Researchers
Dr Andrea Polli & Prof. Lode Godderis
PhD student
Yanthe Buntinx
Institutions
Vrije Universiteit Brussel, Brussels, Belgium & Katholieke Universiteit Leuven, Leuven, Belgium
Start date
October 2025
Funding
ME Research UK with the financial support of the Gordon Parish Charitable Trust
Background
People with ME/CFS often mention that their disease started after an infection, or that they need longer than normal to recover from a cold or flu.
This suggests there might be some problem with the immune system in ME/CFS. However, we don’t understand whether the immune system is inherently weaker in people with the disease, or whether viruses and bacteria stay longer in the body making the immune system fight for so long that it becomes exhausted.
In this study, Dr Polli, Prof. Godderis, PhD student Yanthe Buntinx and their colleagues will explore whether the immune system in people with ME/CFS is exhausted by prolonged activation (immune exhaustion) or whether it is inherently weaker and more vulnerable (this is called immune senescence).
In both cases, the cells of the immune system are likely to be dysfunctional and less able to use energy to function. The researchers will therefore also study how these cells produce and use energy, and how that links to immune exhaustion and senescence.
Other experiments will investigate whether immune exhaustion can be reversed using available treatments such as immune checkpoint inhibitors, and whether markers of immune exhaustion and senescence can predict the occurrence of post-exertional malaise (PEM) following an exercise test.
Objectives
The study will include 60 people with ME/CFS (diagnosed using the Canadian Consensus Criteria) and 60 healthy volunteers matched for age, sex and body mass index.
All of these individuals were participants in two studies conducted by the researchers over the last 3 years, so much of their data has already been recorded, including assessments of ME/CFS symptoms using a number of validated questionnaires.
In addition, blood samples have already been collected before and after the participants underwent a physical stress procedure which induces PEM. Much of the work of the current study will be to analyse these samples for a variety of different measures.
- The expression of markers associated with immune exhaustion (PD-1, Tim-3, TIGIT, TCF-1, Tox, T-bet and Eomes).
- The expression of markers associated with immune senescence (CD57, KLRG1 and CD28).
- The response of dysfunctional immune cells (white blood cells) to treatment with immune checkpoint inhibitors.
- The metabolic profile of immune cells.
- Epigenetic changes to the DNA from immune cells; that is, genetic changes that can turn genes on or off.
Potential benefits
A better understanding of changes to the immune system in ME/CFS, and how immune cells produce and use energy, will not only help us understand the pathological mechanisms underlying the disease, but could guide new therapies targeting these mechanisms.
The researchers highlight that study of the immune system is much more advanced in diseases such as cancer, where the development of immunotherapies has revolutionised treatment. Their hope is that these breakthroughs can now be transferred to ME/CFS.
