Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, University of Medicine and Health Sciences, D02 YN77 Dublin, Ireland.
Epilepsy Center Hessen, Department of Neurology, Philipps-University Marburg, Baldingerstr, 35043 Marburg, Germany.
Cells. 2021 Sep 16;10(9):2444. doi: 10.3390/cells10092444.
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.
循环分子有可能成为支持癫痫诊断和辅助鉴别诊断的生物标志物，例如在类似癫痫的情况下，如在精神性非癫痫性发作（PNES）中。P2X7 受体（P2X7R）是炎症的重要调节剂，越来越多的证据支持其在癫痫发作时在大脑中被激活。P2X7R 或 P2X7R 依赖性信号分子是否可以用作癫痫的生物标志物尚未报道。使用来自对照和颞叶癫痫（TLE）或 PNES 患者的血浆样本，通过定量 ELISA 分析 P2X7R 水平。此外，在 P2X7R-EGFP 报告基因、野生型和 P2X7R 敲除小鼠中，在癫痫持续状态后测量了血细胞 P2X7R 表达和 P2X7R 依赖性细胞因子特征。与对照和 PNES 患者相比，TLE 患者的 P2X7R 血浆水平更高。三组之间的广泛炎症标志物蛋白 C-反应蛋白（CRP）的血浆水平相似。使用 P2X7R-EGFP 报告基因小鼠，我们确定单核细胞是在实验性诱发癫痫后表达 P2X7R 的主要血细胞类型。最后，在 P2X7R 缺陷型小鼠中的细胞因子阵列分析鉴定 KC/GRO 为癫痫持续状态后和癫痫期间潜在的 P2X7R 依赖性血浆生物标志物。我们的数据表明，P2X7R 信号成分可能是支持癫痫诊断的有前途的循环生物标志物亚类。
