Multi-omics identifies lipid accumulation in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome cell lines: a case-control study.
Missailidis, Daniel, Armstrong, Christopher W, Anderson, Dovile et al. · Journal of translational medicine · 2026 · DOI
Quick Summary
Researchers studied immune cells from people with ME/CFS and found that these cells accumulate abnormal amounts of fats (lipids) compared to healthy controls. The cells also show changes in how they process and use these fats for energy. This discovery suggests that problems with how the body handles fats might be part of what makes ME/CFS different at the cellular level.
Why It Matters
Understanding lipid metabolism abnormalities in ME/CFS cells provides new mechanistic insight into disease pathophysiology and identifies potential therapeutic targets. This work bridges cellular metabolism with immune dysfunction, which could guide future studies investigating how metabolic changes affect immune cell function in ME/CFS.
Observed Findings
Triglycerides, diradylglycerolipids, and fatty acids were significantly elevated in ME/CFS cell lines compared to controls.
PC(O-38:4) lipid levels were substantially reduced in ME/CFS cells and were almost entirely discriminative of disease status.
ME/CFS cells showed significantly higher saturated lipid content overall compared to healthy control cells.
Expression of phosphatidylserine synthase 1 (PTDSS1) and 7 other lipid metabolism-related gene products were concordantly elevated in ME/CFS cells across transcriptomic and proteomic datasets.
No significantly altered individual features were detected in the polar metabolome analysis.
Inferred Conclusions
B cells from people with ME/CFS exhibit lipid accumulation and dysregulated lipid metabolism pathways that are distinguishable from healthy controls.
Altered activity of lipid-synthesis and lipid-remodeling enzymes, particularly PTDSS1, may drive the observed lipid abnormalities in ME/CFS.
Lipid metabolic dysfunction may contribute to immune cell dysfunction in ME/CFS through altered cell membrane composition and energy metabolism.
Remaining Questions
Do these lipid abnormalities occur in primary circulating B cells and other immune cells from ME/CFS patients, or are they specific to immortalized cell lines?
What This Study Does Not Prove
This study does not prove that lipid accumulation causes ME/CFS symptoms or definitively establishes whether these metabolic changes occur in primary immune cells in patient blood. The findings are correlational and derived from immortalized cell lines, which may not fully represent the complex biology of living tissue and may not directly translate to therapeutic interventions.
What is the functional consequence of lipid accumulation and altered saturation profiles on immune cell effector functions such as cytokine production, antibody secretion, or antigen presentation?
Are lipid metabolism abnormalities reversible, and could targeting PTDSS1 or related enzymes ameliorate immune dysfunction in ME/CFS?
Do these metabolic changes differ between ME/CFS patients of different sexes, disease severity levels, or disease duration?