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Circulating levels of GDF15 in patients with myalgic encephalomyelitis/chronic fatigue syndrome
A Melvin1, E Lacerda2, H M Dockrell2,3
1MRC Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Addenbrookes Treatment Centre, Cambridge, CB2 0QQ, UK.
Background:
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating condition characterised by fatigue and post-exertional malaise. Its pathogenesis is poorly understood. GDF15 is a circulating protein secreted by cells in response to a variety of stressors. The receptor for GDF15 is expressed in the brain, where its activation results in a range of responses. Among the conditions in which circulating GDF15 levels are highly elevated are mitochondrial disorders, where early skeletal muscle fatigue is a key symptom. We hypothesised that GDF15 may represent a marker of cellular stress in ME/CFS.
Methods:
GDF15 was measured in serum from patients with ME/CFS (n = 150; 100 with mild/moderate and 50 with severe symptoms), "healthy volunteers" (n = 150) and a cohort of patients with multiple sclerosis (n = 50).
Results:
Circulating GDF15 remained stable in a subset of ME/CFS patients when sampled on two occasions ~ 7 months (IQR 6.7-8.8) apart, 720 pg/ml (95% CI 625-816) vs 670 pg/ml (95% CI 598-796), P = 0.5. GDF15 levels were 491 pg/ml in controls (95% CI 429-553), 546 pg/ml (95% CI 478-614) in MS patients, 560 pg/ml (95% CI 502-617) in mild/moderate ME/CFS patients and 602 pg/ml (95% CI 531-674) in severely affected ME/CFS patients. Accounting for potential confounders, severely affected ME/CFS patients had GDF15 concentrations that were significantly increased compared to healthy controls (P = 0.01). GDF15 levels were positively correlated (P = 0.026) with fatigue scores in ME/CFS.
Conclusions:
Severe ME/CFS is associated with increased levels of GDF15, a circulating biomarker of cellular stress that appears which stable over several months.
Insights
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is linked to higher GDF15 levels, a marker of cellular stress. These GDF15 levels remain stable over time in ME/CFS patients, suggesting a potential biomarker for the condition.
Area of Science:
- Biochemistry
- Immunology
- Neuroscience
Background:
- Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex condition with poorly understood pathogenesis.
- Elevated GDF15, a stress-induced protein, is observed in conditions like mitochondrial disorders with skeletal muscle fatigue.
- GDF15 signaling in the brain suggests a potential role in conditions involving fatigue.
Purpose of the Study:
- To investigate GDF15 as a potential biomarker for cellular stress in ME/CFS.
- To compare GDF15 levels in ME/CFS patients with healthy controls and multiple sclerosis patients.
Main Methods:
- Serum GDF15 levels were measured in 150 ME/CFS patients (mild/moderate and severe), 150 healthy volunteers, and 50 multiple sclerosis patients.
- GDF15 stability was assessed in a subset of ME/CFS patients over approximately 7 months.
- Statistical analyses were performed to compare GDF15 levels and correlate them with fatigue scores.
Main Results:
- GDF15 levels were stable over time in ME/CFS patients.
- Severely affected ME/CFS patients showed significantly increased GDF15 concentrations compared to healthy controls (P=0.01).
- GDF15 levels positively correlated with fatigue scores in ME/CFS patients (P=0.026).
Conclusions:
- Severe ME/CFS is associated with elevated circulating GDF15 levels.
- GDF15 serves as a stable biomarker of cellular stress in ME/CFS.
- GDF15 warrants further investigation as a potential diagnostic or prognostic marker for ME/CFS.
