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Circulating levels of GDF15 in patients with myalgic encephalomyelitis/chronic fatigue syndrome.

Published version
Peer-reviewed

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Article

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Authors

Lacerda, E 
Dockrell, H M 
O'Rahilly, S 
Nacul, L 

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.

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Keywords

Chronic fatigue Syndrome, Myalgic Encephalomyelitis, Gdf15

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Journal ISSN

1479-5876

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Sponsorship
National Institute of Allergy and Infectious Diseases (R01AI103629)
ME Association (PF8947_ME Association)
Wellcome Trust (214274/Z/18/Z, WT 214274/Z/18/Z)
Medical Research Council (MRC_MC_UU_12012.1)