Today a research paper entitled ‘Development and validation of blood-based diagnostic biomarkers for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) using EpiSwitch® 3-dimensional genomic regulatory immuno-genetic profiling‘ was published in the Journal of Translational Medicine.
Dr Charles Shepherd, MEA Hon. Medical Adviser, comments on the research that references biomarkers for the disease. He has spoken with journalists and has been quoted in the some of the mainstream media articles that are covering this paper this morning.
Abstract
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating, multifactorial disorder characterised by profound fatigue, post-exertional malaise, cognitive impairments, and autonomic dysfunction. Despite its significant impact on quality of life, ME/CFS lacks definitive diagnostic biomarkers, complicating diagnosis and management. Recent evidence highlights potential blood tests for ME/CFS biomarkers in immunological, genetic, metabolic, and bioenergetic domains.
Chromosome conformations (CCs) are potent epigenetic regulators of gene expression and cross-tissue exosome signalling. We have previously developed an epigenetic assay, EpiSwitch®, that employs an algorithm-based CCs analysis. Using EpiSwitch® technology, we have shown the presence of disease-specific CCs in peripheral blood mononuclear cells (PBMCs) of patients with amyotrophic lateral sclerosis (ALS), rheumatoid arthritis (RA), prostate and colorectal cancers, diffuse Large B-cell lymphoma and severe COVID-19. In a recent paper, we have identified a profile of systemic chromosome conformations in cancer patients reflective of the predisposition to respond to immune checkpoint inhibitors, PD-1/PD-L1 antagonists, with 85% accuracy. In this Retrospective case/control study (EPI-ME, Epigenetic Profiling Investigation in Myalgic Encephalomyelitis), we used whole blood samples retrospectively collected from n = 47 patients with severe ME/CFS and n = 61 age-matched healthy control patients to perform whole-genome 3D DNA screening for CCs correlating to ME/CFS diagnosis.
We identified a 200-marker model for ME/CFS diagnosis (Episwitch®CFS test). First testing on the retrospective independent validation cohort demonstrated a strong systemic ME/CFS signal with a sensitivity of 92% and a specificity of 98%.Pathways analysis revealed several likely contributors to the pathology of ME/CFS, including interleukins, TNFα, neuroinflammatory pathways, toll-like receptor signalling and JAK/STAT. Comparison with pathways involved in the action of Rituximab and glatiramer acetate (Copaxone) (therapies with potential in ME/CFS treatment) identified IL2 as a shared pathway with clear patient clustering, indicating a possibility of a potential responder group for targeted treatment.
MEA Comment
There are currently a number of research groups using different techniques to try and find a diagnostic blood test for ME/CFS. This includes two studies that are being funded by the ME Association Ramsay Research Fund and which are also using blood samples from the ME Biobank – which we fund.
These results, using epigenetic profiling, appear to be an important step forward in the search for a diagnostic blood test.
However, as the researchers point out, a diagnostic blood test has to be both highly sensitive and specific to that condition.
In this case, we therefore need to know whether the abnormality is consistently present in the very early stages of ME/CFS as well as in people with longstanding disease who have mild or moderate ME/CFS.
We also need to know that in addition to the abnormality not being present in healthy controls it is also not present in a range other chronic inflammatory and autoimmune diseases that cause ME/CFS like symptoms and form part of the differential diagnosis of ME/CFS.
Consequently, further research needs to be carried out to properly validate and repeat these findings before concluding that we do now have a highly sensitive and specific diagnostic blood test for ME/CFS.
Other biomarker research being funded by the MEA Ramsay Research Fund:
- University of Brunel: Research: Second-Phase Funding to Advance the Development of a Diagnostic Test for ME/CFS | Sept 10, 2025
- University of Oxford: Pre-Print Research: Developing a blood cell-based diagnostic test for ME/CFS using peripheral blood mononuclear cells | March 23, 2023
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
Further coverage:
Science Media Centre: Expert reaction to study of blood based diagnostic biomarkers for ME/CFS | October 8, 2025