Mass Spectrometry Center, QOPNA/LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, Campus Universitário de Santiago, 3810-193, Aveiro, Portugal; CESAM, Centre for Environmental and Marine Studies, Department of Chemistry, University of Aveiro, Campus Universitário de Santiago, 3810-193, Aveiro, Portugal.
Health Sciences Research Centre, Universidade da Beira Interior (CICS-UBI), Avenida Infante D. Henrique, Covilhã, 6200-506, Portugal; Serviço Patologia Clínica, Centro Hospitalar Cova da Beira, Quinta do Alvito, 6200-251 Covilhã, Portugal.
Arch Biochem Biophys. 2021 Jan 15;697:108672. doi: 10.1016/j.abb.2020.108672. Epub 2020 Nov 12.
Multiple sclerosis is a neurodegenerative disease causing disability in young adults. Alterations in metabolism and lipid profile have been associated with this disease. Several studies have reported changes in the metabolism of arachidonic acid and the profile of fatty acids, ceramides, phospholipids and lipid peroxidation products. Nevertheless, the understanding of the modulation of circulating lipids at the molecular level in multiple sclerosis remains unclear. In the present study, we sought to assess the existence of a distinctive lipid signature of multiple sclerosis using an untargeted lipidomics approach. It also aimed to assess the differences in lipid profile between disease status (relapse and remission). For this, we used hydrophilic interaction liquid chromatography coupled with mass spectrometry for phospholipidomic profiling of serum samples from patients with multiple sclerosis. Our results demonstrated that multiple sclerosis has a phospholipidomic signature different from that of healthy controls, especially the PE, PC, LPE, ether-linked PE and ether-linked PC species. Plasmalogen PC and PE species, which are natural endogenous antioxidants, as well as PC and PE polyunsaturated fatty acid esterified species showed significantly lower levels in patients with multiple sclerosis and patients in both remission and relapse of multiple sclerosis. Our results show for the first time that the serum phospholipidome of multiple sclerosis is significantly different from that of healthy controls and that few phospholipids, with the lowest p-value, such as PC(34:3), PC(36:6), PE(40:10) and PC(38:1) may be suitable as biomarkers for clinical applications in multiple sclerosis.
多发性硬化症是一种导致年轻人残疾的神经退行性疾病。代谢和脂质谱的改变与这种疾病有关。几项研究报告了花生四烯酸代谢和脂肪酸、神经酰胺、磷脂和脂质过氧化产物谱的变化。然而，多发性硬化症患者循环脂质在分子水平上的调节机制仍不清楚。在本研究中，我们试图采用非靶向脂质组学方法评估多发性硬化症是否存在独特的脂质特征。它还旨在评估疾病状态（复发和缓解）之间脂质谱的差异。为此，我们使用亲水相互作用液相色谱-质谱联用技术对多发性硬化症患者的血清样本进行了磷脂组学分析。我们的研究结果表明，多发性硬化症具有不同于健康对照组的磷脂组学特征，特别是 PE、PC、LPE、醚键连接的 PE 和醚键连接的 PC 种类。天然内源性抗氧化剂如 PC 和 PE 溶血磷脂酰胆碱以及 PC 和 PE 多不饱和脂肪酸酯化物种在多发性硬化症患者和多发性硬化症缓解和复发患者中水平显著降低。我们的研究结果首次表明，多发性硬化症患者的血清磷脂组学与健康对照组明显不同，少数磷脂，如 PC(34:3)、PC(36:6)、PE(40:10)和 PC(38:1)，其最低 p 值，可能适合作为多发性硬化症临床应用的生物标志物。
