Missailidis et al. (2026)
- Authors: Daniel Missailidis, Christopher W. Armstrong, Dovile Anderson, Claire Y. Allan, Oana Sanislav, Paige K. Smith, Tammy Esmaili, Darren J. Creek, Sarah J. Annesley, Paul R. Fisher
- Institutes: Department of Biochemistry and Pharmacology, The University of Melbourne, Melbourne, Australia, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Australia, Department of Microbiology, Anatomy, Physiology and Pharmacology, La Trobe University, Melbourne, Australia
- Publisher: Journal of Translational Medicine
- Link: DOI
Summary
This study identifies a distinct metabolic signature in ME/CFS immune cells, characterized by a significant accumulation of lipids and a shift toward saturated fats. By integrating multiple biological datasets, the researchers pinpointed specific lipid biomarkers and enzyme dysfunctions that could explain the impaired energy production and immune signaling seen in patients. These findings offer a potential path for developing objective diagnostic tests and exploring metabolic therapies to restore cellular health.
What was researched?
The study investigated the polar metabolomes and non-polar lipidomes of immune cell lines to identify metabolic abnormalities and potential biomarkers for ME/CFS.
Why was it researched?
Researchers sought to expand on previous evidence suggesting that lymphoid cells in ME/CFS patients undergo a metabolic shift characterized by an increased demand for lipids for energy production.
How was it researched?
This was a case-control study using lymphoblastoid cell lines (LCLs) derived from 15 female ME/CFS patients and 17 healthy controls. The team employed a multi-omics approach, integrating new metabolomic and lipidomic data with existing proteomic and transcriptomic profiles using advanced bioinformatics tools.
What has been found?
The researchers discovered that ME/CFS cell lines show a significant accumulation of lipids, including triglycerides and fatty acids, with a shift toward more saturated lipid content. A specific lipid, PC(O-38:4), was found to be significantly reduced and acted as a near-perfect discriminator between patients and controls. Additionally, the study confirmed the elevated activity of the enzyme PTDSS1 and identified 15 dysregulated metabolic pathways.
Discussion
The findings suggest that excess lipids may disrupt ‘lipid rafts’ and cell membrane fluidity, potentially impairing B-cell receptor signaling. Limitations include the use of immortalized cell lines rather than fresh primary cells, a small all-female sample size, and the lack of control for body mass index (BMI).
Conclusion & Future Work
ME/CFS is associated with profound cellular lipid dysregulation and altered enzyme activity in B-cell-derived lines. Future research should focus on validating these lipid abnormalities in primary immune cells to further dissect the immunometabolic mechanisms of the disease.