisms underlying autoimmune response in vitiligo (VL), where loss of self-tolerance leads to targeted killing melanocytes. Specifically, there is incomplete information alterations systemic environment that are relevant disease state. We undertook a genome-wide profiling approach examine gene expression peripheral blood VL patients and healthy controls context our previously published VL-skin profile. used several silico bioinformatics-based analyses provide new insights into mechanisms suggest novel targets for future therapy. Unsupervised clustering methods VL-blood dataset demonstrate “disease-state”-specific set co-expressed genes. Ontology enrichment analysis 99 differentially expressed genes (DEGs) uncovers down-regulated immune/inflammatory response, B-Cell antigen receptor (BCR) pathways, apoptosis catabolic processes VL-blood. There evidence both type I II interferon (IFN) playing role pathogenesis. interactome identify key associated transcriptional factors (TFs) from within (STAT1, STAT6 NF-kB), as well “hidden” (CREB1, MYC, IRF4, IRF1, TP53) potentially affect The TFs overlap with reported lesional-skin circuitry, underscoring their potential importance disease. also shared -skin “hot spot” maps chromosome 6, includes three dysregulated (PSMB8, PSMB9 TAP1) described VL-associated genetic susceptibility loci. Finally, we support prioritizing or skin therapeutic targets. examined transcriptome (previously published) profile address major gap knowledge changes skin-specific manifestation vitiligo. Several spots” observed environments offer prioritized identifying risk framework VL, five molecules PRKCD, PTPN6, MYC FGFR2) lend themselves being by drugs VL-therapy.