Discriminatory cytokine profiles predict muscle function, fatigue and cognitive function in patients with Myalgic Encephalomyelitis/CFS

mitoMAN

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Discriminatory cytokine profiles predict muscle function, fatigue and cognitive function in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Abstract:
https://www.medrxiv.org/content/10.1101/2020.08.17.20164715v1

Full paper:
https://www.medrxiv.org/content/10.1101/2020.08.17.20164715v1.full.pdf

Abstract
Myalgic Encephalomyelitis (ME) /Chronic Fatigue Syndrome (CFS) is a severely debilitating and complex illness of uncertain aetiology, affecting the lives of millions and characterised by prolonged fatigue. The initiating factors and mechanisms leading to chronic debilitating muscle fatigue in ME/CFS are unknown and are complicated by the time required for diagnosis. Both mitochondrial dysfunction and inflammation have been proposed to be central to the pathogenesis of ME/CFS. This original and extensive study demonstrated that although there was little dysfunction evident in the muscle mitochondria of patients with ME/CFS, particular blood plasma and skeletal muscle cytokines, when adjusted for age, gender and cytokine interactions could predict both diagnosis and a number of measures common to patients with ME/CFS. These included MVC and perceived fatigue as well as cognitive indices such as pattern and verbal reaction times. We employed advanced multivariate analyses to cytokine profiles that leverages covariation and intrinsic redundancy to identify patterns of immune signaling that can be evaluated for their predictions of disease phenotype. The current study identified discriminatory cytokine profiles that can be sufficiently used to distinguish HCs from patients with ME/CFS and provides compelling evidence that a limited number of cytokines are associated with diagnosis and fatigue. Moreover, this study demonstrates significant potential of using multiplex cytokine profiles and bioinformatics as diagnostic tools for ME/CFS, potentiating the possibility of not only diagnosis, but also being able to individually personalise therapies.



Personal selection of outtakes:
The association of plasma cytokines with diagnosis and symptoms of ME: .... diagnosis of ME/CFS is significantly associated with increased plasma content of IL-10, MIP-1β, and RANTES and lower PDGF, IL-6, eotaxin, MIP-1α and VEGF. ...... higher plasma values of IL-1β, IL-8, IL-10, IP-10, and RANTES were significantly associated with higher Chalder Fatigue scores i.e. greater perceived fatigue"

Dysfunctional mitochondria have been reported in non-muscle cells from patients with ME/CFS (eg (28)) and so although the current study suggests that there are no major mitochondrial abnormalities in skeletal muscle mitochondria, it does not rule out the potential role of dysfunctional non-muscle mitochondria.

The source of plasma cytokines in patients with ME/CFS are unclear, but a number of cytokines can be produced by muscle (75-78). Studies have shown that the acute release of cytokines by muscle during exercise, a process which is quickly resolved, is likely to contribute to the positive effects of activity (78). In contrast, a chronic release of pro-inflammatory cytokines will undoubtedly have a detrimental effect on both muscle and non-muscle organs including the brain, and such cross-tissue interactions have been relatively well described during ageing (77). The specific increased production of IP-10 and MCP-1 by muscle is likely to have an effect on local tissue such as the peripheral nerve. This is supported by studies in inflammatory demyelinating neuropathies which imply a pathogenic role for IP-10 in the genesis of these neuropathies (79).




Myself:
I am moderate-severe (can still leave the flat for around 20mins per day and go for a very slow walk) and have very high IL-1B, IL-8, TGF-B and borderline maximum IL-10. IP-10 is in range. Never checked RANTES tho.
My IL-6 is low as suggested by the study.


Their Cytokine profile seems to be matching my personal CFS profile pretty well.
Sadly some of the markers are not possible to be checked privately in Germany:
MIP-1B - MIP-1a, eotaxin, PDGF, G-CSF.
 
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Diwi9

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I haven't been tested for cytokine levels, but my VEGF was very high when I was tested in 2017, which is contradictory to this study.
 

Wishful

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The findings fits my understanding of ME: that it's not a muscle disorder, but does involve abnormalities in the immune systems. I like that they don't rule out mito dysfunction in brain cells being involved.

I can't find my cytokine profile at the moment, but I do recall that RANTES, eotaxin, and MIP-1alpha were elevated. None were significantly low.
 

Learner1

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IL 1b, IL 6,:and IL 10 are never high for me. This test showed a clear autoimmune profile Even though I still had infections at this point. But this is what made me go after the treatments for autoimmunity so hard.

Screenshot_20200901-074947.png

Cytokines vary over time, they are not static. They are little communication chemicals that the immune system uses. I have also tried capturing cytokines before and after exercise, because they apparently change then, but I was unable to get the lab to do the test fast enough after my exercise to catch them.
 

mitoMAN

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Would love to read more lab tested values of CFS Patients from this forum.

I am going to have VEGF, BDNF and Rantes tested in a month to compare.

Sadly I dont have the option to test MIP-1B - MIP-1a, eotaxin, PDGF, G-CSF.
 

sometexan84

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I just have crazy high IL-10.

I really really hate the CytoDx test showing "<dl".. so I can't see how low some of the levels actually are.

I'd love to have more cytokine testing options available.

1612321379386.png
 
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These studies are all to be enjoyed with caution. I also showed my cytokines to a Davis-research-team-member, and she said it was not always possible to derive something from individual values. the immune system is constantly changing, so you need to repeat the test several times over time.
However, I have to say that if the value goes through the roof that should mean something! But I myself have extreme values in some tests and then normal again in the following test; same lab, good lab, just a few months later. therefore, these immunoassays are often not much better than microbiome tests.
But that's just my conclusion.
But of course, that doesn’t goes for a study where subjects have the same anomalies... I only mean individual tests
 
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Learner1

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I used the CytoDX as well. It was extremely helpful to me as I had several cytokines pointing strongly to autoimmunity and none for infections, which I'd been treating, which gave me some confidence to try Rituximab in addition to high dose IVIG, which have helped.

I also used the CellTrend POTS panel which showed high antibodies.

@mitoMAN Before you go spending gobs of money on SS-31, looks like these problems might be worth tackling. I wasted a lot of money before I found that treating infections and autoimmunity were essential before fixing my mitochondria.
 
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Sadly some of the markers are not possible to be checked privately in Germany:
MIP-1B - MIP-1a, eotaxin, PDGF, G-CSF.
Redlabs Belgium offers MIP-1B (part of panel) along with the alarmin IL-33. The latter can induce selective release of IL-8 and VEGF from mast cells, you got them both elevated. CRH can do that as well.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003574/table/T4/

https://drive.google.com/file/d/1YBnZhO7yWYWHf17H23SimWHUOTzD_DA-/view

I also used the CellTrend POTS panel which showed high antibodies.
Which ones were elevated?
 
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mitoMAN

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@mitoMAN Mast cells can release IL-1ra, VEGF and RANTES as well. High VEGF could mean increased permeability of the BBB and vascular endothelium. Immune cells may leak into the brain causing inflammation via microglia. What type of antibody against the coxsackievirus is that? IgG? Viral infection may also upregulate VEGF.

VEGF Upregulation in Viral Infections and Its Possible Therapeutic Implications

This is gold! Thank you for posting.
The titers are the Neutralization Testing for Coxsackie Viruses (NIT)
The Titers were high even two months apart. While usually they should only be that high for a few days or weeks in a row.

However I also have MCAS! So that might make sense why my VEGF and RANTES are so high. Inlcuding IL-1B.

Sadly none of the standard treatments have helped me so far. (MCAS)


Do you have suggetsions on how to lower these markers?