CSF sphingolipids are correlated with neuroinflammatory cytokines and differentiate neuromyelitis optica spectrum disorder from multiple sclerosis.

Autor:	Shi L; School of Medical Sciences, Charles Perkins Centre, and Brain and Mind Centre, The University of Sydney, Sydney, New South Wales, Australia., Ghezzi L; Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.; La Fondazione IRCCS Ospedale Maggiore Policlinico, Milano, Italy., Fenoglio C; Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.; La Fondazione IRCCS Ospedale Maggiore Policlinico, Milano, Italy., Pietroboni AM; La Fondazione IRCCS Ospedale Maggiore Policlinico, Milano, Italy., Galimberti D; Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.; La Fondazione IRCCS Ospedale Maggiore Policlinico, Milano, Italy., Pace F; Department of Neurology, Washington University in St Louis, St Louis, Missouri, USA.; Department of Clinical-Surgical Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Lombardia, Italy., Hardy TA; Concord Hospital, Department of Neurology, The University of Sydney, Sydney, New South Wales, Australia., Piccio L; School of Medical Sciences, Charles Perkins Centre, and Brain and Mind Centre, The University of Sydney, Sydney, New South Wales, Australia anthony.don@sydney.edu.au laura.piccio@sydney.edu.au.; Department of Neurology, Washington University in St Louis, St Louis, Missouri, USA., Don AS; School of Medical Sciences, Charles Perkins Centre, and Brain and Mind Centre, The University of Sydney, Sydney, New South Wales, Australia anthony.don@sydney.edu.au laura.piccio@sydney.edu.au.
Jazyk:	angličtina
Zdroj:	Journal of neurology, neurosurgery, and psychiatry [J Neurol Neurosurg Psychiatry] 2024 Dec 16; Vol. 96 (1), pp. 54-67. Date of Electronic Publication: 2024 Dec 16.
DOI:	10.1136/jnnp-2024-333774
Abstrakt:	Background: There is a need for biomarkers of disease progression and therapeutic response in multiple sclerosis (MS). This study aimed to identify cerebrospinal fluid (CSF) lipids that differentiate MS from other neuroinflammatory conditions and correlate with Expanded Disability Status Scale (EDSS) scores, gadolinium-enhancing lesions or inflammatory mediators. Methods: Lipids and inflammatory cytokines/chemokines were quantified with liquid chromatography-tandem mass spectrometry and multiplex ELISA, respectively, in CSF from people with untreated MS, neuromyelitis optica spectrum disorder (NMOSD), other inflammatory neurological diseases and non-inflammatory neurological diseases (NIND). Analytes were compared between groups using analysis of variance, and correlations were assessed with Pearson's analysis. Results: Twenty-five sphingolipids and four lysophosphatidylcholines were significantly higher in NMOSD compared with MS and NIND cases, whereas no lipids differed significantly between MS and NIND. A combination of three sphingolipids differentiated NMOSD from MS with the area under the curve of 0.92 in random forest models. Ninety-four lipids, including those that differentiated NMOSD from MS, were positively correlated with macrophage migration inhibitory factor (MIF) and 37 lipids were positively correlated with CSF protein in two independent MS cohorts. EDSS was inversely correlated with cholesterol ester CE(16:0) in both MS cohorts. In contrast, MIF and soluble triggering receptor expressed on myeloid cells 2 were positively associated with EDSS. Conclusions: CSF sphingolipids are positively correlated with markers of neuroinflammation and differentiate NMOSD from MS. The inverse correlation between EDSS and CE(16:0) levels may reflect poor clearance of cholesterol released during myelin break-down and warrants further investigation as a biomarker of therapeutic response. Competing Interests: Competing interests: TAH has received honoraria for talks, advisory boards or support for scientific meetings from Bayer-Schering, Biogen Idec, Novartis, Teva, Merck, Alexion, Briston Myers Squibb and Sanofi-Genzyme, and is a paid writer for Australian MS Research Review. (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY. Published by BMJ Group.)
Databáze:	MEDLINE
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