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Charting the circulating proteome in ME/CFS using cross-system profiling to uncover mechanistic insights
August Hoel1, Fredrik Hoel2, Sissel Elisabeth Dyrstad2
1Department of Biomedicine, University of Bergen, Bergen, Norway; Department of Clinical Medicine, University of Bergen, Bergen, Norway.
Cell Reports. Medicine
|March 5, 2026
Summary
Researchers identified distinct serum protein patterns in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) patients using aptamer proteomics. These findings may aid in understanding ME/CFS pathophysiology and developing future biomarkers and treatments.
Area of Science:
- Biochemistry
- Immunology
- Proteomics
Background:
- Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, debilitating illness with unknown causes and no specific treatments or biomarkers.
- Infections often precede ME/CFS onset, suggesting a role for immune system dysregulation.
Purpose of the Study:
- To investigate serum proteome differences between ME/CFS patients and healthy individuals using aptamer-based proteomics.
- To identify potential biomarkers and understand the underlying pathophysiology of ME/CFS.
Main Methods:
- Aptamer-based serum proteomics was performed on 50 ME/CFS patients and 29 healthy controls, analyzing 7,326 protein targets.
- Statistical analysis, including false discovery rate (FDR) correction, was used to identify significant protein differences.
- Selected protein findings were validated using antibody-based methods.
Main Results:
- 1,823 aptamers showed significant differences between groups (845 after FDR correction).
- ME/CFS patients exhibited increased secreted proteins and reduced intracellular proteins, particularly from skeletal muscle.
- Distinct immune cell signatures indicated immune reprogramming, with reduced proteins from activated neutrophils and intensified regulatory interactions in immunity, inflammation, vasculature, and metabolism.
Conclusions:
- The study identified unique serum proteome patterns in ME/CFS patients, suggesting significant pathophysiological alterations.
- These findings provide a foundation for future biomarker discovery and therapeutic strategies for ME/CFS.

