Circulating levels of GDF15 in patients with myalgic encephalomyelitis/chronic fatigue syndrome
Dockrell, H. M.
Journal of Translational Medicine
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Melvin, A., Lacerda, E., Dockrell, H. M., O’Rahilly, S., & Nacul, L. (2019). Circulating levels of GDF15 in patients with myalgic encephalomyelitis/chronic fatigue syndrome. Journal of Translational Medicine, 17 (1)https://doi.org/10.1186/s12967-019-02153-6
Abstract: 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.
Research, Illnesses of Unknown Etiology, GDF15, Myalgic encephalomyelitis, Chronic fatigue syndrome
Wellcome Trust (WT 214274/Z/18/Z)
Medical Research Council (MRC_MC_UU_12012.1)
National Institute of Allergy and Infectious Diseases (R01AI103629)
ME Association (PF8947_ME Association)
External DOI: https://doi.org/10.1186/s12967-019-02153-6
This record's URL: https://www.repository.cam.ac.uk/handle/1810/314458
Attribution 4.0 International (CC BY 4.0)
Licence URL: https://creativecommons.org/licenses/by/4.0/