Proteome profiling of cerebrospinal fluid-derived extracellular vesicles reveals potential biomarkers for drug-resistant epilepsy
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ABSTRACT: We utilised a spontaneous canine epilepsy model to study the proteomic content of CSF-derived EVs as a source of biomarkers for drug-resistant epilepsy (DRE). We included 37 drug-naïve dogs with recent onset epilepsy and confirmed diagnosis of idiopathic epilepsy. CSF samples were collected at the onset of epilepsy. After the first visit, antiseizure medication (ASM) treatment was started in all dogs and the dogs were followed up for at least 12 months. After the follow-up period, based on their response to ASM treatment, dogs were grouped as either drug-responsive or drug-resistant. We isolated CSF-derived EVs with ultrafiltration combined with size-exclusion chromatography and used nanoparticle tracking analysis (NTA) to study the number of particles. Proteomic analysis was then performed with liquid chromatography-tandem mass spectrometry. A comparison between the drug-responsive and drug-resistant dogs was conducted regarding CSF-derived EV proteomic data. NTA showed no significant difference in particle number between the groups. The proteomic analysis of normalised data identified five proteins with differential abundance between the two groups: KRT4, an uncharacterised immunoglobulin-like domain-containing protein (IgDCPa), F2, DSC1b, and LOC607874. A receiver operating characteristic analysis was performed, revealing a predictive value of ≥0.90 for two combinations of three proteins (KRT4, IgDCPa, and F2 (area under curve (AUC)=0.91, confidence interval (CI)=0.78-1.00); DSC1b, F2, and IgDCPa (AUC=0.90, CI=0.78-1.00)).
INSTRUMENT(S):
ORGANISM(S): Canis Lupus
TISSUE(S): Cerebrospinal Fluid
SUBMITTER:
Tuula Nyman
LAB HEAD: Tuula Nyman
PROVIDER: PXD061528 | Pride | 2025-12-22
REPOSITORIES: Pride
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