Image description. Two people dressed in white coats examine research with a clipboard and microscope. Inset pictures feature red blood cells and the other data analysis results. ME Association logo (bottom right) The title reads: Research: Biomarkers for ME/CFS: A Systemic Review.

Research: Biomarkers for ME/CFS: A Systemic Review. 

BMC Medicine

by Rebekah Maksoud, Chandi Magawa, Natalie Eaton-Fitch, Kiran Thapaliya, Sonya Marshall- Gradisnik

This is a comprehensive review of all the potential biomarkers for ME/CFS that have been assessed in the past, or are currently being assessed.

For a blood test, or any other investigation, to achieve the status of being an objective biomarker for a disease it has be positive in all, or a very high percentage of people with the condition and it should not be positive in any other condition that has similar symptoms.

As the review points out there are a considerable number of blood and other abnormalities that have the potential to become biomarkers for ME/CFS.
However, in our current state of knowledge, none of them can be regarded as being reliable when it comes to differentiating people with ME/CFS from people who have other health conditions, or are perfectly healthy.

Dr Charles Shepherd,
Trustee and
Hon. Medical Adviser
to the ME Association.

Dr Charles Shepherd



Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multifaceted condition that affects most body systems.

There is currently no known diagnostic biomarker; instead, diagnosis is dependent on application of symptom-based case criteria following exclusion of any other potential medical conditions. While there are some studies that report potential biomarkers for ME/CFS, their efficacy has not been validated.

The aim of this systematic review is to collate and appraise literature pertaining to a potential biomarker(s) which may effectively differentiate ME/CFS patients from healthy controls.


A total of 101 publications were included in this systematic review.

Potential biomarkers ranged from genetic/epigenetic (19.8%), immunological (29.7%), metabolomics/mitochondrial/microbiome (14.85%), endovascular/circulatory (17.82%), neurological (7.92%), ion channel (8.91%) and physical dysfunction biomarkers (8.91%).

Most of the potential biomarkers reported were blood-based (79.2%). Use of lymphocytes as a model to investigate ME/CFS pathology was prominent among immune-based biomarkers.

Most biomarkers had secondary (43.56%) or tertiary (54.47%) selectivity, which is the ability for the biomarker to identify a disease-causing agent, and a moderate (59.40%) to complex (39.60%) ease-of-detection, including the requirement of specialised equipment.


All potential ME/CFS biomarkers differed in efficiency, quality, and translatability as a diagnostic marker.

Reproducibility of findings between the included publications were limited, however, several studies validated the involvement of immune dysfunction in the pathology of ME/CFS and the use of lymphocytes as a model to investigate the pathomechanism of illness.

The heterogeneity shown across many of the included studies highlights the need for multidisciplinary research and uniform protocols in ME/CFS biomarker research.

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