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Biochemical Differences in Cerebrospinal Fluid between Secondary Progressive and Relapsing-Remitting Multiple Sclerosis
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Uppsala University, Science for Life Laboratory, SciLifeLab. (Spjuth group)ORCID iD: 0000-0001-9382-3273
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.ORCID iD: 0000-0003-0214-596X
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Uppsala University, Science for Life Laboratory, SciLifeLab.ORCID iD: 0000-0002-8083-2864
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.ORCID iD: 0000-0002-7045-1806
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2019 (English)In: Cells, ISSN 2073-4409, Vol. 8, no 2, article id 84Article in journal (Refereed) Published
Abstract [en]

To better understand the pathophysiological differences between secondary progressive multiple sclerosis (SPMS) and relapsing-remitting multiple sclerosis (RRMS), and to identify potential biomarkers of disease progression, we applied high-resolution mass spectrometry (HRMS) to investigate the metabolome of cerebrospinal fluid (CSF). The biochemical differences were determined using partial least squares discriminant analysis (PLS-DA) and connected to biochemical pathways as well as associated to clinical and radiological measures. Tryptophan metabolism was significantly altered, with perturbed levels of kynurenate, 5-hydroxytryptophan, 5-hydroxyindoleacetate, and N-acetylserotonin in SPMS patients compared with RRMS and controls. SPMS patients had altered kynurenine compared with RRMS patients, and altered indole-3-acetate compared with controls. Regarding the pyrimidine metabolism, SPMS patients had altered levels of uridine and deoxyuridine compared with RRMS and controls, and altered thymine and glutamine compared with RRMS patients. Metabolites from the pyrimidine metabolism were significantly associated with disability, disease activity and brain atrophy, making them of particular interest for understanding the disease mechanisms and as markers of disease progression. Overall, these findings are of importance for the characterization of the molecular pathogenesis of SPMS and support the hypothesis that the CSF metabolome may be used to explore changes that occur in the transition between the RRMS and SPMS pathologies.

Place, publisher, year, edition, pages
2019. Vol. 8, no 2, article id 84
Keywords [en]
cerebrospinal fluid, mass spectrometry, metabolomics, multiple sclerosis, pyrimidine, tryptophan
National Category
Clinical Medicine
Identifiers
URN: urn:nbn:se:uu:diva-375564DOI: 10.3390/cells8020084ISI: 000460896000006PubMedID: 30678351OAI: oai:DiVA.org:uu-375564DiVA, id: diva2:1284187
Funder
Åke Wiberg FoundationEU, Horizon 2020, 654241Available from: 2019-01-31 Created: 2019-01-31 Last updated: 2019-04-11Bibliographically approved

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Herman, StephanieÅkerfeldt, TorbjörnSpjuth, OlaBurman, JoachimKultima, Kim

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