Abstract

Purpose Previous studies have demonstrated that immune and inflammatory factors play an important role in recurrent seizures. The PD-1-PD-L pathway plays a central and peripheral immunosuppressive role by regulating multiple signaling pathways during the inflammatory and immunologic processes. This study is aimed at assessing PD-1 levels in cerebrospinal fluid (CSF) and serum samples from patients with intractable epilepsy. Methods PD-1 levels were assessed in CSF and serum samples from 67 patients with intractable epilepsy (41 and 26 individuals with partial seizure and intractable status epilepticus, respectively) and 25 healthy controls, using flow cytometric analysis and sandwich enzyme-linked immunosorbent assays (ELISA). Results Serum-PD-1+CD4+CD25high Treg levels in the experimental groups and the control group were 10.26 ± 2.53 (PS group), 35.95 ± 27.51 (ISE group), and 4.69 ± 2.44 (control group). In addition, CSF-PD-1 level in patients with epilepsy was higher than that in the control group (50.45 ± 29.56 versus 19.37 ± 4.51), indicating a statistically significant difference (P < 0.05). Interestingly, serum- and CSF-PD-1 levels in individuals with epilepsy were not affected by antiepileptic drug and treatment course, but by epilepsy onset level. Of note, the increase of CSF- and serum-PD-1 levels was more pronounced in subjects with intractable status epilepticus than those with partial seizure. Conclusion Serum- and CSF-PD-1 levels constitute a potential clinical diagnostic biomarker for intractable epilepsy and could also be used for differential diagnosis.

Highlights

  • Epilepsy is a common, serious chronic neurological disease [1] associated with stigma, psychiatric comorbidity, and high economic costs that caused the 56.79 per 100,000 personyears of incidence rate of epilepsy and affects about 50 million people worldwide [2]

  • We found lymphocyte ratio was decreased and PD-1+CD4+CD25high Treg level was increased in the patients with intractable epilepsy (IE), compared with controls (Figure 4(a), Table 2.2)

  • We found mild inflammation in patients with IE; both IL-6 and IL-10 were increased in serum samples (Figures 2(d) and 2(e), Table 1.2)

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Summary

Introduction

Serious chronic neurological disease [1] associated with stigma, psychiatric comorbidity, and high economic costs that caused the 56.79 per 100,000 personyears of incidence rate of epilepsy and affects about 50 million people worldwide [2]. Dozens of antiepileptic drugs (AEDs) have been developed and have good efficacy on epileptic seizures; approximately 20%-30% of patients remain untreated and often experience side effects [3, 4]. The positive rate of electroencephalogram is very low so it is difficult to diagnose epilepsy in clinic. The imbalance between excitatory and inhibitory neurotransmission and the formation of abnormal epilepsy network are accepted as the common mechanism of various epileptic seizures. With the exploration of pathogenesis of epilepsy, a large number of evidences show that recurrent seizures may be related to nonneural changes in recent years, but infections and infestations are among the most common risk factors for seizures and acquired epilepsy [5,6,7,8,9].

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