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

• Published in: Journal of translational medicine 2019-12, Vol.17 (1), p.409-409, Article 409
• Main Authors: Melvin, A, Lacerda, E, Dockrell, H M, O'Rahilly, S, Nacul, L
• Format: Article
• Language: English
• Subjects: Adult; Biomarkers; Care and treatment; Case-Control Studies; Chronic diseases; Chronic fatigue syndrome; Disease; Encephalomyelitis; Fatigue; Fatigue Syndrome, Chronic - blood; Female; Follow-Up Studies; GDF15; Growth Differentiation Factor 15 - blood; Herpes viruses; Humans; Laboratories; Linear Models; Longitudinal Studies; Male; Measurement methods; Middle Aged; Mitochondria; Multiple sclerosis; Multivariate Analysis; Muscle fatigue; Muscles; Myalgic encephalomyelitis; Outcome Assessment, Health Care; Pain; Questionnaires; R&D; Regression analysis; Research & development; Self Report; Skeletal muscle; Time Factors
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-019-02153-6

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. 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). 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. Severe ME/CFS is associated with increased levels of GDF15, a circulating biomarker of cellular stress that appears which stable over several months.