E0 ConsensusPreliminaryPEM requiredSystematic-ReviewPeer-reviewedReviewed
Biomarkers for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a systematic review.
Maksoud, Rebekah, Magawa, Chandi, Eaton-Fitch, Natalie et al. · BMC medicine · 2023 · DOI
Quick Summary
Researchers reviewed 101 studies looking for biological markers (biomarkers) that could help diagnose ME/CFS. A biomarker is something measurable in your blood or body that shows a disease is present. While scientists found many potential biomarkers affecting the immune system, energy production, circulation, and other body functions, none have been proven reliable enough to use as a diagnostic test yet.
Why It Matters
ME/CFS currently lacks an objective diagnostic test, requiring symptom-based diagnosis after excluding other conditions. This review synthesizes evidence on potential biomarkers that could eventually enable faster, more accurate diagnosis and advance understanding of disease mechanisms. Identifying reliable biomarkers is essential for developing targeted treatments and validating ME/CFS as a biological disease.
Observed Findings
- Immunological biomarkers were the most frequently studied (29.7% of all biomarkers), with lymphocyte dysfunction appearing most prominent
- Most potential biomarkers were blood-based (79.2%), making them potentially accessible for clinical use
- The majority of identified biomarkers showed secondary (43.56%) or tertiary (54.47%) selectivity, meaning they lack high specificity for ME/CFS
- Biomarkers ranged across seven distinct categories, suggesting ME/CFS involves multiple biological systems
- Most biomarkers required moderate to complex detection methods (59.40% moderate, 39.60% complex), including specialized laboratory equipment
Inferred Conclusions
- Immune dysfunction appears to be a legitimate component of ME/CFS pathology based on multiple validated immune biomarker studies
- No single validated biomarker currently exists for ME/CFS diagnosis despite decades of research
- The field requires standardized protocols, larger cohort sizes, and multidisciplinary collaboration to advance biomarker research and clinical translation
Remaining Questions
- Which of the identified biomarkers (if any) will ultimately prove valid and reproducible enough for clinical diagnostic use?
- Why is there such poor reproducibility between studies investigating similar biomarkers—is it due to methodological differences, population heterogeneity, or true biological variability in ME/CFS?
What This Study Does Not Prove
This review does not establish that any single biomarker can diagnose ME/CFS in clinical practice—it reveals that none have been adequately validated yet. The heterogeneity and poor reproducibility across studies means findings from one research group often cannot be confirmed by others. This review identifies promising research directions but does not prove causation between identified markers and ME/CFS pathology.
Tags
Symptom:Fatigue
Biomarker:CytokinesMetabolomicsAutoantibodiesGene ExpressionBlood Biomarker
Method Flag:Exploratory OnlyMixed CohortPEM Not DefinedWeak Case Definition
Metadata
- DOI
- 10.1186/s12916-023-02893-9
- PMID
- 37226227
- Review status
- Editor reviewed
- Evidence level
- Established evidence from major reviews, guidelines, or evidence maps
- Last updated
- 12 April 2026
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
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