Biomarkers for ME/CFS: a systematic review
Australian researchers found 101 key studies in ME/CFS that varied in efficacy, quality, and potential to be developed into a diagnostic biomarker. Most were blood-based and measured a range of dysfunction.
“Many of these biomarkers were studied in isolation but may be part of a complex multidisciplinary process as displayed by some of the overlap between observations made and extensive crosstalk between each system. There is evidence of widespread genetic, immune, neurological, mitochondrial and endocrine differences in ME/CFS compared with healthy controls.”
Immune dysfunction appeared to be key and the use of lymphocytes a potential model, which are a type of white blood cell in the immune system and include natural killer cells, T cells, and B cells. To aid future biomarker research the researchers concluded there is a need for multidisciplinary research and uniform protocols.
Postulated multidisciplinary pathway of ME/CFS
Biomarkers for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a systematic review, by Rebekah Maksoud, Chandi Magawa, Natalie Eaton-Fitch, Kiran Thapaliya & Sonya Marshall-Gradisnik in BMC Medicine vol 21, no: 189 (2023) [doi.org/10.1186/s12916-023-02893-9]
Review abstract:
Background
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.
Methods
This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Cochrane review guidelines. PubMed, Embase and Scopus were systematically searched for articles containing “biomarker” and “ME/CFS” keywords in the abstract or title and if they included the following criteria:
(1) were observational studies published between December 1994 and April 2022;
(2) involved adult human participants;
(3) full text is available in English
(4) original research;
(5) diagnosis of ME/CFS patients made according to the Fukuda criteria (1994), Canadian Consensus Criteria (2003), International Consensus Criteria (2011) or Institute of Medicine Criteria (2015);
(6) study investigated potential biomarkers of ME/CFS compared to healthy controls. Quality and Bias were assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Case Control Studies.
Results
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.
Conclusions
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.
