The search for a blood-based biomarker for Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS): from biochemistry to electrophysiology
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...
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2025-02-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-025-06146-6 |
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| author | Krista S. P. Clarke Caroline C. Kingdon Michael Pycraft Hughes Eliana Mattos Lacerda Rebecca Lewis Emily J. Kruchek Robert A. Dorey Fatima H. Labeed |
| author_facet | Krista S. P. Clarke Caroline C. Kingdon Michael Pycraft Hughes Eliana Mattos Lacerda Rebecca Lewis Emily J. Kruchek Robert A. Dorey Fatima H. Labeed |
| author_sort | Krista S. P. Clarke |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-6556c6ac884e4a6595392dbf21fc12b8 |
| institution | Kabale University |
| issn | 1479-5876 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
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| series | Journal of Translational Medicine |
| spelling | doaj-art-6556c6ac884e4a6595392dbf21fc12b82025-02-09T12:52:28ZengBMCJournal of Translational Medicine1479-58762025-02-0123113310.1186/s12967-025-06146-6The search for a blood-based biomarker for Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS): from biochemistry to electrophysiologyKrista S. P. Clarke0Caroline C. Kingdon1Michael Pycraft Hughes2Eliana Mattos Lacerda3Rebecca Lewis4Emily J. Kruchek5Robert A. Dorey6Fatima H. Labeed7Centre for Biomedical Engineering, School of Engineering, University of SurreyDepartment of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical MedicineDepartment of Biomedical Engineering and Biotechnology/Healthcare Engineering Innovation Center, Khalifa UniversityDepartment of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical MedicineDepartment of Comparative Biomedical Sciences, School of Veterinary Medicine, University of SurreyCentre for Biomedical Engineering, School of Engineering, University of SurreyCentre for Biomedical Engineering, School of Engineering, University of SurreyDepartment of Biology, United Arab Emirates UniversityAbstract 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.https://doi.org/10.1186/s12967-025-06146-6ME/CFSPeripheral blood mononuclear cellNatural killer cellMitochondrial dysfunctionRaman spectroscopyMetabolomic assay |
| spellingShingle | Krista S. P. Clarke Caroline C. Kingdon Michael Pycraft Hughes Eliana Mattos Lacerda Rebecca Lewis Emily J. Kruchek Robert A. Dorey Fatima H. Labeed The search for a blood-based biomarker for Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS): from biochemistry to electrophysiology Journal of Translational Medicine ME/CFS Peripheral blood mononuclear cell Natural killer cell Mitochondrial dysfunction Raman spectroscopy Metabolomic assay |
| title | The search for a blood-based biomarker for Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS): from biochemistry to electrophysiology |
| title_full | The search for a blood-based biomarker for Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS): from biochemistry to electrophysiology |
| title_fullStr | The search for a blood-based biomarker for Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS): from biochemistry to electrophysiology |
| title_full_unstemmed | The search for a blood-based biomarker for Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS): from biochemistry to electrophysiology |
| title_short | The search for a blood-based biomarker for Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS): from biochemistry to electrophysiology |
| title_sort | search for a blood based biomarker for myalgic encephalomyelitis chronic fatigue syndrome me cfs from biochemistry to electrophysiology |
| topic | ME/CFS Peripheral blood mononuclear cell Natural killer cell Mitochondrial dysfunction Raman spectroscopy Metabolomic assay |
| url | https://doi.org/10.1186/s12967-025-06146-6 |
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