Wang Kai, Yang Jinwei, Xu Wenhao, Wang Lei, Wang Yu
Department of Neurology, The Third Affiliated Hospital of Anhui Medical University, Hefei, China.
Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Front Aging Neurosci. 2024 Aug 7;16:1400426. doi: 10.3389/fnagi.2024.1400426. eCollection 2024.
Epilepsy is associated with the immune system and metabolism; however, its etiology remains insufficiently understood. Here, we aim to elucidate whether circulating immune cell profiles and metabolites impact the susceptibility to epilepsy.
We used publicly available genetic data and two-sample Mendelian randomization (MR) analyses to establish causal relationships and mediating effects between 731 immune cells and 1,400 metabolites associated with epilepsy. Sensitivity analyses were conducted to detect heterogeneity and horizontal pleiotropy in the study results.
MR analysis examining the relationship between immune cells, metabolites, and epilepsy revealed significant causal associations with 28 different subtypes of immune cells and 14 metabolites. Besides, the mediation effects analysis revealed that eight metabolites mediated the effects of six types of immune cells on epilepsy and that 3-hydroxyoctanoylcarnitine (2) levels exhibited the highest mediating effect, mediating 15.3% (95%CI, -0.008, -30.6%, = 0.049) of the effect of DN (CD4-CD8-) AC on epilepsy. 1-(1-enyl-stearoyl)-2-linoleoyl-GPE (p-18:0/18:2) levels (95%CI, 0.668, 10.6%, = 0.026) and X-12544 levels (95%CI, -15.1, -0.856%, = 0.028) contributed 5.63 and 8%, respectively, to the causal effect of FSC-A on myeloid DC on epilepsy.
This study revealed a significant causal link between immune cells, metabolites, and epilepsy. It remarkably enhances our understanding of the interplay between immune responses, metabolites, and epilepsy risk, providing insights into the development of therapeutic strategies from both immune and metabolic perspectives.
癫痫与免疫系统和代谢有关；然而，其病因仍未得到充分理解。在此，我们旨在阐明循环免疫细胞谱和代谢产物是否会影响癫痫易感性。
我们使用公开可用的遗传数据和两样本孟德尔随机化（MR）分析，以建立731种免疫细胞和1400种与癫痫相关的代谢产物之间的因果关系和中介效应。进行敏感性分析以检测研究结果中的异质性和水平多效性。
MR分析检查免疫细胞、代谢产物和癫痫之间的关系，发现与28种不同亚型的免疫细胞和14种代谢产物存在显著因果关联。此外，中介效应分析表明，8种代谢产物介导了6种免疫细胞对癫痫的影响，其中3-羟基辛酰肉碱（2）水平表现出最高的中介效应，介导了DN（CD4-CD8-）AC对癫痫影响的15.3%（95%CI，-0.008，-30.6%，P = 0.049）。1-（1-烯基-硬脂酰基）-2-亚油酰基-GPE（p-18:0/18:2）水平（95%CI，0.668，10.6%，P = 0.026）和X-12544水平（95%CI，-15.1，-0.856%，P = 0.028）分别对FSC-A对癫痫的髓样DC因果效应贡献了5.63%和8%。
本研究揭示了免疫细胞、代谢产物和癫痫之间存在显著因果联系。它显著增强了我们对免疫反应、代谢产物和癫痫风险之间相互作用的理解，从免疫和代谢角度为治疗策略的开发提供了见解。
