Researchers
Zheng Liu, Bhupesh Prusty and colleagues
Institution
Institute of Virology and Immunobiology, University of Würzburg, Würzburg, Germany
Publication
Brain, Behavior, & Immunity – Health, 2026 March; 52:101187
Funding
ME Research UK with the financial support of the Gordon Parish Charitable Trust
Key findings
- Autoimmune mechanisms may be involved in the development of ME/CFS.
- Immunoglobulins (antibodies) were obtained from people with ME/CFS that had developed following an infection (including COVID), and were mixed with endothelial cells from healthy individuals.
- The immunoglobulins from a subgroup of patients caused fragmentation of the mitochondria of the healthy cells, as well as a change in how the cells produce and use energy.
- These results give further support to the idea that autoimmunity is involved in ME/CFS.
About the study
Prof. Bhupesh Prusty and his team have been investigating how viral infections may influence the development of ME/CFS.
The group’s research ties together three areas that are potentially important in the development of ME/CFS: the endothelium, the mitochondria and autoimmunity.
First, the endothelium. This is a thin layer of cells that lines the inner surface of every blood vessel. It is one of the largest organs in the body and is essential in regulating several important processes.
It controls blood flow by contracting and relaxing blood vessels, it regulates the passage of fluids from the blood to the tissues which allows the movement of immune cells; and it produces substances to prevent blood clotting.
There is a considerable body of evidence implicating endothelial dysfunction in the development of ME/CFS; in fact, some of the first studies funded by ME Research UK were in this area.
Second, the mitochondria. These are structures which are responsible for generating energy in every cell, and mitochondrial abnormalities have been implicated in ME/CFS, although the exact role is not yet clear.
Endothelial cells are highly reliant on mitochondrial signalling, so alterations in the mitochondria could have serious implications on endothelial function.
Third, autoimmunity. Immunoglobulins (also known as antibodies) play a key role in the immune system. They are proteins produced by the white blood cells which recognise and attack harmful invaders such as bacteria and viruses.
Autoantibodies are immunoglobulins which target the body’s own proteins, cells or tissues. They do have many useful functions such as destroying cancer cells or removing waste, but they can also lead to the emergence of autoimmune diseases such as multiple sclerosis or lupus.
The effects of autoimmunity may also play a role in the development of ME/CFS. However, there is a lack of clear evidence for this link, partly because the disease is so complex and because there is considerable variability between individuals.
Prof. Prusty’s hypothesis is that changes to the mitochondria seen in people with ME/CFS may be due to immunoglobulins transferred in the blood plasma, and this is what his team investigated in their recent study.
What did they do?
The researchers obtained immunoglobulins from blood samples taken from 106 individuals, including 39 people with ME/CFS that had developed following an infection, 15 people with ME/CFS following COVID, 20 people with multiple sclerosis, and 41 age-matched, healthy control subjects. ME/CFS was diagnosed based on the 2003 Canadian Consensus Criteria.
These immunoglobulins were then mixed with endothelial cells that had been obtained from heathy individuals and kept in carefully regulated laboratory conditions.
The effects on the mitochondria in the endothelial cells were assessed using a high-resolution microscope to examine their structure, and other lab techniques to look at cellular energy use and metabolism, and the secretion of proteins that cause inflammation.
What did they find?
In short, the researchers found that immunoglobulins from the blood of people with post-infectious ME/CFS caused disruption to the mitochondria of the healthy endothelial cells.
Specifically, they observed fragmentation, where the mitochondria divided into smaller parts. Mitochondrial fragmentation can occur as a normal response to stress or exercise, to allow damaged parts of the mitochondria to be removed. However, uncontrolled fragmentation has been linked to neurodegenerative diseases such as Parkinson’s disease.
It is worth noting that fragmentation was only seen in response to immunoglobulins from a subgroup of ME/CFS patients, and was more common using samples from women and those with post-COVID ME/CFS. Fragmentation was not seen when cells were exposed to immunoglobulins from patients with multiple sclerosis.
Immunoglobulins from people with ME/CFS also changed the cellular energetics of the endothelial cells; that is, the way in which the cells produce and use energy. However, the cells’ ability to generate ATP (often called the energy currency of the cell) was not altered.
Finally, immunoglobulins from ME/CFS patients also caused the production of chemicals known to stimulate inflammation, although it was not clear whether this finding was also linked with the mitochondrial fragmentation.
Conclusions
In summary, Prof. Prusty and his team found that immunoglobulins from a subgroup of people with post-infectious ME/CFS (including following COVID) caused fragmentation of the mitochondria in healthy endothelial cells. This did not affect the cells’ ability to generate ATP.
These results indicate that autoantibodies may therefore play a role in the development of ME/CFS following an infection, and give further support to the idea that autoimmunity is involved in the disease. The researchers therefore suggest considering treatment strategies for ME/CFS that target these autoantibodies.
ME Research UK is funding Prof. Prusty to follow up this work by looking more closely at the molecular mechanisms by which immunoglobulins can cause mitochondrial dysfunction.
