Circulating P2X7 Receptor Signaling Components as Diagnostic Biomarkers for Temporal Lobe Epilepsy.

Giorgia Conte,Tobias Engel,David C Henshall,Hany El-Naggar,Mariana Alves,Felix Rosenow,Aida Menéndez-Méndez,Annette Nicke,Sebastian Bauer,Norman Delanty

doi:10.3390/cells10092444

Abstract

Circulating molecules have potential as biomarkers to support the diagnosis of epilepsy and to assist with differential diagnosis, for example, in conditions resembling epilepsy, such as in psychogenic non-epileptic seizures (PNES). The P2X7 receptor (P2X7R) is an important regulator of inflammation and mounting evidence supports its activation in the brain during epilepsy. Whether the P2X7R or P2X7R-dependent signaling molecules can be used as biomarkers of epilepsy has not been reported. P2X7R levels were analyzed by quantitative ELISA using plasma samples from controls and patients with temporal lobe epilepsy (TLE) or PNES. Moreover, blood cell P2X7R expression and P2X7R-dependent cytokine signature was measured following status epilepticus in P2X7R-EGFP reporter, wildtype, and P2X7R-knockout mice. P2X7R plasma levels were higher in TLE patients when compared with controls and patients with PNES. Plasma levels of the broad inflammatory marker protein C-Reactive protein (CRP) were similar between the three groups. Using P2X7R-EGFP reporter mice, we identified monocytes as the main blood cell type expressing P2X7R after experimentally evoked seizures. Finally, cytokine array analysis in P2X7R-deficient mice identified KC/GRO as a potential P2X7R-dependent plasma biomarker following status epilepticus and during epilepsy. Our data suggest that P2X7R signaling components may be a promising subclass of circulating biomarkers to support the diagnosis of epilepsy.

Highlights

Epilepsy is a common chronic neurological disease, affecting up to 70 million people worldwide [1]
Plasma samples were obtained from healthy controls and patients admitted to two different epilepsy centers which included Marburg (Germany, MAR) and Dublin (Ireland, DUB) (Figure 1A and Supplementary Table S1)
P2X7 receptor (P2X7R) plasma levels were higher in baseline samples from patients with temporal lobe epilepsy (TLE) (242.6 ± 39.2 pg/mL) compared with controls and levels remained elevated in samples collected 1 h following an EEG-detected seizure (302.1 ± 86.3 pg/mL)

Summary

Introduction

Epilepsy is a common chronic neurological disease, affecting up to 70 million people worldwide [1]. Temporal lobe epilepsy (TLE) is one of the most common and drugrefractory form of epilepsy in adults [1]. Together with the lack of effective pharmacological approaches in over 30% of patients and the absence of disease-modifying treatments, 4.0/). Epilepsy diagnosis remains a clinical challenge, adding significantly to the disease burden [1,2]. While a correct diagnosis of epilepsy is important to inform treatment, to date, epilepsy diagnosis relies heavily on clinical examination, history, and patient monitoring via long-term video-encephalogram (vEEG) recording at hospitals. Long-term EEG recordings are, time-consuming, costly, have low throughput, and require a high level of specialist expertise [3]. There is significant interest in the discovery and validation of circulating (molecular) biomarkers to identify patients with epilepsy [5]

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Results

Conclusion