Immunophenotyping and investigation of antigenic responses of peripheral blood cells in glycine receptor antibody positive cryptogenic focal epilepsy

Epilepsy is a common disease characterized by seizures caused by spontaneous, sudden electrical discharges in the brain. In some autoimmune diseases accompanied by seizures, it is thought that autoantibodies detected in serum and cerebrospinal fluids trigger epileptiform activity due to T cell mediated immune response in unknown etiology. Recently, the presence of glycine receptor (GlyR) antibodies, which are detected in patients with progressive encephalomyelitis with rigidity and myoclonus (PERM) also in cryptogenic focal epilepsy suggests that GlyR antibodies may play a role in the pathogenesis of seizures. To determine potential alterations in antigen-specific immune cell subpopulations of GlyR antibody positive epilepsy patients, a total of 22 Cryptogenic Focal Epilepsy patients with 7 GlyR antibody positive, and 15 antibody negative patients and 25 age and sex matched healthy individuals were included in this study. Peripheral blood mononuclear cells (PBMC) were isolated from the patients' blood, and immune system cells (NK cells, T cells with subgroups and B cells with subgroups) were labeled with fluorochrome antibodies and immunophenotyping was performed by flow cytometry. As a result of the study, there was no significant difference between the groups in the general population of B, T, NK and NKT cells. While naive B cells (CD19+IgD+CD27-) of GlyR antibody negative cases increased compared to healthy controls (p=0.0233), no significant difference was found in GlyR antibody positive cases. Both GlyR antibody positive and negative cases (CD19+IgD-CD27-) showed a decrease in immature B cells and significant difference was found in antibody negative cases (p=0.0458). The decrease in plasma (CD19+CD38+CD138+) and (CD19+CD38 ++CD138-) plasmablast cells of patients was not significant. No significant difference was found in CD4+ helper T cells and CD8+ cytotoxic T cells compared to controls. CD3+CD4+CD25+ T cells (p=0.0178) and CD3+CD4+CD25high regulator T cells (p=0.0101) increased in GlyR antibody positive patients compared to healthy volunteers. The findings support the view that GlyR antibodies may play a role in the pathogenesis of epilepsy by contributing to T cell-mediated active inflammation, a key mechanism in the development of autoimmunity.