Cytokine signatures in chronic fatigue syndrome patients (2017) Roerink

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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.

https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-017-1371-9
 
Interesting quote:

IL-12b, also known as IL-12p40, was significantly higher in CFS/ME patients compared to healthy controls (p = 0.005). The IL-12p40 subunit is expressed by activated dendritic cells (DC) and combines with either subunit p35 or p19, to form IL-12 or IL-23 [37]. IL-12 targets T-cells and NK-cells, in which it induces IFN-γ production [38]. IL-23 has an important role in Th17 production, has an effect on memory T-cells, and appears to be critical in cerebral autoimmune inflammation [39].
 
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.

https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-017-1371-9
The authors are
Megan E. Roerink, Hans Knoop, Ewald M. Bronkhorst, Henk A. Mouthaan, Luuk J. A. C. Hawinkels, Leo A. B. Joosten and Jos W. M. van der Meer

Journal of Translational Medicine 2017 15:267

https://doi.org/10.1186/s12967-017-1371-9

© The Author(s) 2017

Received: 20 October 2017

Accepted: 18 December 2017

Published: 29 December 2017

Knoop has an interesting collection of articles, from the absurd to the credible.
 
Interesting quote:

IL-12b, also known as IL-12p40, was significantly higher in CFS/ME patients compared to healthy controls (p = 0.005). The IL-12p40 subunit is expressed by activated dendritic cells (DC) and combines with either subunit p35 or p19, to form IL-12 or IL-23 [37]. IL-12 targets T-cells and NK-cells, in which it induces IFN-γ production [38]. IL-23 has an important role in Th17 production, has an effect on memory T-cells, and appears to be critical in cerebral autoimmune inflammation [39].
IL-12 therapy is also used in non-Hodgkin T-cell Lymphoma, which my sibling died of in her mid 20s.

https://www.researchgate.net/public...eukin-12_Therapy_of_Cutaneous_T_Cell_Lymphoma

Also, IL-12 has been implicated in insulin-dependent Type 1 diabetes mellitus , which one of my parents suffered from.

https://www.researchgate.net/publication/12154344_Interleukin_12_and_autoimmune_diabetes

Coincidence?
 
In the 2015 Columbia paper, IL-12p40 showed very significant differences between controls and both long- and short-term patients (DN p=0.0012 and UP p= 0.0009. respectively) and between the two patient subsets themselves (p<0.0001).

The finding was far less significant when short- and long-term patients were combined and measured against controls (DN p=0.0803).


http://advances.sciencemag.org/content/1/1/e1400121
 
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