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Lipidomic UPLC-MS/MS Profiles of Normal-Appearing White Matter Differentiate Primary and Secondary Progressive Multiple Sclerosis

1
Biomolecular Sciences Research Centre, Faculty of Health, Wellbeing and Life Sciences, Sheffield Hallam University, Sheffield S1 1WB, UK
2
Leicester School of Allied Health Sciences, Faculty of Health and Life Science, De Montfort University Leicester, Leicester LE1 9BH, UK
*
Author to whom correspondence should be addressed.
Current Address: Department of Chemistry, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
Metabolites 2020, 10(9), 366; https://doi.org/10.3390/metabo10090366
Received: 28 August 2020 / Accepted: 7 September 2020 / Published: 8 September 2020
Multiple sclerosis (MS) is a neurodegenerative inflammatory disease where an autoimmune response to components of the central nervous system leads to a loss of myelin and subsequent neurological deterioration. People with MS can develop primary or secondary progressive disease (PPMS, SPMS) and differentiation of the specific differences in the pathogenesis of these two courses, at the molecular level, is currently unclear. Recently, lipidomics studies using human biofluids, mainly plasma and cerebrospinal fluid, have highlighted a possible role for lipids in the initiation and progression of MS. However, there is a lack of lipidomics studies in MS on CNS tissues, such as normal-appearing white matter (NAWM), where local inflammation initially occurs. Herein, we developed an untargeted reverse phase ultra-performance liquid chromatography time of flight tandem mass spectrometry (RP-UPLC-TOF MSE)-based workflow, in combination with multivariate and univariate statistical analysis, to assess significant differences in lipid profiles in brain NAWM from post-mortem cases of PPMS, SPMS and controls. Groups of eight control, nine PPMS and seven SPMS NAWM samples were used. Correlation analysis of the identified lipids by RP-UPLC-TOF MSE was undertaken to remove those lipids that correlated with age, gender and post-mortem interval as confounding factors. We demonstrate that there is a significantly altered lipid profile of control cases compared with MS cases and that progressive disease, PPMS and SPMS, can be differentiated on the basis of the lipidome of NAWM with good sensitivity, specificity and prediction accuracy based on receiver operating characteristic (ROC) curve analysis. Metabolic pathway analysis revealed that the most altered lipid pathways between PPMS and SPMS were glycerophospholipid metabolism, glycerophosphatidyl inositol (GPI) anchor synthesis and linoleic acid metabolism. Further understanding of the impact of these lipid alterations described herein associated with progression will provide an increased understanding of the mechanisms underpinning progression and highlight possible new therapeutic targets. View Full-Text
Keywords: multiple sclerosis; progression; lipidomics; neurodegeneration; glycerophospholipids multiple sclerosis; progression; lipidomics; neurodegeneration; glycerophospholipids
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MDPI and ACS Style

Pousinis, P.; Ramos, I.R.; Woodroofe, M.N.; Cole, L.M. Lipidomic UPLC-MS/MS Profiles of Normal-Appearing White Matter Differentiate Primary and Secondary Progressive Multiple Sclerosis. Metabolites 2020, 10, 366. https://doi.org/10.3390/metabo10090366

AMA Style

Pousinis P, Ramos IR, Woodroofe MN, Cole LM. Lipidomic UPLC-MS/MS Profiles of Normal-Appearing White Matter Differentiate Primary and Secondary Progressive Multiple Sclerosis. Metabolites. 2020; 10(9):366. https://doi.org/10.3390/metabo10090366

Chicago/Turabian Style

Pousinis, Petros, Ines R. Ramos, M. N. Woodroofe, and Laura M. Cole 2020. "Lipidomic UPLC-MS/MS Profiles of Normal-Appearing White Matter Differentiate Primary and Secondary Progressive Multiple Sclerosis" Metabolites 10, no. 9: 366. https://doi.org/10.3390/metabo10090366

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