Review The search for a blood-based biomarker for [ME/CFS]: from biochemistry to electrophysiology, 2025, Clarke et al

Abstract
Background
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disease of unknown aetiology characterised by symptoms of post-exertional malaise (PEM) and fatigue leading to substantial impairment in functioning. Other key symptoms include cognitive impairment and unrefreshing sleep, with many experiencing pain. To date there is no complete understanding of the triggering pathomechanisms of disease, and no quantitative biomarker available with sufficient sensitivity, specificity, and adoptability to provide conclusive diagnosis. Clinicians thus eliminate differential diagnoses, and rely on subjective, unspecific, and disputed clinical diagnostic criteria—a process that often takes years with patients being misdiagnosed and receiving inappropriate and sometimes detrimental care. Without a quantitative biomarker, trivialisation, scepticism, marginalisation, and misunderstanding of ME/CFS continues despite the significant disability for many. One in four individuals are bed-bound for long periods of time, others have difficulties maintaining a job/attending school, incurring individual income losses of thousands, while few participate in social activities.

Main body
Recent studies have reported promising quantifiable differences in the biochemical and electrophysiological properties of blood cells, which separate ME/CFS and non-ME/CFS participants with high sensitivities and specificities—demonstrating potential development of an accessible and relatively non-invasive diagnostic biomarker. This includes profiling immune cells using Raman spectroscopy, measuring the electrical impedance of blood samples during hyperosmotic challenge using a nano-electronic assay, use of metabolomic assays, and certain techniques which assess mitochondrial dysfunction. However, for clinical application, the specificity of these biomarkers to ME/CFS needs to be explored in more disease controls, and their practicality/logistics considered. Differences in cytokine profiles in ME/CFS are also well documented, but finding a consistent, stable, and replicable cytokine profile may not be possible. Increasing evidence demonstrates acetylcholine receptor and transient receptor potential ion channel dysfunction in ME/CFS, though how these findings could translate to a diagnostic biomarker are yet to be explored.

Conclusion
Different biochemical and electrophysiological properties which differentiate ME/CFS have been identified across studies, holding promise as potential blood-based quantitative diagnostic biomarkers for ME/CFS. However, further research is required to determine their specificity to ME/CFS and adoptability for clinical use.

Link | PDF (J. Transl. Med., February 2025, open access)

 

Sometimes a literature review like this can be the first step before starting a project. Perhaps this final line of the abstract is an alley-oop for the next phase of work she will be doing?

>However, further research is required to determine their specificity to ME/CFS and adoptability for clinical use.

 

This is the team that is doing the nanoneedle replication attempt iirc.

 

Scanning it this seems like a good review that got the limitations of my old discriminator paper correct! Fingers crossed that they find success w the nanoneedle work

 

What do we think this means in the context of the nanoneedle study? Is this paper outlining a need in research ahead of publication, or does this mean they are broadening their scope because the nanoneedle has failed?

Last summer they were saying it was looking very good as a diagnostic thus far.

In fact , they claimed that they had already replicated the davis study.

Hopefully they will publish something soon.