Cytokine signatures in chronic fatigue syndrome patients: a Case Control Study and the effect of anakinra treatment.

Abstract

BACKGROUND: Cytokine disturbances have been suggested to be associated with the Chronic Fatigue Syndrome/Myalgic encephalomyelitis (CFS/ME) for decades. METHODS:  Fifty 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. RESULTS: In 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. CONCLUSIONS: In 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.