Lipid profile of cerebrospinal fluid in multiple sclerosis patients: a potential tool for diagnosis

Nogueras, Lara; Gonzalo, H.; Jové, Mariona; Sol, Joaquím; Gil-Sánchez, Anna; Hervás, José Vicente; Valcheva, Petya; González-Mingot, Cristina; Solana, María José; Peralta, Sílvia; Pamplona, Reinald; Brieva, Luís

doi:10.1038/s41598-019-47906-x

Cited by 47 publications

(34 citation statements)

References 42 publications

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“…There are only a few reports in the literature that analysed CSF lipids in MS or GBS. These studies were targeted either on SM analysis in demyelinating disorders of the PNS 26 , on the assessment of the sphingolipidome 27 or the global lipidome with a fatty acid-targeted approach 28 in patients with MS, or on the polar metabolome from patients with MS 29 and GBS 30 .…”

Section: Discussionmentioning

confidence: 99%

Cerebrospinal fluid lipidomic biomarker signatures of demyelination for multiple sclerosis and Guillain–Barré syndrome

Péter

Török

Petrovics-Balog

et al. 2020

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Multiple sclerosis (MS) and Guillain–Barré syndrome (GBS) are demyelinating disorders affecting the central nervous system and peripheral nervous system (PNS), respectively. Cerebrospinal fluid (CSF) is one of the most valuable sources of diagnostic biomarkers in neurological diseases. In the present study high sensitivity shotgun mass spectrometry was used to characterise the CSF lipidome of patients with MS, GBS and controls with non-demyelinating diseases. The quantification of 222 CSF lipid molecular species revealed characteristic changes in the absolute and relative lipid concentrations in MS and GBS compared to the controls. For the GBS group, the fourfold elevation in the total lipid content was a discriminatory and a newly identified feature of PNS demyelination. In contrast, in MS, the accumulation of the myelin-derived cerebrosides represented a specific feature of demyelination. As a common feature of demyelination, we identified upregulated levels of lipid metabolic intermediates. We found strong positive correlation between total protein content and lipid concentrations in both diseases. By exploring the CSF lipidome we demonstrate usefulness of broad-range shotgun lipidomic analysis as a fast and reliable method of biomarker discovery in patients with demyelinating neurological disorders that might be a valuable diagnostic complement to existing examinations.

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Section: Discussionmentioning

confidence: 99%

Cerebrospinal fluid lipidomic biomarker signatures of demyelination for multiple sclerosis and Guillain–Barré syndrome

Péter

Török

Petrovics-Balog

et al. 2020

Sci Rep

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“…An increasing number of studies have shown that, oxidative stress (OS) — defined as the homeostatic imbalance between the production of free radicals and their neutralization by antioxidant defenses (Salim, 2017) – plays an important role in the pathogenesis of MS (Ridet et al, 1997; Gilgun-Sherki et al, 2004; Sospedra and Martin, 2005; Miljković and Spasojević, 2013; Ohl et al, 2016). So far, OS has been shown to be involved in different MS processes such as: (i) in the activation of immune cells, especially T cells (Corthay, 2006); (ii) in the loss of blood – brain barrier (BBB) selectivity (Wu and Tsirka, 2009), (iii) facilitating T-cell migration and infiltration into the CNS (Marui et al, 1993), (iv) increasing the expression of the cytokine network (Kroenke et al, 2008; Jäger et al, 2009), (vi) in MS tissue spread, especially mediated by lipooxidation processes (Gonzalo et al, 2012; Nogueras et al, 2019); and (vii) promoting changes in the clinical evolution of the disease (Fiorini et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Impairment of Mitochondrial Redox Status in Peripheral Lymphocytes of Multiple Sclerosis Patients

et al. 2019

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Literature suggests that oxidative stress (OS) may be involved in the pathogenesis of multiple sclerosis (MS), in which the immune system is known to play a key role. However, to date, the OS in peripheral lymphocytes and its contribution to the disease remain unknown. The aim of the present study was to explore the influence of OS in peripheral lymphocytes of MS patients. To that end, a cross-sectional, observational pilot study was conducted [n = 58: 34 MS and 24 healthy subjects (control group)]. We have measured superoxide production and protein mitochondrial complex levels in peripheral blood mononuclear cells (PBMCs) isolated from MS patients and control. Lactate levels and the antioxidant capacity were determined in plasma. We adjusted the comparisons between study groups by age, sex and cell count according to case. Results demonstrated that PBMCs, specifically T cells, from MS patients exhibited significantly increased superoxide anion production compared to control group (p = 0.027 and p = 0.041, respectively). Increased superoxide production in PBMCs was maintained after the adjustment (p = 0.044). Regarding mitochondrial proteins, we observe a significant decrease in the representative protein content of the mitochondrial respiratory chain complexes I-V in PBMCs of MS patients (p = 0.002, p = 0.037, p = 0.03, p = 0.044, and p = 0.051, respectively), which was maintained for complexes I, III, and V after the adjustment (p = 0.026; p = 0.033; p = 0.033, respectively). In MS patients, a trend toward increased plasma lactate concentration was detected [8.04 mg lactate/dL (5.25, 9.49) in the control group, 11.36 mg lactate/dL (5.41, 14.81) in MS patients] that was statistically significant after the adjustment (p = 0.013). This might be indicative of compromised mitochondrial function. Finally, antioxidant capacity was also decreased in plasma from MS patients, both before (p = 0.027) and after adjusting for sex and age (p = 0.006). Our findings demonstrate that PBMCs of MS patients show impaired mitochondrial redox status and deficient antioxidant capacity. These results demonstrate for the first time the existence of mitochondrial alterations in the cells immune cells of MS patients already at the peripheral level.

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“…a powerful tool to identify molecules associated with pathological conditions, which may lead to the discovery of new therapeutic targets. Previous studies, mostly focused on RRMS, have reported differential lipids in the CSF and serum of MS patients compared with healthy individuals [2][3][4][5][6] . However, still very little is known about the lipid signals affecting the temporal progression of the disease course and this was the aim of our exploratory study.…”

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confidence: 99%

Retrospective unbiased plasma lipidomic of progressive multiple sclerosis patients-identifies lipids discriminating those with faster clinical deterioration

Amatruda

Petracca

Wentling

et al. 2020

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The disease course of patients with a confirmed diagnosis of primary progressive multiple sclerosis (PPMS) is uncertain. In an attempt to identify potential signaling pathways involved in the evolution of the disease, we conducted an exploratory unbiased lipidomic analysis of plasma from non-diseased controls (n = 8) and patients with primary progressive MS (PPMS, n = 19) and either a rapid (PPMS-P, n = 9) or slow (PPMS-NP, n = 10) disease course based on worsening disability and/or MRI-visible appearance of new T2 lesions over a one-year-assessment. Partial least squares-discriminant analysis of the MS/MSALL lipidomic dataset, identified lipids driving the clustering of the groups. Among these lipids, sphingomyelin-d18:1/14:0 and mono-hexosylceramide-d18:1/20:0 were differentially abundant in the plasma of PPMS patients compared to controls and their levels correlated with MRI signs of disease progression. Lyso-phosphatidic acid-18:2 (LPA-18:2) was the only lipid with significantly lower abundance in PPMS patients with a rapidly deteriorating disease course, and its levels inversely correlated with the severity of the neurological deficit. Decreased levels of LPA-18:2 were detected in patients with more rapid disease progression, regardless of therapy and these findings were validated in an independent cohort of secondary progressive (SPMS) patients, but not in a third cohorts of relapsing–remitting (RRMS) patients. Collectively, our analysis suggests that sphingomyelin-d18:1/14:0, mono-hexosylceramide-d18:1/20:0, and LPA-18:2 may represent important targets for future studies aimed at understanding disease progression in MS.

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Lipid profile of cerebrospinal fluid in multiple sclerosis patients: a potential tool for diagnosis

Cited by 47 publications

References 42 publications

Cerebrospinal fluid lipidomic biomarker signatures of demyelination for multiple sclerosis and Guillain–Barré syndrome

Cerebrospinal fluid lipidomic biomarker signatures of demyelination for multiple sclerosis and Guillain–Barré syndrome

Impairment of Mitochondrial Redox Status in Peripheral Lymphocytes of Multiple Sclerosis Patients

Retrospective unbiased plasma lipidomic of progressive multiple sclerosis patients-identifies lipids discriminating those with faster clinical deterioration

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