Second place in ME Research UK’s Founders’ Science Writing Award went to Krista Clarke, who is a postdoctoral research fellow at the University of Surrey. Here is Krista’s entry on the development of quantitative diagnostic biomarkers for ME/CFS.
The future of ME/CFS research lies in the development of quantitative diagnostic biomarkers for ME/CFS. A biomarker is a characteristic that can be objectively measured to determine whether someone has a certain disease or not. A literature review on biomarkers by Maksoud and colleagues evaluated many pathophysiological differences in ME/CFS which could be used as diagnostic biomarkers.
However, it is very hard to find a biomarker which allows for quick and easy point-of-care diagnosis in clinics, uses techniques which are low-cost and easily adoptable, is reproducible by many different laboratories, and is accurate and specific enough to differentiate ME/CFS from other diseases with similar symptom presentation, such as multiple sclerosis and fibromyalgia.
Finding a diagnostic biomarker is important to remove the stigma of ME/CFS, prevent misdiagnosis, and accelerate receipt of correct treatment plans. A quantifiable biomarker would also provide greater insight into the mechanism behind ME/CFS and drive the focus of drugs that could treat ME/CFS.
Diagnostic criteria
To facilitate the development of a quantifiable diagnostic biomarker, it is first very important to consider donor recruitment to research studies. There is a great necessity to standardise the criterion used currently to diagnose ME/CFS, and to provide a consensus on what counts as ME/CFS.
It is advised by the National Institutes of Health that the Fukuda criteria are not used. However, given the heterogeneity of other criteria such as the International Consensus Criteria (2011), the Canadian Consensus Criteria (2003), and the Institute of Medicine Criteria (2015), the problem remains that different research studies and clinical trials are recruiting different patient populations. This limits the reproducibility between biomarker studies and increases the subjectivity of results. Instead, it would be beneficial to standardise ME/CFS donor recruitment to research studies and clinical trials.
Importance of subgroups
There is also a need for all studies to stratify recruited donors into smaller subgroups, to personalise biomarker development. The performance of any potential biomarker needs to be assessed against variables including patient age, body mass index, ME/CFS onset trigger, and duration of symptoms – all of which have been shown to affect body/cell function.
Moreover, due to the heterogenous presentation of symptoms in ME/CFS, symptom-based patient clusters are needed to understand whether different pathological mechanisms cause different ME/CFS phenotypes – and would thus necessitate different biomarkers.
Given the similarities of ME/CFS and long-COVID, it raises the question as to whether ME/CFS is one disease, or whether ME/CFS is an umbrella term for lots of diseases which share the same phenotype. Therefore, it is important to stratify patients, for example, based on immune competence, when investigating diagnostic biomarkers or treatments.
Although this has been impeded by lack of funding and resources, large donor cohorts are needed to be able to stratify patients into smaller subgroups and determine whether patient “outliers” who do not fit the trend of other donors, so-called “non-responders”, are part of a different ME/CFS subgroup.
Practical considerations
It is vital that during the development of potential biomarkers, the adoptability of protocols, the ease of sample collection, and the cost of equipment is considered. The need to obtain or isolate certain cell types and use high-cost technical machinery increases the time and complexity of biomarker development.
Where possible, a biomarker which solely requires whole blood would be beneficial as it is minimally invasive and would not require the laboratory equipment needed to isolate a certain cell type – facilitating point-of-care diagnostic methods. Cross-disciplinary collaboration with biomedical engineers would benefit the logistics of biomarker development.
Collaboration and updates
Finally, the progression and acceleration of ME/CFS biomarker research lies in multi-centre collaboration and research updates. It is very important to continue to share research updates quickly – including experiments which have not worked. Blogs and platforms such as X and YouTube have been incredibly useful at providing updates on research findings and hypotheses.
It would be further beneficial to also develop a centralised website, on which researchers from each international ME/CFS research group have their own dedicated web page. Researchers could then update fellow researchers and the public using either posts or multimedia on their page, listing their current experimental theme/focus, show preliminary results, and summaries of what they found/did not find. This could help foster collaboration between research groups and accelerate the dissemination of findings before publication.
