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Blood metabolomic and transcriptomic signatures stratify patient subgroups in multiple sclerosis according to disease severity

Oppong, Alexandra E; Coelewij, Leda; Robertson, Georgia; Martin-Gutierrez, Lucia; Waddington, Kirsty E; Dönnes, Pierre; Nytrova, Petra; ... Jury, Elizabeth C; + view all (2024) Blood metabolomic and transcriptomic signatures stratify patient subgroups in multiple sclerosis according to disease severity. iScience , 27 (3) , Article 109225. 10.1016/j.isci.2024.109225. Green open access

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Abstract

There are no blood-based biomarkers distinguishing patients with relapsing-remitting (RRMS) from secondary progressive multiple sclerosis (SPMS) although evidence supports metabolomic changes according to MS disease severity. Here machine learning analysis of serum metabolomic data stratified patients with RRMS from SPMS with high accuracy and a putative score was developed that stratified MS patient subsets. The top differentially expressed metabolites between SPMS versus patients with RRMS included lipids and fatty acids, metabolites enriched in pathways related to cellular respiration, notably, elevated lactate and glutamine (gluconeogenesis-related) and acetoacetate and bOHbutyrate (ketone bodies), and reduced alanine and pyruvate (glycolysis-related). Serum metabolomic changes were recapitulated in the whole blood transcriptome, whereby differentially expressed genes were also enriched in cellular respiration pathways in patients with SPMS. The final gene-metabolite interaction network demonstrated a potential metabolic shift from glycolysis toward increased gluconeogenesis and ketogenesis in SPMS, indicating metabolic stress which may trigger stress response pathways and subsequent neurodegeneration.

Type: Article
Title: Blood metabolomic and transcriptomic signatures stratify patient subgroups in multiple sclerosis according to disease severity
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.isci.2024.109225
Publisher version: https://doi.org/10.1016/j.isci.2024.109225
Language: English
Additional information: © 2024 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation
URI: https://discovery.ucl.ac.uk/id/eprint/10188290
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