Plasma cytokine expression in adolescent chronic fatigue syndrome

[Denise]

Plasma cytokine expression in adolescent chronic fatigue syndrome

• Vegard Bruun Wyllera, b, c, , ,
  
  
• Øystein Sørensend,
  
  
• Dag Sulheima, e,
  
  
• Even Fagermoenf, g,
  
  
• Thor Uelandh, i,
  
  
• Tom Eirik Mollnesj, k, l
  

Highlights
• Chronic fatigue syndrome (CFS) might be related to altered cytokine expression.
• A total of 120 adolescent CFS patients and 68 healthy controls were studied.
• Individual cytokine levels where similar across the two groups.
• Cytokine network parameters (ARACNE algorithm) were similar across the two groups.
• In CFS patients, there were no associations between symptoms and network parameters.
Abstract
Chronic fatigue syndrome (CFS) is a prevalent and disabling condition among adolescents. The pathophysiology is poorly understood, but low-grade systemic inflammation has been suggested as an important component. This study compared circulating levels of individual cytokines and parameters of cytokine networks in a large set of adolescent CFS patients and healthy controls, and explored associations between cytokines and symptoms in the CFS group.

CFS patients (12–18 years old) were recruited nation-wide to a single referral center as part of the NorCAPITAL project (ClinicalTrials ID: NCT01040429). A broad case definition of CFS was applied, requiring three months of unexplained, disabling chronic/relapsing fatigue of new onset, whereas no accompanying symptoms were necessary. Thus, the case definition was broader than the Fukuda-criteria of CFS. Healthy controls having comparable distribution of gender and age were recruited from local schools. Twenty-seven plasma cytokines, including interleukins, chemokines and growth factors were assayed using multiplex technology. The results were subjected to network analyses using the ARACNE algorithm. Symptoms were charted by a questionnaire, and patients were subgrouped according to the Fukuda-criteria.

A total of 120 CFS patients and 68 healthy controls were included. CFS patients had higher scores for fatigue (p < 0.001) and inflammatory symptoms (p < 0.001) than healthy controls. All cytokine levels and cytokine network parameters were similar, and none of the differences were statistically different across the two groups, also when adjusting for adherence to the Fukuda criteria of CFS. Within the CFS group, there were no associations between aggregate cytokine network parameters and symptom scores.

Adolescent CFS patients are burdened by symptoms that might suggest low-grade systemic inflammation, but plasma levels of individual cytokines as well as cytokine network measures were not different from healthy controls, and there were no associations between symptoms and cytokine expression in the CFS group. Low-grade systemic inflammation does not appear to be a central part of adolescent CFS pathophysiology.

Keywords

• Chronic fatigue syndrome;
  
  
• Adolescent;
  
  
• Inflammation;
  
  
• Cytokine
  

Corresponding author at: Dept. of Paediatrics, Akershus University Hospital, N-1478 Lørenskog, Norway. Tel.: +47 91 16 66 81.
Copyright © 2014 Published by Elsevier Inc .

http://www.sciencedirect.com/science/article/pii/S088915911400614X

In this study Wyller is applying a unique (to him?) definition - broader than Fukuda, more like Oxford with 3 months of fatigue as the only symptom required.

 

[deleder2k]

A story about LP and this in todays newspaper VG in Norway.

This is some of the article;

Wyller believes that many that are sick with ME are sick for other reasons than what the patients believe themselves. On Friday his newest study is published in the international recognised journal Brain, Behavior and Immunity. The study suggests that ME is not an autoimmune disease - a disease were the immune system attacks itself.

- ME is not an autoimmune disease

Bruun Wyller says Thomas Overvik illustrates the positive effect of mental training can have some ME patients.


- I'm not saying that people with ME are not sick, but I think it is totally incomprehensible not to include psychology in this debate. I'm not saying that we should exclude biology, but that research must be able to deal with both, says Bruun Wyller VG.


In his new research, he, along with professor and physician at Immunology department at Rikshospitalet Tom Eirik Mollnes compared inflammation markers in 68 healthy and 120 ME sufferers youth.


The conclusion suggests that ME is an inflammatory disease / autoimmune disease.


- There was absolutely no difference in the amount of inflammation markers in ME sick and healthy adolescents, says Bruun Wyller VG.


Strife in research

It has long been controversy in research about how best ME should be treated and defined.


While Rikshospitalet believe that ME should be treated with mental training, called cognitive therapy, researchers from Haukeland University Hospital in Bergen, have a biomedical approach to ME. They work partly on the basis of the theory that ME is an autoimmune disease.


- If the ME had been an autoimmune disease, where inflammation is the main problem we had almost certainly found differences. This is another result that supports our view in ME debate, says Bruun Wyller.


- The research excludes nothing

Consultant at the Department of Oncology at Haukeland Hospital, Øystein Fluge, says he will read the article by Bruun Wyller with interest. He does not want the two research groups will emerge as polarities to each other, although the focus and hypothesis for ME is different.


He stressed that researchers at Haukeland have not proved that ME is an autoimmune disease, but says that there are several factors that indicate that this is true.


- Lack of inflammatory changes in blood samples does not preclude that autoimmunity may be involved, says Fluge.


- Although we Haukeland researching ME on the basis that it is a variant of an autoimmune disease, it is important that research in several areas until we find the final answer says Fluge.


- We must also take the consequences of the results we arrive at, and change course if the results from the research shows that it is correct.

The doctor says that they at Haukeland Hospital constantly working to confirm or disprove his hypothesis. In a newly founded study, the hospital following a large group of patients for two years.


- This study will hopefully provide a clarification, he says.

@Jonathan Edwards, I guess you agree with Fluge on this? When Wyller is speaking about inflammation, I guess he is referring to CRP? Isn't there a lot of autoimmune diseases with low or no changes in CRP?

 

[deleder2k]

This is a similar study which came to a different conclusion:

Cytokine expression provides clues to the pathophysiology of Gulf War illness and myalgic encephalomyelitis.

Gulf War illness (GWI) is a chronic disease of unknown etiology characterized by persistent symptoms such as cognitive impairment, unexplained fatigue, pervasive pain, headaches, and gastrointestinal abnormalities. Current reports suggest that as many as 200,000 veterans who served in the 1990-1991 Persian Gulf War were afflicted. Several potential triggers of GWI have been proposed including chemical exposure, toxins, vaccines, and unknown infectious agents. However, a definitive cause of GWI has not been identified and a specific biological marker that can consistently delineate the disease has not been defined. Myalgic encephalomyelitis (ME) is a disease with similar and overlapping symptomology, and subjects diagnosed with GWI typically fit the diagnostic criteria for ME. For these reasons, GWI is often considered a subgroup of ME. To explore this possibility and identify immune parameters that may help to understand GWI pathophysiology, we measured 77 serum cytokines in subjects with GWI and compared these data to that of subjects with ME as well as healthy controls. Our analysis identified a group of cytokines that identified ME and GWI cases with sensitivities of 92.5% and 64.9%, respectively. The five most significant cytokines in decreasing order of importance were IL-7, IL-4, TNF-α, IL-13, and IL-17F. When delineating GWI and ME cases from healthy controls, the observed specificity was only 33.3%, suggesting that with respect to cytokineexpression, GWI cases resemble control subjects to a greater extent than ME cases across a number of parameters. These results imply that serum cytokines are representative of ME pathology to a greater extent than GWI and further suggest that the two diseases have distinct immune profiles despite their overlapping symptomology.

http://www.ncbi.nlm.nih.gov/pubmed/25514671

 

[Jonathan Edwards]

A story about LP and this in todays newspaper VG in Norway.

@Jonathan Edwards, I guess you agree with Fluge on this? When Wyller is speaking about inflammation, I guess he is referring to CRP? Isn't there a lot of autoimmune diseases with low or no changes in CRP?

Lots of autoimmune processes produce no inflammatory signs. I think somebody needs to do a bit of homework from basic medical textbooks. There is only inflammation if the effector mechanism whereby the antibody causes disease also triggers inflammatory mediator relase. There are several mechanisms where this does occur but scores of other mechanisms where it does not. Unfortunately immunology tends not to be a strong point with physicians - even with rheumatologists!