Abstract
BackgroundCytokine disturbances have been suggested to be associated with the Chronic Fatigue Syndrome/Myalgic encephalomyelitis (CFS/ME) for decades.MethodsFifty female CFS patients were included in a study on the effect of the interleukin-1-receptor antagonist anakinra or placebo during 4 weeks. EDTA plasma was collected from patients before and directly after treatment. At baseline, plasma samples were collected at the same time from 48 healthy, age-matched female neighborhood controls. A panel of 92 inflammatory markers was determined in parallel in 1 μL samples using a ‘proximity extension assay’ (PEA) based immunoassay. Since Transforming growth factor beta (TGF-β) and interleukin-1 receptor antagonist (IL-1Ra) were not included in this platform, these cytokines were measured with ELISA.ResultsIn CFS/ME patients, the ‘normalized protein expression’ value of IL-12p40 and CSF-1 was significantly higher (p value 0.0042 and 0.049, respectively). Furthermore, using LASSO regression, a combination of 47 markers yielded a prediction model with a corrected AUC of 0.73. After correction for multiple testing, anakinra had no effect on circulating cytokines. TGF-β did not differ between patients and controls.ConclusionsIn conclusion, this study demonstrated increased IL-12p40 and CSF-1 concentrations in CFS/ME patients in addition to a set of predictive biomarkers. There was no effect of anakinra on circulating cytokines other than IL-1Ra.Trial Registration: ClinicalTrials.gov Identifier: NCT02108210, Registered April 2014
Highlights
Cytokine disturbances have been suggested to be associated with the Chronic Fatigue Syndrome/ Myalgic encephalomyelitis (CFS/ME) for decades
Chronic fatigue syndrome/Myalgic encephalomyelitis (CFS/ME) is a condition of unknown origin that is characterized by severe fatigue for more than 6 months leading to significant disability
Patient characteristics A total of 50 CFS/ME patients and 48 age-matched, neighborhood controls were included in the study
Summary
Cytokine disturbances have been suggested to be associated with the Chronic Fatigue Syndrome/ Myalgic encephalomyelitis (CFS/ME) for decades. Most of the current case definitions suggest a collection of mandatory diagnostics to exclude common causes for fatigue such as anemia and thyroid illnesses [1, 4], but there is a need for more specific tests to diagnose patients. Another advantage of such a test is that it might be easier to define CFS/ME subgroups [5], for example those patients that would or would not respond to an immune intervention. A distinctive marker or set of markers may point to relevant pathogenetic mechanisms that can be further explored
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