Circulating levels of GDF15 in patients with myalgic encephalomyelitis/chronic fatigue syndrome.
Melvin, A, Lacerda, E, Dockrell, H M et al. · Journal of translational medicine · 2019 · DOI
Quick Summary
This study measured a protein called GDF15 in the blood of ME/CFS patients and compared it to healthy people. GDF15 is released by cells when they are stressed or damaged. The researchers found that patients with severe ME/CFS had higher levels of GDF15 than healthy controls, and the levels of this protein were linked to how tired patients felt. The GDF15 levels stayed relatively stable over several months, suggesting it could be a useful marker for measuring cellular stress in ME/CFS.
Why It Matters
ME/CFS lacks established biomarkers, making diagnosis challenging and disease tracking difficult. Identifying GDF15 as a potential biomarker that reflects disease severity could aid in objective disease assessment and monitoring. This finding suggests cellular stress mechanisms may underlie ME/CFS symptoms, opening new avenues for understanding the disease's biology and developing targeted treatments.
Observed Findings
Severe ME/CFS patients had significantly elevated GDF15 levels (602 pg/ml) compared to healthy controls (491 pg/ml, P=0.01)
Mild/moderate ME/CFS patients had intermediate GDF15 levels (560 pg/ml), suggesting a dose-response relationship with symptom severity
GDF15 levels were positively correlated with fatigue scores in ME/CFS patients (P=0.026)
GDF15 remained stable in a subset of ME/CFS patients across two measurements ~7 months apart
MS patients had GDF15 levels similar to mild/moderate ME/CFS patients and controls, suggesting the elevation is not a non-specific inflammatory response
Inferred Conclusions
Severe ME/CFS is associated with increased circulating GDF15, a marker of cellular stress
GDF15 levels correlate with fatigue severity, suggesting it may serve as a biomarker for disease status
GDF15 stability over months suggests it could be a reliable marker for longitudinal disease monitoring
Elevated GDF15 in ME/CFS, similar to patterns seen in mitochondrial disorders, may indicate impaired cellular energy metabolism as a disease mechanism
Remaining Questions
Does GDF15 elevation indicate mitochondrial dysfunction or other specific cellular stress pathways in ME/CFS?
What This Study Does Not Prove
This study does not prove that GDF15 causes ME/CFS or post-exertional malaise—it only shows an association. The elevated GDF15 may be a consequence of ME/CFS rather than a cause. The study does not establish GDF15 as a diagnostic test or explain the mechanisms by which GDF15 contributes to symptoms.