ME/CFS is a complex disease which differs between individuals, between groups of people with the disease, and even within the same individual over time. Understanding ME/CFS disease mechanisms is key to explaining this disease diversity (heterogeneity), and for developing targeted treatments.
Therefore, a collaborative study by a team of researchers with different yet complementary skillsets (a multidisciplinary research team) – including Dr Amy Proal and Dr Bo Bertilson who are currently working on projects funded by ME Research UK – aimed to identify:
- Biological pathways which were dysregulated in people with ME/CFS compared with healthy controls.
- Distinct groups of people with ME/CFS based on their immune profile (a comprehensive ‘snapshot’ of an individual’s immune system including information on how well it is working, and the components within it).
What did the researchers do?
The team of scientists recruited 40 people with ME/CFS – diagnosed using the Canadian Consensus Criteria (CCC), and 41 healthy controls who were the same age and sex.
Participants completed questionnaires relating to pain, fatigue, and quality of life. Additionally, those with ME/CFS had samples taken of cerebrospinal fluid (CSF) – the clear liquid that fills and surrounds the brain and the spinal cord.
Results from the study were complex, but in summary the researchers found that:
- Compared with healthy controls, participants with ME/CFS reported higher pain and fatigue levels, had scores indicating lower quality of life, and demonstrated slower walking speed.
- For people with ME/CFS, the most commonly reported disease triggers were infection (60%) and stress (33%).
- No differences were found between healthy controls and those with ME/CFS in relation to the pathogens they had been exposed to over their lifetime.
- Two distinct subtypes among participants with ME/CFS were identified based on immune profiles observed in CSF.
- Although these two groups of participants had very similar symptom profiles, significant differences were observed in relation to factors including the types of pathogens they had been exposed to.
Limitations
The researchers recognise that the study was limited by the relatively small sample size (81 participants in total) and that due to the invasive nature of the procedure, samples of CSF could only be taken from participants with ME/CFS.
What do the findings mean?
Importantly, these findings do not rule out the possibility that pathogens may act differently after exposure in those with ME/CFS compared with controls. In fact, in a recent talk at the PolyBio Spring 2025 Symposium, Dr Proal explained that after an initial infection, some pathogens may ‘hide’ in areas of the body where the immune system is less active – such as muscle tissue – and reactivate when the body is under stress causing “chronic complex illnesses” like ME/CFS. As this study – and many other ME/CFS studies – only used samples of body fluids like CSF, the results may not provide the full picture. Rather the researchers used their findings to highlight the need for tissue biopsy studies – such as the ME Research UK funded project being carried out by Dr Proal and her team – to investigate pathogen reactivation in people with ME/CFS further.
