Discriminatory cytokine profiles predict muscle function, fatigue and cognitive function in patients with ME/CFS. McArdle et al. 2020

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

https://www.medrxiv.org/content/10.1101/2020.08.17.20164715v1?rss=1

This was a study I took part in.

Papers from the same study.
https://bmjopen.bmj.com/content/bmjopen/7/11/e015296.full.pdf
https://faseb.onlinelibrary.wiley.com/doi/abs/10.1096/fasebj.31.1_supplement.lb789

 

Threads for those links.

Existing thread, Vitamin D status in chronic fatigue syndrome/myalgic encephalomyelitis: a cohort study from the North-West of England

New thread, The role of IP‐10 in Chronic Fatigue Syndrome, 2018, McArdle et al

 

I'm very foggy at present, so don't know if this is relevant, but:

"Healthy cells with ME/CFS plasma behave like patient samples, while ME/CFS cells with healthy plasma behave like healthy controls i.e. no increase in impedance."

From https://www.s4me.info/threads/ronal...tation-at-the-iimec13.5793/page-2#post-105495

 

This is one of the set of studies the Medical Research Council funded in 2012, basically the first time the MRC had funded biomedical research. The ME Association also added in a little money for a study that was part of the project.

 

The problem with statistical models like this is that they don't tend to replicate.

The sample size was decent, but 92 male patients and 63 female patients seems like an odd ratio.

On the neuropsychological/cognitive testing, patients had the usual poor reaction times and poorer verbal memory, suggesting poor concentration.

Maximal voluntary contraction was lower in patients than controls, there was no difference in the generation of maximal involuntary contraction by electrical stimulation between the two groups overall and at any frequency (relative to MVC). Given that this is relative to MVC, this is expected, it simply suggests that patients were producing sufficient maximal effort.

Notably, during the "fatigue resistance test" the amplitude of electrical stimulation was not set at supramaximal levels. Instead set at "30% of the participants MVC force when stimulated at 100Hz".

Looking at the graph, it is indeed curious that it was not statistically different. Given that the two seem to deviate further over time, it is possible that a difference would have emerged if the test went on longer than 2 minutes.

Also note that fatigue during similar tests in muscular dystrophies and peripheral neuropathies have the same results, namely the fatigue is predominantly "central" in origin. The fact that the same pattern is observed in vastly different pathologies suggests that there is substantial coupling between peripheral afferents and "central fatigue", likely mediated through spinal feedback of type 3 and type 4 afferents, the purpose of which is to reduce the rate of unexpected peripheral fatigue (and thus makes force output more predictable to the brain).

https://repository.ubn.ru.nl/bitstream/handle/2066/50860/50860.pdf (2006 thesis by Joke Kalkman. Studies compared fatigue in myotonic dystrophy, facioscapulohumeral dystrophy, and Hereditary Motor and Sensory Neuropathy type I - patients had less peripheral fatigue than health controls)

 

Just a small typo, there were 29 male patients.

 

"in situ"

"permeabilization with saponin"

news to me that pwme have surfactants surrounding their muscles! .... (sarcasm )

 

Thought I would quote the abstract of Micheal VanElzakkers paper "Neuroinflammation and Cytokines in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Critical Review of Research Methods"

Paper : https://www.frontiersin.org/articles/10.3389/fneur.2018.01033/full
Thread : https://www.s4me.info/threads/front...-methods-michael-vanelzakker-et-al-2018.6758/

I tried to scan the paper of this thread a few times but could find no detailed description of when they took the blood and how exactly it was processed. Did they use the same equipment and operators for patients and controls and were samples processed together. Montoya went to great lengths in his study to try and even control for centrifuge by alternating samples in slots of the machine.

In Montoya's large Cytokine study paper the "Cytokine Assay" section describes the lengths he went to to ensure good quality. The "Statistical Analysis" section talks about techniques to remove plate effects.

Paper : Cytokine signature associated with disease severity in chronic fatigue syndrome patients
https://www.pnas.org/content/114/34/E7150

"Cytokine Assay" section

"Statistical Analysis" section

 

Can somebody explain figure 2B and the text relating to it?

So the text says no significant difference in muscle fibre generated mitochondrial superoxide, neither with nor without addition of a nitric oxide synthetase inhibitor. Yet the graphs seem to show a difference. Figure 2B shows complete separation of ME from HC from the 40 minute mark, with the trend suggesting even further separation with more time. So why is this not significant?

 

It is certainly confusing. I had to double check Table 1 to confirm that you were right!

The error bars don't suggest statistical significance. The lack of significance is likely due to lack of sample-size and within-group variability.

 

Do we know the ratio of male / females tested?
Asking as some studies have suggested that females utilize protein differently - might this not affect muscles and perhaps indicate catabolization ?

 

It doesn't say what the ratio is, unfortunately.

Given that this is a pre-print, some things can be updated if we are able to notify the authors!

 

Comments can be left on the pre-print itself, and it also picks up tweets that mention the pre-print somehow.