Circulating levels of GDF15 in patients with myalgic encephalomyelitis/chronic fatigue syndrome. (Melvin et al 2019)

[Murph]

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 A1, Lacerda E2, Dockrell HM2,3, O'Rahilly S1, Nacul L4.
Author information
1MRC Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Addenbrookes Treatment Centre, Cambridge, CB2 0QQ, UK.

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.

KEYWORDS:
Chronic fatigue syndrome; GDF15; Myalgic encephalomyelitis
PMID: 31801546 DOI: 10.1186/s12967-019-02153-6

 

[Sad Dad]

The authors believe GDF15 may be a biomarker, but not a contributing factor for ME/CFS. However, given the number of elite athletes who get CFS, I was struck by the statement, "Secondly, it has also been shown that GDF15 increases following physical activity."

They go on to say, "The receptor for GDF15 is expressed in the brain, where its activation results in a range of responses." I couldn't help thinking about Jared Younger's work when I read this. However, the authors state, "GFRAL, a transmembrane receptor localised to the hindbrain, [is] the putative target for GDF15". I believe Dr. Younger has been seeing increased temperatures in the front of the brain.