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.