Badanie roli PD-1 jako markera epilepsji opornej na leki i jego potencjalne zastosowanie w leczeniu kwasem walproinowym
Exploring the role of PD-1 as a marker in drug-refractory epilepsy and its potential indication for valproic acid treatment
W skrócie
Badanie wykazało, że białko PD-1 jest podwyższone u pacjentów z epilepsją oporną na leki, szczególnie w ciężkich postaciach choroby, co sugeruje jego rolę jako markera diagnostycznego. Naukowcy odkryli, że lek zwany kwasem walproinowym (VPA) zmniejsza stężenie PD-1 i reguluje system odpornościowy, a jego skuteczność nie zależy od stężenia leku we krwi, lecz od wpływu na procesy immunologiczne w organizmie.
Oryginalny abstract (angielski)
BACKGROUND: The immune checkpoint pathway PD-1/PD-L, known for its role in immunosuppression via regulatory T cells (Tregs) and inflammatory signaling, is implicated in the neuroinflammation of drug-refractory epilepsy (DRE). Given the emerging importance of immune dysregulation in epilepsy, identifying immune-related biomarkers may improve diagnosis and guide treatment strategies. OBJECTIVE: This study aimed to evaluate the potential of PD-1 as a diagnostic biomarker in the cerebrospinal fluid (CSF) and plasma and to investigate whether the therapeutic effect of valproic acid (VPA) in intractable status epilepticus (ISE) is mediated through immunomodulation. METHODS: A cohort of 74 patients with DRE (46 with partial seizures (PS) and 28 with ISE) and 25 healthy controls was enrolled. PD-1 levels in CSF and plasma were quantified by flow cytometry and ELISA. In a VPA-treatment sub-study of 25 ISE patients, serial samples were analyzed for PD-1CD4CD25 Tregs and cytokine (IL-10/IL-6) levels at baseline (d0) and after 48 h (d3). VPA concentrations were determined by LC-MS/MS. RESULTS: Significantly elevated PD-1 levels were observed in both plasma and CSF of epilepsy patients compared to controls, with the highest levels in the ISE subgroup. IL-10 and IL-6 levels were also elevated in intractable epilepsy (IE) patients compared to controls. Critically, clinical improvement was associated with a reduction in PD-1 Tregs at d3, whereas VPA concentrations did not correlate with treatment response. These findings reveal a compartmentalized immune response, with peripheral immunosuppression and localized CNS immune activation in IE. CONCLUSION: These findings identify PD-1 as a promising immune-inflammatory biomarker for DRE and its severe forms. Moreover, they suggest that the efficacy of VPA in ISE is mediated through the modulation of the PD-1 pathway and related cytokines, rather than a direct concentration-dependent pharmacological effect.