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Microarray Gene Expression Analysis of Lesional Skin in Canine Vesicular Cutaneous Lupus Erythematosus (VCLE)
Treasa Keating1, Lauren Stranahan2, Dominique Wiener3
1Coastal Veterinary Dermatology and Ear Clinic, Houston, Texas, USA.
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.

