Presence of anti-TRIM46-autoantibodies in serum and cerebrospinal fluid from a dog presenting with meningoencephalomyelitis of unknown origin

In humans, autoimmune encephalitides (AE) are a group of inflammatory conditions in which autoantibodies (AABs) targeting CNS neurons are present. AE can be divided into two subgroups based
on antigen location; 1) antigens are located extracellularly, and AABs are pathogenic - for this subgroup, prognosis is often good, or 2) antigens are located intracellularly, and cytotoxic T-cells cause disease, with AABs being present, but not pathogenic. The latter subtype is often paraneoplastic and
carries a poor prognosis. AABs with an intracellular neuronal target have not previously been reported in dogs. Methods: A broad investigation for AABs targeting neuronal tissue was performed using CSF and serum from an
8-year-old Labrador Retriever (male, entire) diagnosed with meningoencephalitis of unknown origin based on exclusion of infectious diseases, and findings on MRI and CSF-analysis. Cell-based (EUROIMMUN, ‘Autoimmune Encephalitis Mosaic 6’ and ‘Anti-Glutamic Acid Decarboxylase 65 kDa’) and tissue-based (EUROIMMUN, ‘Mosaic: Cerebellum (Rat)/Hippocampus (Rat)’) indirect
immunofluorescence (IIF) assays were used. Results: Cell-based IIF assays were negative. On tissue-based IIF assays, fluorescence in the axon initial segment
was detected in both serum and CSF, consistent with the pattern seen in humans suffering from antitripartite motif-containing 46 (TRIM46)-encephalitis – an intracellular, often paraneoplastic, AE. A cellbased assay (EUROIMMUN, research use only, TRIM46 transfected cells) confirmed the presence of antiTRIM46-AABs.
Discussion/conclusion: This is the first case identifying an intracellular neuronal target for AABs in dogs. Future studies investigating for AABs targeting CNS in dogs should include TRIM46 as a potential target.