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dc.contributor.authorMelvin, A.
dc.contributor.authorLacerda, E.
dc.contributor.authorDockrell, H. M.
dc.contributor.authorO’Rahilly, S.
dc.contributor.authorNacul, L.
dc.date.accessioned2020-12-03T16:28:23Z
dc.date.available2020-12-03T16:28:23Z
dc.date.issued2019-12-04
dc.date.submitted2019-08-06
dc.identifier.others12967-019-02153-6
dc.identifier.other2153
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/314458
dc.description.abstractAbstract: 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.
dc.languageen
dc.publisherBioMed Central
dc.rightsAttribution 4.0 International (CC BY 4.0)en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectResearch
dc.subjectIllnesses of Unknown Etiology
dc.subjectGDF15
dc.subjectMyalgic encephalomyelitis
dc.subjectChronic fatigue syndrome
dc.titleCirculating levels of GDF15 in patients with myalgic encephalomyelitis/chronic fatigue syndrome
dc.typeArticle
dc.date.updated2020-12-03T16:28:22Z
prism.issueIdentifier1
prism.publicationNameJournal of Translational Medicine
prism.volume17
dc.identifier.doi10.17863/CAM.61562
dcterms.dateAccepted2019-11-22
rioxxterms.versionofrecord10.1186/s12967-019-02153-6
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidMelvin, A. [0000-0002-9582-8454]
dc.identifier.eissn1479-5876
pubs.funder-project-idWellcome Trust (WT 214274/Z/18/Z)
pubs.funder-project-idMedical Research Council (MRC_MC_UU_12012.1)
pubs.funder-project-idNational Institute of Allergy and Infectious Diseases (R01AI103629)
pubs.funder-project-idME Association (PF8947_ME Association)


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Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's licence is described as Attribution 4.0 International (CC BY 4.0)