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.
Clarke et al (2025), Journal of Translational Medicine
On the 4th February 2025, the Journal of Translational Medicine published the following paper on ‘The search for a blood-based biomarker for Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS): from biochemistry to electrophysiology'.
This paper was written by Dr Krista Clarke and colleagues at the University of Surrey and members of the ME/CFS Biobank team at the London School of Hygiene and Tropical Medicine (LSHTM), and was fully funded by MEA Ramsay Research Fund and ME Research UK (MERUK)
Extracts
Background
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.
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.
MEA Comment
This paper, covering the development of diagnostic biomarkers for ME/CFS, comes from Dr Krista Clarke and colleagues at the University of Surrey and members of the ME Biobank team at the London School of Hygiene and Tropical Medicine.
The biomarker research at the University of Surrey is being funded by the MEA Ramsay Research Fund and MERUK and is using blood samples from the ME Biobank.
All the basic running costs for the ME Biobank – approximately £80,000 per annum – are paid by the MEA Ramsay Research Fund.
Dr Charles Shepherd,
Trustee and Hon. Medical Adviser to the ME Association,
Member of the 2018-2021 NICE guideline on ME/CFS committee,
Member of the 2002 Chief Medical Officer's Working Group on ME/CFS
Chair, ME Biobank Steering Group
More Information
- The ME Association and ME Research UK announce funding for a study that aims to create a diagnostic test for ME/CFS | October 30, 2023
- Professor Robert Dorey and colleagues update on investigating the electrical properties of blood from people with ME/CFS | July 2, 2024
- MEA and MERUK Research: Explaining Electrophysiological Properties of Cells in Health and Disease | August 15, 2024
- ME Research UK: Electrophysiological properties of cells in health and disease | August 30, 2024