Circulating levels of GDF15 in patients with myalgic encephalomyelitis/chronic fatigue syndrome, 2019, Melvin, Lacerda, Nacul et al

https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-019-02153-6

eta: can someone explain the conclusions

 

Can't look at the paper at the moment, do they show the mild and moderate results separately anywhere, or are they all lumped into mild/moderate as in the abstract?

 

So there was "no signifcant diferences in GDF15 between ME/CFS cases with mild/moderate disease, MS cases, and healthy volunteers". And they note that
"in rodent models, increases in circulating GDF15 are reported to be associated with reduced physical activity."

Doesn't that suggest that increased GDF15 in severe ME/CFS patients reflect reduced activity and other consequences of the illness rather than the illness itself?

 

It is not clear from the text to me. They say that physical activity leads to increased GDF-15 levels suggesting that activity puts it up. So maybe a high level suppresses further activity as a feedback - that would explain lower activity in rats with high levels.

This seems potentially a very interesting molecule to study. If ME symptoms are mediated by a signalling molecule like this then there is immediately a drug target. If this is a signal that is independent of traditional inflammatory signals then it would make a lot of sense.

 

In children with some mitochondrial diseases, blood levels of this molecule are about 11 times the normal.

Here in ME/CFS they are only slightly higher.

I am not sure but I think this suggests it will not be found to correlate well with symptom severity in ME/CFS.

 

There's been a lot of talk of matching activity level between test group (ME) and control group - MS has been suggested as a control group.

@Jonathan Edwards thoughts on using MS as a control group i.e. in ME studies? Thanks in advance!

 

Fwiw, dude at my dog park has MS and he was involved in a study looking at the effect of exercise - he did not experience PEM when I questioned and explained it - but he did get fitter - his muscles responded well to the workouts.

 

The the UK ME/CFS Biobank strikes again

GDF15 increases with cellular stress.

GDF15 increases with exercise.

GDF15 is elevated in severe ME. Could that be suggestive of permanent cellular stress?

GDF15 is not elevated in mild/moderate ME. Would that change after an exercise challenge? Other studies looking at other markers found no big differences at rest but did find some after applying stressors. I don't think this study included any challenge (only skimmed it), so that would be an interesting next step.

 

(Severe) ME is definitely a mitochondrial disorder, it becomes more and more absurd that nobody is calling it such.

 

I've heard that severe ME looks (metabolically) different from moderate.

 

I don't think the Biobank uses exercise challenges at the moment. They do a hand grip strength test and a 10min standing test, which could cause cellular stress in some patients.

But I don't think this would show up clearly in the results because the first two times I donated to the Biobank there was no standing test, just hand grip, and it was done on a separate occasion from the blood draw (not timed to catch PEM), plus I had taken the bus and walked a bit to the first two blood draws.

For my last donation they came to my house and did the hand grip and stand test immediately before drawing the bloods.

So there aren't controls for exercise or orthostatic stress prior to the blood draw, meaning can't really draw conclusions relating to the impact of physical activity on the blood results.

I think they did this because they don't want to cause PEM. They are very careful (at least in my experience when talking to the nurse who did my blood draw), not to cause any harm to patients, so I don't think they want to intentionally cause PEM (maybe they don't have ethical approval for this).

 

I recently had a consult with my neurologist, and he ordered a GDF-15 test, so I looked it up and found this recent reference.

https://onlinelibrary.wiley.com/doi/10.1002/ana.24506

no paywall.