Department of Biostatistics, University at Buffalo, The State University of New York at Buffalo, Buffalo, NY, USA.
Department of Biotechnical and Laboratory Sciences, University at Buffalo, The State University of New York at Buffalo, Buffalo, NY, USA.
Metabolomics. 2023 Apr 20;19(5):44. doi: 10.1007/s11306-023-02010-0.
Multiple sclerosis (MS) is a disease of the central nervous system associated with immune dysfunction, demyelination, and neurodegeneration. The disease has heterogeneous clinical phenotypes such as relapsing-remitting MS (RRMS) and progressive multiple sclerosis (PMS), each with unique pathogenesis. Metabolomics research has shown promise in understanding the etiologies of MS disease. However, there is a paucity of clinical studies with follow-up metabolomics analyses. This 5-year follow-up (5YFU) cohort study aimed to investigate the metabolomics alterations over time between different courses of MS patients and healthy controls and provide insights into metabolic and physiological mechanisms of MS disease progression.
A cohort containing 108 MS patients (37 PMS and 71 RRMS) and 42 controls were followed up for a median of 5 years. Liquid chromatography-mass spectrometry (LC-MS) was applied for untargeted metabolomics profiling of serum samples of the cohort at both baseline and 5YFU. Univariate analyses with mixed-effect ANCOVA models, clustering, and pathway enrichment analyses were performed to identify patterns of metabolites and pathway changes across the time effects and patient groups.
Out of 592 identified metabolites, the PMS group exhibited the most changes, with 219 (37%) metabolites changed over time and 132 (22%) changed within the RRMS group (Bonferroni adjusted P < 0.05). Compared to the baseline, there were more significant metabolite differences detected between PMS and RRMS classes at 5YFU. Pathway enrichment analysis detected seven pathways perturbed significantly during 5YFU in MS groups compared to controls. PMS showed more pathway changes compared to the RRMS group.
多发性硬化症（MS）是一种中枢神经系统疾病，与免疫功能障碍、脱髓鞘和神经退行性变有关。该疾病具有异质性的临床表型，如复发缓解型多发性硬化症（RRMS）和进展型多发性硬化症（PMS），每种疾病都有其独特的发病机制。代谢组学研究在理解 MS 疾病的病因方面显示出了一定的前景。然而，目前缺乏具有代谢组学随访分析的临床研究。本项为期 5 年的随访（5YFU）队列研究旨在探究不同 MS 患者病程和健康对照组之间随时间推移的代谢组学变化，并深入了解 MS 疾病进展的代谢和生理机制。
该队列包含 108 名 MS 患者（37 名 PMS 和 71 名 RRMS）和 42 名对照者，中位随访时间为 5 年。应用液相色谱-质谱联用（LC-MS）对队列的基线和 5YFU 时的血清样本进行非靶向代谢组学分析。采用混合效应 ANCOVA 模型、聚类和通路富集分析进行单变量分析，以识别随时间变化和患者组之间的代谢物和通路变化模式。
在 592 种鉴定出的代谢物中，PMS 组的变化最为明显，有 219 种（37%）代谢物随时间变化，132 种（22%）代谢物在 RRMS 组中发生变化（经 Bonferroni 校正 P<0.05）。与基线相比，在 5YFU 时 PMS 和 RRMS 组之间检测到更多的显著代谢物差异。通路富集分析发现，与对照组相比，MS 组在 5YFU 期间有 7 条通路发生了显著变化。与 RRMS 组相比，PMS 组显示出更多的通路变化。
