Abstract
BackgroundCanine idiopathic epilepsy (IE) is a common neurological disease with severe impact on the owner´s and the dog’s quality of life. A subpopulation of dogs with IE does not respond to antiseizure drugs (non-responder). Th17 cells (T helper cells) and their proinflammatory Interleukin-17 (IL-17) are part of the immune system and previous studies showed their involvement in the pathogenesis of several autoimmune diseases. Non-responder might have an abnormal immune response against structures of the central nervous system. To discover a new aetiology of canine IE and thereby optimising the therapy of intractable IE, this prospective study aimed to investigate Th17 cells and IL-17 in dogs with IE. The underlying hypothesis was that in some dogs with IE a Th17 cell-mediated immune response could be detectable.Methods57 dogs with IE and 10 healthy dogs (control group, C) were enrolled in the study. EDTA blood was taken to measure Th17 cells by flow cytometry. IL-17 was measured in 35 cerebrospinal fluid (CSF) and 33 serum samples using an enzyme-linked immunosorbent assay (ELISA). It was investigated whether there was a significant increase of stimulated Th17 cells in blood samples or of IL-17 in serum and CSF samples of dogs with IE in comparison to C. Correlations between the amount of Th17 cells/μL or IL-17 and different clinical parameters e.g. seizure frequency, seizure type, seizure severity or treatment response were evaluated. Additionally, Th17 cells/μL were randomly controlled of 17 dogs with IE and were examined for changes over time and in relation to treatment response.ResultsTen dogs with IE had strongly elevated stimulated Th17 cells/μL within the blood (>100 Th17 cells/μL). A slight positive correlation between stimulated Th17 cells/μL and seizure severity (p = 0.046; rSpear = 0.27) was proven in these dogs. In addition, 4/10 dogs with elevated Th17 levels experienced cluster seizures and status epilepticus in comparison to 9% of the dogs with non-elevated Th17 levels (<100 Th17 cells/μL). Dogs with IE had significantly higher IL-17 values in CSF and serum samples compared to C (p<0.001; p<0.002; respectively).ConclusionIn single dogs with IE, strongly increased amounts of Th17 cells were detectable and dogs with elevated Th17 cells seemed to have a greater risk for experiencing a combination of cluster seizures and status epilepticus. Therefore, an underlying Th17-cell mediated immune response was suspected and hence anti-inflammatory drugs could be indicated in these single cases with intractable epilepsy.
Highlights
In single dogs with idiopathic epilepsy (IE), strongly increased amounts of Th17 cells were detectable and dogs with elevated Th17 cells seemed to have a greater risk for experiencing a combination of cluster seizures and status epilepticus
An underlying Th17-cell mediated immune response was suspected and anti-inflammatory drugs could be indicated in these single cases with intractable epilepsy
Idiopathic epilepsy (IE) is divided by the „International Veterinary Epilepsy Task Force” (IVETF) into three groups: genetic epilepsy, suspected genetic epilepsy (a causative gene has not been identified, but there is a high prevalence in the breed (>2%)) and epilepsy of unknown cause [1]
Summary
Methods dogs with IE and10 healthy dogs (control group, C) were enrolled in the study. Th17 cells/μL were randomly controlled of 17 dogs with IE and were examined for changes over time and in relation to treatment response This prospective study was approved by the Animal Care Committee of the Government of Lower Saxony and national regulations for animal welfare (experiment number 33.8-4250205-18A290) and was performed with the owner’s informed written consent. T-test was used for normal distributed data and the Wilcoxon Two-Sample Test for non-normal distributed data It was investigated whether there were differences in the amount of Th17 cells and IL-17 in dogs with IE in comparison to dogs of the control group as well as whether there were correlations between Th17 cells and IL-17 and investigated clinical parameters (see Table 1). Spearmans correlation was used and the Fishers exact test was used to compare frequencies of qualitative clinical parameter definition
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