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

Abstract

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.

New Insights into Multiple Sclerosis Mechanisms: Lipids on the Track to Control Inflammation and Neurodegeneration

“…These findings are consistent with the previous ones that reported altered levels of glycerolipids in plasma of PPMS patients [134] as well as glycerolipids and PLs in CSF of MS patients [135,136]. Amatruda et al employed lipidomic analysis of plasma of PPMS to identify lipids related with faster clinical deterioration [137]. They found a significantly increased level of C20:0-HexCer and decreased levels of C14:0-SM and C18:2-lysophospatidic acid (LPA) in those with rapid progression.…”

“…Amatruda et al employed lipidomic analysis of plasma of PPMS to identify lipids related with faster clinical deterioration [ 137 ]. They found a significantly increased level of C20:0-HexCer and decreased levels of C14:0-SM and C18:2-lysophospatidic acid (LPA) in those with rapid progression.…”

“…Furthermore, altered level of lysoPC in MS CSF was associated with altered plasma levels of lysoPC, lysoPE, hydrocortisone, and oxidized fatty acids; the changes related to rate of relapses or increase in disability over time [ 159 ]. Plasma levels of C20:0-HexCer were increased, while C18:2-LPA decreased in the subjects with progressive MS, with the latter showing inverse correlation with rate of deterioration in neurological deficit [ 137 ]. In RRMS patients, a smaller increase in plasma level of HDL cholesterol (HDL-C) during 5 years of follow-up was observed for those who converted to SPMS within this period [ 158 ].…”

“…Serum levels of 24(S)-OHC negatively correlated to normalized brain volume measurements in magnetic resonance image (MRI) of RRMS patients [ 157 ]. Levels of C20:0-HexCer showed correlation with indices of global brain atrophy at the one-year follow-up in patients with primary progressive type of MS [ 137 ]. During 5 years of follow-up, a positive correlation was observed between increase in LDL cholesterol (LDL-C) plasma levels and occurrence of new T2 lesions, while increase in HDL-C inversely correlated with rate of cerebral gray matter atrophy in MRI, both for relapsing–remitting and progressive MS [ 158 ].…”

Eating Hubs in Multiple Sclerosis: Exploring the Relationship Between Mediterranean Diet and Disability Status in Italy

“…Indeed, a previous study has shown that patients, following an initial clinical diagnosis of CNS demyelination, tend to change their diet, increasing the amount of fruit and/or vegetables and following a low-fat diet ( 35 ). Additionally, a recent work has shown a trend toward reduced levels of storage lipids (fatty acids, cholesterol esters, triglycerides, and diglycerides) in the plasma of PwMS in comparison with HC ( 36 ). Additionally, in line with previous findings highlighting the potential effects of MeDi on MS course and disability ( 16 ) in our study participants higher consumption of vegetables and fish was inversely correlated to global motor disability, as assessed via EDSS.…”