Regulatory T-cells in children with generalized epilepsy: a case-control study

Epilepsy is a chronic neurological disorder characterized by recurrent seizures, with emerging evidence suggesting a role for immune dysregulation, particularly involving regulatory T-cells (Tregs), in its pathogenesis. However, data on the Tregs profile in children with generalized epilepsy remain limited. This study aimed to compare peripheral Tregs levels and immune profiles in a cohort of Egyptian children with newly diagnosed generalized epilepsy to those of healthy controls. A case-control study was conducted involving 45 children with epilepsy and 45 healthy controls. Tregs and other immune markers were quantified using multicolor flow cytometry. Serum concentrations of IL-10, IL-6, IFN-γ, TNF-α, and IL-1β were measured via ELISA. Children with epilepsy exhibited significantly lower percentages of CD4 + CD25 + highFoxp3⁺ Tregs (1.95% ± 0.7%) compared to controls (3.1% ± 0.9%, p < 0.001). Additionally, CD4⁺ T-cells were reduced (34% ± 2.9% vs. 41.2% ± 3.7%, p = 0.01), whereas CD8⁺ T-cells, B-cells, and natural killer (NK) cells were elevated in the epilepsy group. IL-10 and pro-inflammatory cytokines (IL-1β, TNF-α, IFN-γ, IL-6) were significantly higher in the epilepsy group than in controls.

Immune dysregulation, characterized by reduced Tregs percentages and altered lymphocyte distribution, and a dual pro-inflammatory/anti-inflammatory cytokine profile, may be associated with the pathophysiology of generalized epilepsy in children. Our results support further investigations into immunomodulatory strategies targeting Tregs restoration as potential disease-modifying interventions.

• Regulatory T-cells (Tregs) deficiency and pro-inflammatory cytokine elevation are reported in pediatric epilepsy, implicating immune dysregulation in disease pathogenesis. • IL-10 is frequently elevated in epilepsy, suggesting a compensatory anti-inflammatory response, though its functional role (protective vs. exhausted) remains unclear.

• In newly diagnosed, drug-naïve children with generalized epilepsy, Tregs' deficiency is accompanied by a distinct peripheral immune signature: reduced CD4⁺, elevated CD8⁺, NK, and B-cells, alongside a dual pro-/anti-inflammatory cytokine profile. • This immune dysregulation is present at disease onset-unconfounded by antiseizure drugs or chronicity-establishing Tregs' restoration as a potential disease-modifying intervention.