Abstract
The lack of a single predictive or diagnostic test in multiple sclerosis (MS) remains a major obstacle in the patient’s care. The aim of this study was to investigate metabolic profiles, especially lipids in cerebrospinal fluid (CSF) using 1H-NMR spectroscopy and metabolomics analysis to discriminate MS patient group from the control ones. In this study, 19 MS patients and 19 controls, without neurological problems, patients were enrolled. To obtain the CSF metabolic profiles, NMR spectroscopy was used. Hydrophilic and hydrophobic compounds were analyzed using univariate and multivariate supervised analysis orthogonal partial least square discriminant analysis (OPLS-DA). Targeted OPLS-DA analysis of 32 hydrophilic and 17 hydrophobic compounds obtained 9 hydrophilic metabolites and 8 lipid functional groups which had the highest contribution to patient’s group separation. Lower concentrations of CSF hydrophilic and hydrophobic compounds were observed in MS patients as compared to control group. Acetone, choline, urea, 1,3-dimethylurate, creatinine, isoleucine, myo-inositol, leucine, and 3-OH butyrate; saturated and monounsaturated acyl groups of ω–9, ω–7, ω–6, ω–3, and fatty acid, triglycerides, 1,3-DG, 1-MG, and unassigned component signal at 3.33 ppm were the most important signal compounds in group separation. Analysis of metabolic profile of raw CSF and their lipid extract shows decreased levels of many compounds and led to the conclusion that MS patients could have a disturbance in many metabolic pathways perhaps leading to the decreased level of acetyl-CoA and/or inflammation. CSF metabolic profile analyses could be used as a fingerprint for early MS diagnosis.
Highlights
Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system (CNS) characterized by demyelination and simultaneous axonal and neuronal degeneration that occurs from the earliest clinical stage of the disease (Campbell et al 2011)
The most important parameters (VIP > 1) that contributed to class separation were the Nuclear magnetic resonance (NMR) signals from acetone, choline, urea, 1,3-dimethylurate, creatinine, isoleucine, myo-inositol, leucine, and 3-OH-butyrate
The most important parameters (VIP > 1) that contributed to class separation were the signals from –CH3– saturated, monounsaturated ω–9 and/ or ω–7 acyl groups and fatty acid (FA) (0.86 ppm), –CH3
Summary
Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system (CNS) characterized by demyelination and simultaneous axonal and neuronal degeneration that occurs from the earliest clinical stage of the disease (Campbell et al 2011). At the places of damaged axons and oligodendrocytes, the changes in the inflammation occur which cause the formation of active and inactive demyelinating plaques in the brain (Brosnan et al 1996). In 90% of patients with MS, local disturbances of B cells’ response elicit presence of oligoclonal bands in CSF which have been proposed as a helpful biomarker for MS diagnosis and evaluation of treatment. Their presence discloses the intrathecal immunoglobulin G (IgG) synthesis (Bo et al 1994). There have been advances in molecular biology, cellular immunology, and Bomics^ (genomics, proteomics, metabolomics) which focus on exploring the processes underlying disease pathogenesis to provide a list of possible MS biomarkers (Kuhle et al 2015; Poddighe et al 2017)
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