The Serum Lipid Profile of Relapsing Multiple Sclerosis Differs Reproducibly From Healthy Controls

Area of Science:

• Neuroimmunology
• Biochemistry
• Clinical Diagnostics

Background:

• Multiple sclerosis (MS) diagnosis and monitoring require reliable biomarkers for inflammation and neurodegeneration.
• Serum lipid profiles are largely unexplored as potential MS biomarkers.

Purpose of the Study:

• To identify serum lipids that are consistently altered in relapsing-remitting multiple sclerosis (RRMS).
• To correlate these lipid alterations with indicators of MS disease severity.

Main Methods:

• Serum lipid quantification using liquid chromatography-tandem mass spectrometry in discovery and validation cohorts.
• Statistical analysis including ANOVA and random forest modeling to compare lipid levels and predict RRMS.
• Correlation analysis with clinical measures such as Expanded Disability Severity Scale (EDSS) and Multiple Sclerosis Severity Scale (MSSS).

Main Results:

• Twenty-five specific lipids, including lysophosphatidylcholines (LPC), lysophosphatidylethanolamines (LPE), and sphingomyelins (SM), were significantly elevated in RRMS patients compared to controls.
• Random forest models demonstrated high accuracy in predicting RRMS based on lipid profiles.
• Certain acylcarnitines and ceramides correlated with EDSS scores in the validation cohort, and a neuron-enriched sphingomyelin (SM) was higher during relapse.

Conclusions:

• A distinct panel of 25 serum lipids is reproducibly elevated in RRMS patients.
• Elevated lipids may represent peripheral lipolysis and neurodegeneration, suggesting potential as novel MS biomarkers.
• Further research is warranted to explore the predictive value of these serum lipids for brain atrophy and disease progression.