SV2A expression in blood cells as a possible biomarker candidate for levetiracetam treatment response

This study was undertaken to evaluate whether synaptic vesicle protein 2A (SV2A) expression on peripheral immune cells predicts treatment response to levetiracetam in epilepsy.

High-dimensional flow cytometry was used to prospectively assess SV2A expression on immune cells from levetiracetam responders, nonresponders, and healthy controls. SV2A expression levels were further validated using real-time quantitative polymerase chain reaction (RT-qPCR) in an independent retrospective cohort. The predictive value of SV2A expression on naive CD8⁺ T cell-specific SV2A/CD3⁺ median fluorescence intensity (MFI) ratio was determined, and correlations with central nervous system (CNS)-resident cell expression were examined in the wild-type (WT) C57BL6 mouse model.

Naive CD8⁺ T cells showed significantly lower SV2A expression (p = .0029) in nonresponders compared to responders, confirmed by RT-qPCR (p = .0022), with no difference in overall CD8⁺ T-cell abundance. The naive CD8⁺ T cell-specific SV2A/CD3⁺ MFI ratio (>.4733) correctly identified most responders, with a positive predictive value of 81.8%. SV2A concentration was stable over time (mean interval = 121.2 days, 95% confidence interval = 93.64-148.7 days), unaffected by age, gender, dose, or treatment duration, and neuronal SV2A expression in the CNS of WT C57BL6 mice correlated with SV2A expression of CD8⁺ in circulating blood cells (r = .655, p = .008).

Naive CD8+ T cell-specific SV2A MFI ratio may represent a potential indicator of treatment response for levetiracetam. Pending further validation, its stability and accessibility suggest that it could potentially support treatment decisions and help to reduce ineffective drug trials.