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Researcher
Prof. Bhupesh Prusty
Institution
Riga Stradins University, Riga, Latvia
Start date
August 2025
Funding
ME Research UK
Background
Our immune system is responsible for protecting our body from infections such as viruses and bacteria, recognising and destroying harmful substances from the environment, and combating changes in the body that can cause disease.
The role of the immune system in the development of ME/CFS has been widely researched, and several studies funded by ME Research UK have explored various aspects of abnormal immune function in the illness.
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.
Some immunoglobulins (autoantibodies) are directed against the body’s own proteins, cells or tissues. While these may have useful functions (such as destroying cancers or removing waste), they can lead to the development of a so-called autoimmune disease such as multiple sclerosis or lupus.
Autoimmune mechanisms have been suggested to be involved in ME/CFS, but the findings to date have been inconclusive, due partly to the complexity of the disease and differences between individuals.
Prof. Bhupesh Prusty’s previous research (funded by ME Research UK with the financial support of the Gordon Parish Charitable Trust) found that immunoglobulins taken from people with ME/CFS caused dysfunction of the mitochondria when mixed with cells taken from healthy individuals (these results are still to be published in a peer-reviewed journal).
The mitochondria are responsible for generating energy in the body, so these findings may have important implications for our understanding of ME/CFS.
Prof. Prusty wants to explore this further, and his new study will investigate the mechanisms through which immunoglobulins from ME/CFS patients can cause this mitochondrial dysfunction in cells.
Objectives
The researchers will first take immunoglobulin samples from people with ME/CFS and from healthy volunteers, and then culture them for 12 hours with healthy muscle and nerve cells, both of which are known to be affected in the disease.
The human brain is particularly complicated and experiments using single cells do not always reflect this. So immunoglobulins will also be cultured with three-dimensional brain tissue to fully understand the pathogenic processes.
Sequencing methods will be used to assess how the genes of these cells and tissues change their activity level in response to being exposed to the immunoglobulins, which will help to identify which cellular pathways are involved.
Immunoglobulins can have specific protein targets on the cells with which they interact, and a second part of the study is to investigate the exact molecular mechanism by which this interaction occurs.
Proteins will be extracted from a number of different cell types, including muscle, nerve, endothelial and immune cells, and then these proteins will be exposed to the immunoglobulins. Various techniques will be used to identify potential target proteins for the pathogenic immunoglobulins
Potential benefits
The researchers anticipate that their findings will provide a better understanding of the role of autoimmunity in ME/CFS, and specifically the molecular mechanism by which immunoglobulins can cause mitochondrial dysfunction. This could help in the design or selection of suitable treatments to target this pathway.
