Li Xiaolong, Qin Xiaoxiao, Xie Yuan, Wang Lingyun, Wang Jinwen, Ji Shushen, Jiang Huihui, Wang Qun
Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Department of Neurology, Xiangyang No. 1 People's Hospital, Hubei University of Medicine, Xiangyang, Hubei, China.
CNS Neurosci Ther. 2025 Jan;31(1):e70203. doi: 10.1111/cns.70203.
Metabolomics offers promise in uncovering potential biomarkers and understanding the pathophysiology of autoimmune encephalitis (AE), which is a cluster of disorders with the host immune system targeting self-antigens expressed in the central nervous system (CNS). In this research, our objective was to explore metabolic characterization in cerebrospinal fluid (CSF) from individuals with AE, aiming to shed light on the pathophysiology of AE.
A targeted approach was applied using an ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) system to study CSF metabolites in patients with AE (n = 18), and control subjects without neurological diseases (n = 17).
A total of 21 potential biomarkers were acquired by getting the intersection of the differential metabolites from univariate statistics and multidimensional statistics between the AE (cell-based assay panel, CBA-panel) group and the control group. Specifically, the levels of pyruvic acid and oxoglutaric acid were notably elevated in the AE(CBA-panel) group compared to those in the control group, indicating that the dysregulated TCA cycle may play a pivotal role in the progression of AE(CBA-panel). Interestingly, 27 potential biomarkers were acquired by getting the intersection of the differential metabolites from univariate statistics and multidimensional statistics between the anti-N-methyl-D-aspartate receptor encephalitis (NMDARE) group and the control group, suggesting that the disparities between patients with greater homogeneity and the controls are amplified. In addition, seven differential metabolites were identified by the univariate statistics between the AE (tissue-based assay, TBA) group and the control group, including alpha-linolenic acid and gamma-linolenic acid, suggesting that dysregulated biosynthesis of unsaturated fatty acids and alpha-linolenic acid metabolism might be crucial in the AE(TBA) disease course.
Collectively, distinct metabolic profiles were evident in the CSF of the AE group compared to the control group, notably involving metabolites associated with mitochondrial dysfunction, which helped to elucidate the pathophysiology of AE.
代谢组学有望揭示潜在的生物标志物，并有助于理解自身免疫性脑炎（AE）的病理生理学机制。AE是一组疾病，其宿主免疫系统针对中枢神经系统（CNS）中表达的自身抗原。在本研究中，我们的目的是探索AE患者脑脊液（CSF）中的代谢特征，以阐明AE的病理生理学机制。
采用靶向方法，使用超高效液相色谱-串联质谱（UPLC-MS/MS）系统研究AE患者（n = 18）和无神经系统疾病的对照受试者（n = 17）的脑脊液代谢物。
通过获取AE（细胞检测面板，CBA面板）组与对照组之间单变量统计和多变量统计的差异代谢物的交集，共获得21种潜在生物标志物。具体而言，与对照组相比，AE（CBA面板）组中丙酮酸和酮戊二酸水平显著升高，表明三羧酸循环失调可能在AE（CBA面板）的进展中起关键作用。有趣的是，通过获取抗N-甲基-D-天冬氨酸受体脑炎（NMDARE）组与对照组之间单变量统计和多变量统计的差异代谢物的交集，获得了27种潜在生物标志物，这表明同质性更高的患者与对照组之间的差异被放大了。此外，通过AE（组织检测，TBA）组与对照组之间的单变量统计鉴定出7种差异代谢物，包括α-亚麻酸和γ-亚麻酸，表明不饱和脂肪酸生物合成失调和α-亚麻酸代谢可能在AE（TBA）病程中起关键作用。
总体而言，与对照组相比，AE组脑脊液中明显存在不同的代谢谱，尤其涉及与线粒体功能障碍相关的代谢物，这有助于阐明AE的病理生理学机制。
