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Biochemical Differences in Cerebrospinal Fluid between Secondary Progressive and Relapsing–Remitting Multiple Sclerosis

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 metab...

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Autores principales: Herman, Stephanie, Åkerfeldt, Torbjörn, Spjuth, Ola, Burman, Joachim, Kultima, Kim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6406712/
https://www.ncbi.nlm.nih.gov/pubmed/30678351
http://dx.doi.org/10.3390/cells8020084
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author Herman, Stephanie
Åkerfeldt, Torbjörn
Spjuth, Ola
Burman, Joachim
Kultima, Kim
author_facet Herman, Stephanie
Åkerfeldt, Torbjörn
Spjuth, Ola
Burman, Joachim
Kultima, Kim
author_sort Herman, Stephanie
collection PubMed
description 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.
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spelling pubmed-64067122019-03-19 Biochemical Differences in Cerebrospinal Fluid between Secondary Progressive and Relapsing–Remitting Multiple Sclerosis Herman, Stephanie Åkerfeldt, Torbjörn Spjuth, Ola Burman, Joachim Kultima, Kim Cells Article 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. MDPI 2019-01-24 /pmc/articles/PMC6406712/ /pubmed/30678351 http://dx.doi.org/10.3390/cells8020084 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Herman, Stephanie
Åkerfeldt, Torbjörn
Spjuth, Ola
Burman, Joachim
Kultima, Kim
Biochemical Differences in Cerebrospinal Fluid between Secondary Progressive and Relapsing–Remitting Multiple Sclerosis
title Biochemical Differences in Cerebrospinal Fluid between Secondary Progressive and Relapsing–Remitting Multiple Sclerosis
title_full Biochemical Differences in Cerebrospinal Fluid between Secondary Progressive and Relapsing–Remitting Multiple Sclerosis
title_fullStr Biochemical Differences in Cerebrospinal Fluid between Secondary Progressive and Relapsing–Remitting Multiple Sclerosis
title_full_unstemmed Biochemical Differences in Cerebrospinal Fluid between Secondary Progressive and Relapsing–Remitting Multiple Sclerosis
title_short Biochemical Differences in Cerebrospinal Fluid between Secondary Progressive and Relapsing–Remitting Multiple Sclerosis
title_sort biochemical differences in cerebrospinal fluid between secondary progressive and relapsing–remitting multiple sclerosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6406712/
https://www.ncbi.nlm.nih.gov/pubmed/30678351
http://dx.doi.org/10.3390/cells8020084
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