Liu et al. (2026)
- Authors: Zheng Liu, Claudia Hollmann, Sharada Kalanidhi, Stephanie Lamer, Andreas Schlosser, Emils Edgars Basens, Georgy Nikolayshvili, Liba Sokolovska, Gabriela Riemekasten, Rebekka Rust, Judith Bellmann-Strobel, Friedemann Paul, Carmen Scheibenbogen, Bhupesh K. Prusty
- Institutes: Charité – Universitätsmedizin Berlin, Germany, Julius-Maximilians-University of Würzburg, Germany, University of Lübeck, Germany, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany
- Publisher: Brain, Behavior, & Immunity - Health
- Link: DOI
Summary
This study identifies a direct mechanistic link between the immune system and energy failure in ME/CFS and Long COVID. By showing that patient antibodies cause mitochondria to fragment, it explains why patients experience profound exhaustion and crashes after exertion. These findings validate the biological reality of the disease and provide specific cellular targets for future diagnostic tests and treatments.
What was researched?
The study investigated whether Immunoglobulin G (IgG) complexes from patients with post-infectious ME/CFS and post-COVID ME/CFS could disrupt cellular energy production and trigger inflammation. Researchers specifically looked at the effects of these antibodies on human endothelial cells and immune cells.
Why was it researched?
While autoimmunity is suspected in ME/CFS, the exact process by which antibodies cause symptoms like extreme fatigue remains unclear. Researchers aimed to find a mechanistic explanation for how patient-derived immunoglobulins affect mitochondrial function and cellular health.
How was it researched?
The team isolated IgG from 106 individuals, including those with ME/CFS, post-COVID ME/CFS, Multiple Sclerosis, and healthy controls. They applied these antibodies to healthy human endothelial cells and immune cells, then measured mitochondrial structure, energy metabolism, and cytokine secretion using Seahorse metabolic flux analysis and mass spectrometry-based proteomics.
What has been found?
IgG from ME/CFS and post-COVID patients selectively induced mitochondrial fragmentation and metabolic reprogramming in endothelial cells, an effect driven by the Fab portion of the antibody. Proteomic analysis showed that ME/CFS immune complexes were linked to extracellular matrix changes, while post-COVID complexes were associated with blood clotting issues. Additionally, patient-derived IgG triggered distinct inflammatory cytokine profiles in healthy immune cells.
Discussion
The findings suggest a chronic stress-adaptive state where mitochondrial capacity is not destroyed but becomes highly vulnerable to increased demand. This “threat-adapted” state helps explain why patients appear stable at rest but suffer physiological collapse during exertion. The study emphasizes the role of the endothelium in the systemic nature of the disease.
Conclusion & Future Work
The research demonstrates that IgG antibodies in ME/CFS carry a signal that forces mitochondria into a fragmented, stressed state. These findings suggest that targeting antibody-mediated metabolic dysregulation could be a viable therapeutic strategy. Future research should focus on treatments that can reverse this mitochondrial fragmentation and restore normal energy reserves.