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Circulating levels of GDF15 in patients with myalgic encephalomyelitis/chronic fatigue syndrome.
J Transl Med. 2019 Dec 4;17(1):409. doi: 10.1186/s12967-019-02153-6.
Circulating levels of GDF15 in patients with myalgic
encephalomyelitis/chronic fatigue syndrome.
Melvin A, Lacerda E, Dockrell HM, 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.