成人耐药性癫■血清神经丝轻链水平与Th17/Treg失衡的关系

Relationship between Serum sNfL Level and Th17/Treg Imbalance in Adult Patients with Drugresistant Epilepsy

目的探讨成人耐药性癫■(DRE)血清神经丝轻链(sNfL)水平变化以及与辅助性T细胞17(Th17)/调节性T细胞(Treg)失衡的关系。方法收集2017年6月至2019年7月收治的99例成年癫■患者(癫■组)的临床资料,诊断为局灶性癫■病程≥1年。依据癫■发作情况分为控制良好癫■亚组[WCE亚组(42例)]和DRE亚组(57例)。另选择同时期体检中心招募的非癫■志愿者作为对照组(50例)。采用流式细胞术、多重免疫检测和超灵敏单分子阵列检测外周血单个核细胞中Th17和Treg频率、血清细胞因子和sNfL水平。结果与对照组比较,WCE亚组Th17频率、血清白细胞介素(IL)-17A、IL-1β和IL-6水平升高(均P<0.05);Treg频率、IL-10、转化生长因子β(TGF-β)和sNfL水平差异均无显著性(均P>0.05)。与对照组和WCE亚组比较,DRE亚组Th17频率、IL-17A、IL-1β、IL-6和sNfL水平升高;Treg频率、IL-10和TGF-β水平降低(均P<0.05)。相关性分析提示DRE亚组的血清sNfL水平与年龄、Th17频率、Th17/Treg比值、IL-17A、IL-1β和IL-6水平均呈正相关性(P<0.05)。结论DRE患者外周血中Th17比例增加,导致IL-17A、IL-1β、IL-6和sNfL水平升高,为DRE患者存在潜在的炎症和退行性生物标志物提供了证据。

Aim To investigate the levels of serum neurofilament light chain(sNfL),a marker of neuronal injury,and its relationship with helper T cell 17(Th17)/regulatory cell(Treg)imbalance in adult patients with drug-resistant epilepsy(DRE).Methods From June 2017 to July 2019,99 adult patients with epilepsy were enrolled.The patients were diagnosed as focal epilepsy for more than one year.They were divided into a well-controlled epilepsy group(WCE group,42 cases)and a DRE group(57 cases).And non-epileptic volunteers(50 cases)matched with the sex and age of epileptic patients were recruited from the physical examination center at the same time.Th17 and Treg cell frequency in peripheral blood mononuclear cells,serum cytokines,and sNfL levels were measured by flow cytometry,multiplex immunoassays,and ultrasensitive single molecule array.Results Compared with the control group,Th17 cell frequency,serum interleukin-17A(IL-17A),IL-1βand IL-6 were increased in WCE group(P<0.05),but Treg cell frequency,serum IL-10,transforming growth factor-β(TGF-β)and sNfL levels were not significantly different(P>0.05).But compared with the control group and WCE group,Th17 cell frequency,serum IL-17A,IL-1β,IL-6 and sNfL levels in DRE group increased,while serum Treg cell frequency,serum IL-10 and TGF-βlevels decreased(P<0.05).In DRE group,serum sNfL level was positively correlated with age,Th17 cell frequency,Th17/Treg ratio,IL-17A,IL-1βand IL-6 levels(P<0.05).Conclusion Increased Th17 cell ratio in peripheral blood of DRE patients resulted in increased levels of circulating pro-inflammatory cytokines(IL-17A,IL-1β,IL-6)and sNfL(a marker of neuronal injury),which provides the evidence for novel potential inflammatory and degenerative biomarkers in DRE.