Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
Division of Neuroimmunology, Department of Neurology, Johns Hopkins University, Baltimore, MD, USA.
Mult Scler. 2023 Jul;29(8):936-944. doi: 10.1177/13524585231171517. Epub 2023 May 18.
The circulating metabolome is altered in multiple sclerosis (MS), but its prognostic capabilities have not been extensively explored. Lipid metabolites might be of particular interest due to their multiple roles in the brain, as they can serve as structural components, energy sources, and bioactive molecules. Gaining a deeper understanding of the disease may be possible by examining the lipid metabolism in the periphery, which serves as the primary source of lipids for the brain.
To determine if altered serum lipid metabolites are associated with the risk of relapse and disability in children with MS.
We collected serum samples from 61 participants with pediatric-onset MS within 4 years of disease onset. Prospective longitudinal relapse data and cross-sectional disability measures (Expanded Disability Status Scale [EDSS]) were collected. Serum metabolomics was performed using untargeted liquid chromatography and mass spectrometry. Individual lipid metabolites were clustered into pre-defined pathways. The associations between clusters of metabolites and relapse rate and EDSS score were estimated utilizing negative binomial and linear regression models, respectively.
We found that serum acylcarnitines (relapse rate: normalized enrichment score [NES] = 2.1, = 1.03E-04; EDSS: NES = 1.7, = 0.02) and poly-unsaturated fatty acids (relapse rate: NES = 1.6, = 0.047; EDSS: NES = 1.9, = 0.005) were associated with higher relapse rates and EDSS, while serum phosphatidylethanolamines (relapse rate: NES = -2.3, = 0.002; EDSS: NES = -2.1, = 0.004), plasmalogens (relapse rate: NES = -2.5, = 5.81E-04; EDSS: NES = -2.1, = 0.004), and primary bile acid metabolites (relapse rate: NES = -2.0, = 0.02; EDSS: NES = -1.9, = 0.02) were associated with lower relapse rates and lower EDSS.
This study supports the role of some lipid metabolites in pediatric MS relapses and disability.
多发性硬化症（MS）患者的循环代谢组发生改变，但尚未广泛探索其预后能力。脂质代谢物可能特别重要，因为它们在大脑中有多种作用，既是结构成分，又是能量来源和生物活性分子。通过检查作为大脑主要脂质来源的外周脂质代谢，可以更深入地了解疾病。
确定儿童 MS 患者血清脂质代谢物的改变是否与复发和残疾的风险相关。
我们在疾病发病后 4 年内收集了 61 名儿科起病 MS 患者的血清样本。收集了前瞻性纵向复发数据和横断面残疾测量（扩展残疾状况量表[EDSS]）。使用非靶向液相色谱和质谱法进行血清代谢组学分析。将个体脂质代谢物聚类为预先定义的途径。利用负二项式和线性回归模型分别估计代谢物簇与复发率和 EDSS 评分之间的关联。
我们发现血清酰基肉碱（复发率：归一化富集评分[NES] = 2.1， = 1.03E-04；EDSS：NES = 1.7， = 0.02）和多不饱和脂肪酸（复发率：NES = 1.6， = 0.047；EDSS：NES = 1.9， = 0.005）与更高的复发率和 EDSS 相关，而血清磷脂酰乙醇胺（复发率：NES = -2.3， = 0.002；EDSS：NES = -2.1， = 0.004）、血浆甘油磷脂（复发率：NES = -2.5， = 5.81E-04；EDSS：NES = -2.1， = 0.004）和初级胆汁酸代谢物（复发率：NES = -2.0， = 0.02；EDSS：NES = -1.9， = 0.02）与更低的复发率和更低的 EDSS 相关。
这项研究支持了一些脂质代谢物在儿科 MS 复发和残疾中的作用。
