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Abstract
Meningoencephalitis of unknown origin (MUO) is a common disorder in dogs that results in mononuclear inflammation of the brain and/or spinal cord. Granulomatous meningoencephalomyelitis (GME) and necrotizing meningoencephalitis (NME) are the two most commonly diagnosed variants. We hypothesized that the transcriptomic profiles for each would highlight both similarities and differences in inflammatory and immunological processes when compared to controls. We utilized unbiased next-generation RNA sequencing to test this hypothesis on brain tissue from dogs with GME (n=3), NME (n=3), and non-neurological illness (n=3). We found a total of 4,213 differentially expressed genes (DEGs) in GME and 1441 DEGs in NME when compared to controls, the majority of which were upregulated. However, when comparing GME to NME, there were only 222 DEGs identified and we did not find a subset of genes able to reliably distinguish GME from NME. Gene set enrichment analysis confirmed the immune system was overrepresented, with enrichment in the innate and adaptive branches, as well and T and B cell activation. Comparison of genes with an autoimmune database identified 88 and 69 genes in GME and NME, respectively, that are associated with 10 or more autoimmune diseases in humans. Future investigations with larger sample sizes are warranted, but our findings support the possibility of MUO as an autoimmune disease and provided several genes and pathways that can be targeted in future research.