Microarray Gene Expression Analysis of Lesional Skin in Canine Vesicular Cutaneous Lupus Erythematosus ( VCLE )

ABSTRACT Background Vesicular cutaneous lupus erythematosus (VCLE) is a rare autoimmune disease in dogs and is considered the canine counterpart of human subacute cutaneous lupus erythematosus (SCLE). However, the molecular mechanisms underlying VCLE remain incompletely defined. Objective/Hypothesis To characterise gene expression changes in lesional skin from dogs with VCLE and identify immune pathways involved in disease pathogenesis. Animals Six client‐owned dogs with clinically and histopathologically confirmed VCLE, and five healthy control dogs. Materials and Methods Formalin‐fixed, paraffin‐embedded lesional and control skin samples were analysed using the NanoString nCounter Canine Immuno‐Oncology Panel, targeting 780 immune‐related genes. Data were normalised using geNorm‐selected housekeeping genes. Differential expression, cell type profiling and pathway enrichment analyses were also performed. Results Principal component analysis showed clear separation between VCLE and healthy control samples. A total of 491 differentially expressed genes were identified, including 439 upregulated and 52 downregulated genes ( p ‐adj < 0.05). Lesional skin showed marked upregulation of interferon‐stimulated genes ( CXCL10, IDO1, ISG15, IFIT1 ), cytotoxic molecules ( GZMB, PRF1, FASLG ), pro‐inflammatory chemokines ( CXCL8, CCL3, CCL4 ) and S100 family markers ( S100A12, S100A9, S100A8 ). Downregulated genes included DLA‐DQB1, ERBB4, CCL27, GATA3 and RORC . Cell type profiling demonstrated enrichment of CD8 + T cells, cytotoxic T cells, natural killer cells, dendritic cells, macrophages and neutrophils. Pathway enrichment analysis identified activation of interferon signalling, Janus kinase signal transducer and activator of transcription (JAK–STAT) signalling, chemotaxis and cytotoxic immune pathways. Conclusions and Clinical Relevance VCLE lesions feature a dominant interferon‐stimulated gene signature, with downstream activation of JAK–STAT signalling and cytotoxic lymphocyte‐mediated immune responses, suggesting that interferon and JAK–STAT signalling are potential therapeutic targets.