Hoel et al. (2026)
- Authors: August Hoel, Fredrik Hoel, Sissel Elisabeth Furesund Dyrstad, Henrique Chapola, Ingrid Gurvin Rekeland, Kristin Risa, Kine Alme, Kari Sørland, Karl Albert Brokstad, Hans-Peter Marti, Olav Mella, Øystein Fluge, Karl Johan Tronstad
- Institutes: Department of Biomedicine, University of Bergen, Bergen, Norway, Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway, Department of Safety, Chemistry and Biomedical Laboratory Sciences, Western Norway University of Applied Sciences, Bergen, Norway
- Publisher: Cell Reports Medicine
- Link: DOI
Summary
This landmark study identifies a distinct molecular ‘fingerprint’ in the blood of ME/CFS patients, characterized by an overabundance of immune-related signaling proteins and a deficit in essential muscle and cellular proteins. These findings suggest the disease involves a systemic state of immune reprogramming and metabolic stress, providing a concrete biological basis for symptoms like muscle fatigue and post-exertional malaise. By mapping thousands of proteins, the researchers have created a foundation for developing accurate diagnostic tests and targeted therapies that could finally address the underlying biology of the condition.
What was researched?
The study aimed to map the comprehensive profile of proteins circulating in the blood of ME/CFS patients to identify biological markers and clarify the underlying disease mechanisms.
Why was it researched?
ME/CFS lacks established diagnostic biomarkers and clear clinical treatments, necessitating large-scale molecular studies to understand how the disease affects different organ systems and biological processes.
How was it researched?
Researchers used advanced aptamer-based technology to analyze 7,326 protein targets in the serum of 50 ME/CFS patients and 29 healthy controls. They validated their primary findings using independent antibody-based testing methods and performed cross-system profiling to link protein changes to specific tissues and biological pathways.
What has been found?
The analysis identified 845 proteins with significantly altered levels in ME/CFS patients, revealing a broad increase in secreted proteins related to inflammation, coagulation, and immune signaling. Conversely, there was a notable reduction in intracellular proteins, particularly those originating from skeletal muscle and activated neutrophils. These patterns indicate a state of systemic immune reprogramming and metabolic disturbances that are consistent across different patient subgroups.
Discussion
The findings suggest that the ME/CFS ‘secretome’ is dominated by intensified regulatory interactions involving the vasculature and metabolic regulation. A key strength is the use of high-plex proteomics, though the descriptive nature of the results requires further functional studies to confirm causality.
Conclusion & Future Work
The study concludes that ME/CFS involves a multifaceted pathophysiology driven by coordinated immune, vascular, and metabolic disturbances. These systemic proteome patterns offer a promising framework for future biomarker discovery and therapeutic development.