Distinct plasma lipids predict axonal injury and multiple sclerosis activity.

Area of Science:

• Neuroscience
• Biochemistry
• Immunology

Background:

• Lipids are crucial in neuroinflammation and neuroinjury due to their role in myelin structure and immune modulation.
• Understanding lipid profiles can offer insights into disease mechanisms and progression.

Purpose of the Study:

• To conduct an in-depth lipidomics analysis in pediatric-onset multiple sclerosis (MS).
• To identify specific lipids associated with neuroinjury markers and disease activity.

Main Methods:

• Plasma samples from 435 pediatric MS patients within 4 years of onset were analyzed using untargeted and targeted mass spectrometry.
• Machine learning models predicted neurofilament light chain (NfL) levels cross-sectionally.
• Longitudinal analyses assessed associations between lipid metabolites and clinical/imaging outcomes.

Main Results:

• Structural lipids (phosphatidylcholines, phosphatidylethanolamines) were strong predictors of NfL levels.
• Polyunsaturated fatty acids (PUFAs) and their derivatives demonstrated a protective association with subsequent disease activity (relapses, MRI lesions).

Conclusions:

• Two lipid categories are linked to MS: structural lipids associated with cell lysis and NfL, and PUFAs, particularly omega-3, exhibiting a protective role.
• Lipidomics can differentiate between injury-related lipids and those with potential therapeutic benefits in MS.