Cytokine Expression Profiles in Post Mono CFS

[shannah]

Cytokine expression profiles of immune imbalance in post-mononucleosis chronic fatigue

Gordon Broderick, Ben Z Katz, Henrique Fernandes, Mary Ann Fletcher, Nancy G Klimas, Frederick A Smith, Maurice RG O'Gorman, Suzanne D Vernon and Renee Taylor

Journal of Translational Medicine 2012, 10:191 doi:10.1186/1479-5876-10-191
Published: 13 September 2012
Abstract (provisional)

Background

As Chronic Fatigue Syndrome (CFS) has been known to follow Epstein-Bar virus (EBV) and other systemic infections; our objective was to describe differences in immune activation in post-infective CFS (PI-CFS) patients and recovered controls. We studied 301 adolescents prospectively over 24 months following the diagnosis of monospot-positive infectious mononucleosis (IM). We found an incidence of CFS at 6, 12 and 24 months of 13%, 7% and 4% respectively.
Methods

Using chemiluminescent imaging we measured the concentrations of IL-1a, 1b, 2, 4, 5, 6, 8, 10, 12 (p70), 13, 15, 17 and 23, IFN-gamma, TNF-alpha and TNF-beta in duplicate plasma samples available in bio-bank from 9 PI-CFS subjects and 12 recovered controls at 24 months post-infection.
Results

Standard comparative analysis indicated significant differences in IL-8 and 23 across subject groups. In constructing a linear classification model IL-6, 8 and 23 were selected by two different statistical approaches as discriminating features, with IL-1a, IL-2 and IFN-gamma also selected in one model or the other. This supported an assignment accuracy of better than 80% at a confidence level of 0.95 into PI-CFS versus recovered controls.
Conclusion

These results suggest that co-expression patterns in as few as 5 cytokines associated with Th17 function may hold promise as a tool for the diagnosis of post-infectious CFS.

http://www.translational-medicine.com/content/10/1/191/abstract

 

[August59]

Good find! Thanks Shannah

 

[WillowJ]

so what's Th17?
http://www.ebioscience.com/knowledge-center/cell-type/th17-cells.htm

Functionally, Th17 cells play a role in host defense against extracellular pathogens by mediating the recruitment of neutrophils and macrophages to infected tissues. ​

Moreover, it has become evident that aberrant regulation of Th17 cells may play a significant role in the pathogenesis of multiple inflammatory and autoimmune disorders.​

 

[mellster]

Spot on - good find!

 

[Snow Leopard]

This is interesting, however the last Broderick study found suppresed Th1/Th17 in favour of Th2. But the difference could be due to the state/progression of the illness.

http://www.ncbi.nlm.nih.gov/pubmed/20447453

But there is also this study:
http://www.ncbi.nlm.nih.gov/pubmed/18774769

Biochem Biophys Res Commun. 2008 Nov 7;376(1):231-3. Epub 2008 Sep 5.
Lower frequency of IL-17F sequence variant (His161Arg) in chronic fatigue syndrome patients.

Metzger K, Frémont M, Roelant C, De Meirleir K.
Source

Protea Biopharma, Z.1-Researchpark 100, 1731 Zellik, Belgium.
Abstract

Chronic fatigue syndrome (CFS) is characterized by immune dysfunctions including chronic immune activation, inflammation, and alteration of cytokine profiles. T helper 17 (Th17) cells belong to a recently identified subset of T helper cells, with crucial regulatory function in inflammatory and autoimmune processes. Th17 cells are implicated in allergic inflammation, intestinal diseases, central nervous system inflammation, disorders that may all contribute to the pathophysiology of CFS. IL-17F is one of the pro-inflammatory cytokines secreted by Th17 cells. We investigated the association between CFS and the frequency of rs763780, a C/T genetic polymorphism leading to His161Arg substitution in the IL-17F protein. The His161Arg variant (C allele) antagonizes the pro-inflammatory effects of the wild-type IL-17F. A significantly lower frequency of the C allele was observed in the CFS population, suggesting that the His161Arg variant may confer protection against the disease. These results suggest a role of Th17 cells in the pathogenesis of CFS.

Also interesting to note that the effect of Rituximab has been correlated a reduction of the Th17 response:
http://www.ncbi.nlm.nih.gov/pubmed/21400475

 

[Enid]

Great research findings - thanks everybody.

And here by Cort if not already in.

 

[roxie60]

This is interesting, however the last Broderick study found suppresed Th1/Th17 in favour of Th2. But the difference could be due to the state/progression of the illness.

http://www.ncbi.nlm.nih.gov/pubmed/20447453

But there is also this study:
http://www.ncbi.nlm.nih.gov/pubmed/18774769


Also interesting to note that the effect of Rituximab has been correlated a reduction of the Th17 response:
http://www.ncbi.nlm.nih.gov/pubmed/21400475

So is this study saying if you have the C alelle that you are less likely to get CFS? I have TT so that is why I'm trying to understand. I looked at SNPedia and it looks like TT is the most common in the population vs CC and CT so that is why I'm confused, would seem to suggest majority of population with TT could have CFS, that cant be correct interpretation...

 

[roxie60]

I also found this research report relating CFS and post Mono

http://www.cfids-cab.org/cfs-inform/Genes/cameron.etal07.pdf

 

[Valentijn]

So is this study saying if you have the C alelle that you are less likely to get CFS? I have TT so that is why I'm trying to understand. I looked at SNPedia and it looks like TT is the most common in the population vs CC and CT so that is why I'm confused, would seem to suggest majority of population with TT could have CFS, that cant be correct interpretation...

Here's the relevant bit:

... the His161Arg variant may confer protection against the disease.

So rather than seeing TT as a risk factor for CFS, they're just saying CC is protective from developing CFS.