Key points
- A team of researchers have identified a blood test which, in a small exploratory study, was found to diagnose ME/CFS with 96% accuracy.
- The test looks at ‘chromosome conformations’ (the way genetic material is folded in cells), and whether these are specific to a disease.
- Importantly, variations of the test have been used successfully to diagnose other diseases including prostate cancer and Rheumatoid arthritis.
- Despite the promising results, the study was limited by factors including:
- Small sample size (47 people with severe ME/CFS and 61 healthy controls)
- Lack of disease control groups – it is not possible to tell from the results whether the test could differentiate between ME/CFS and another disease.
- Before any conclusions can be drawn, more research is needed in larger groups of participants to assess whether the blood test is able to identify people with other severity levels of ME/CFS, and importantly, whether the test can differentiate between ME/CFS and other diseases.
Background
Based on the results of a small, ‘proof of concept’– early phase, or exploratory – study, a team of researchers from the University of East Anglia, led by Dr Dimitri Pchejetski, say they have developed a blood test which can differentiate between people have ME/CFS and heathy controls with 96% accuracy.
Why is this important?
Despite numerous studies demonstrating biological changes related to ME/CFS, a validated diagnostic biomarker has not yet been identified. Currently, the diagnosis of ME/CFS is largely based on self-reported measures and the exclusion of other medical conditions using criteria such as the NICE 2021 criteria for ME/CFS, the IOM 2015 Criteria for ME/CFS, and the International Consensus Criteria (ICC) for ME.
Regrettably existing criteria do not use consistent definitions for the disease, and some, for example the Fukuda criteria for CFS, do not require post exertional malaise (PEM) – the cardinal symptom of ME/CFS – for a diagnosis to be made.
The lack of a validated biomarker leaves the door open for misunderstanding and misdiagnosis, limits the comparability of research where studies use different definitions for the disease, and increases the differences (disease heterogeneity) between people with ME/CFS in studies – something that can lead to misleading results.
An accurate biomarker for ME/CFS would not only improve diagnosis in health care settings, but would also reduce heterogeneity in research, undoubtably leading to improved understanding of the disease, and consequently, reduced stigma.
How does the test work?
The way in which genetic material (deoxyribonucleic acid, DNA) folds – chromosome conformations (CCs) – inside a cell may play a role in how the body uses the information stored inside the DNA (gene expression).
In 2005, Dr Dimitri Pchejetski and colleagues developed a test, called “EpiSwitch”, which can identify CCs linked to different diseases.
Importantly, the “EpiSwitch” test has successfully been used to identified disease specific CCs in peripheral blood mononuclear cells (PBMCs) – a type of blood cell which plays a critical role in the immune system – of people with:
- Severe COVID-19
- Rheumatoid arthritis
- Prostate or colorectal cancers
- Diffuse large B-cell lymphoma
- Motor neurone disease (MND), also known as amyotrophic lateral sclerosis (ALS).
Given the previous success of the test, the researchers carried out a study which aimed to investigate whether this test was also able to identify CCs specific to ME/CFS, and if so, whether the test may act as a potential diagnostic tool for the disease.
What did the researchers do?
The study compared blood samples from the London School of Hygiene and Tropical Medicine Biobank – established with a joint grant from the charities including ME Research UK – from 47 people with severe ME/CFS who were housebound, with those from 20 age-matched healthy controls. Blood samples for another 41 controls were obtained from the ‘OBD repository’, although no reference was provided to for this resource.
The researchers also used information that had been collected on symptoms, and on physical functioning using the RAND-36 questionnaire, and assessed how markers in the blood correlated with results from these questionnaires.
What do the findings show?
Results suggested that there were indeed significant differences between the blood samples taken from those with ME/CFS compared with those from healthy controls – and that there did appear to be CCs specific to ME/CFS.
In fact, the test was found to be 96% accurate, meaning that:
- Sensitivity was 92% – the test could correctly identify those who had ME/CFS 92% of the time.
- Specificity was 98% – the test was able to correctly identify those who did not have the disease 98% of the time.
Importantly, the findings from this study indicated that changes in immune and mitochondrial genes correlated with physical functioning, something which the authors suggest may provide evidence of biological links to fatigue and PEM.
Notably, the authors state that the pathways linked to ME/CFS in this analysis, have also been implicated in other inflammatory and neuroimmune conditions including Multiple Sclerosis, Rheumatoid Arthritis, and Alzheimer’s disease.
Limitations of the study
There were several limitations of the study acknowledged by the authors, including:
- Small sample size – this was a proof-of-concept study which only included a small number of participants. Before any firm conclusions can be drawn, this research must be replicated in larger groups of participants.
- Only included those with severe ME/CFS; while this is a strength as this group of participants are often not included in research, more research is needed to assess whether the results of this study could be replicated in those with mild, moderate, and very severe forms of the disease.
- The comparison group only included healthy controls, therefore it is not possible to assess how well this test is able to differentiate between people with ME/CFS and other diseases – especially those with overlapping symptoms, such as long COVID, fibromyalgia, Lyme disease, and Multiple Sclerosis.
ME Research UK notes that there was also a difference in sex ratio between the ME/CFS group and the control group; while the ME/CFS group included 8 males and 39 females, the control group included 39 males and 22 females. As there is evidence of biological differences between males and females with the disease, future studies should control for sex in the analysis, or match participants on sex. It would also be essential to look at whether the test had the same accuracy in both males and females with the disease.
What do the findings mean?
Although promising, due to the limitations of the study, the results must be interpreted with caution. More research is needed in larger groups of participants to assess whether the blood test is able to identify people with other severity levels of ME/CFS, and importantly, whether the test can differentiate between ME/CFS and other diseases. It would also be important to assess the effectiveness of the test in different groups of the population who are often not represented in ME/CFS research (underserved groups) such as black and minority ethnic groups, and men with the disease.
