What do you think needs to be tested in the blood (plasma, PBMCs, etc) of patients?

We do a number of studies on blood samples, we capture plasma and PBMCs, sometimes we captures serum and RBCs.

What type of markers do you guys think should be looked at? Or what type of assays should be performed on these biomarkers? You can even suggest combinations. Specific names should be used.

Example might be to measure Vasopressin or it could be to capture B cells and measure ATP production when activated. Could be anything but specific is good.

 

Maybe testing the B cell repertoire to try to further replicate or falsify high IGHV3-30? (Others that might be high as well from other studies were IGHV3-23 and IGHV3-30-3.) Maybe other antibody signals might appear as well.

 

From Ingrid Rekeland’s dissertation on the cyclophosphamide trial and from recent data from the Daratumumab trial it appears that patients with high IGG levels don’t respond to treatment(s), more data collection/deeper dive on this would probably be useful.

https://www.s4me.info/threads/myalg...nd-pathomechanisms-2024-rekeland.38262/page-3

https://www.s4me.info/threads/pilot-study-in-norway-daratumumab-in-me-cfs.28098/

 

I think hypoxanthine is relevant, but it's not easy to test reliably. Elevated values, I think might be a very strong indicator (but not a diagnostic biomarker due to a lack of specificity) for having ME.

 

In general I would shift to sorted cell studies. The 'PBMC' category was always pretty ridiculous because it includes at least four largely unrelated cell types. They might all be affected by a metabolic shift but since cells in blood are by and largely just inactive cells undergoing transportation - for PBMC most have hardly any cytoplasm - I doubt they are a sensible cell group to study to look at that.

 

I’m getting the sense that quite a lot of pwme are getting polycythemia type results - not always picked up because eg it used to be someone with iron deficiency was just tested for the simplest test by GP advice they were being given and not things like ferritin etc. if you didn’t have anemia it didn’t exist. They were being functionally focused to just look at the haemoglobin. I’m not sure that’s changed

of course dehydration can be a cause , and thick blood is common, but plasma is never measured. And someone might drink a lot of liquid yet have indicators of dehydration but sadly the tendency when that crops up is that patient testimony is taught to be disbelieved

I’ve heard you can’t measure plasma , or standard tests don’t to know what is artefacts of tgat (and whether that ‘artefact’ is actually a clue). It might sound off the wall but it would be interesting to see if there are differences in some when they do a blood test with fluid eg thirty mins before vs actually taking fluid during the test given how apparently this affects the scores for some of these. Then maybe see if vasopressin correlates or whatever is relevant.

I’ve looked up the role of ferritin in energy production , and hepcidin, (seeing but not being able to fully interrogate what’s good or not that there are now suggestions of hepcidin being related to an exercise increase with an xhrs delay, potentially ferritin plays a part in skeletal muscle, neurons/crossing BBB) as was interested by this, but with little expertise it’s hard to work out what would be downstream upstream etc but was fascinated

 

Complement factor H was high in the Ponting UK Biobank study, CFH gene was significant in another ME/CFS study, and it has been high in several long COVID studies and in some potentially related conditions (MS and fibromyalgia). Maybe multiple parts of the complement system could be tested, including some of the other findings from one of the LC studies, Cervia-Hasler 2024, such as "patients showed imbalanced TCC formation, marked by increased soluble C5bC6 complexes and decreased levels of C7-containing TCC formations that can incorporate into cell membranes."

 

I would like for a research group to test for glycosylation disruption.

So Transferrin Isoform Analysis, N-Glycan profiling, Dolichol Phosphate and Lipid-linked Oligosaccharides

 

Yep, and the only way you can do this is to ask them. Maybe two straightforward questions:

Are you currently experiencing PEM symptoms?

• No
• Yes
• Not sure

In the last two days (including this visit) do you think you've done enough exertion to trigger PEM?

• Probably no
• Probably yes
• Not sure

It's as reliable as anything we have, and most people who've been diagnosed for 18 months or more will have enough experience to answer.

 

I agree about trying to replicate complement H and other complement findings, and hv3-30. I just want to say that I think severe patients should be studied as a priority. We have seen that severe patients may not have the hv3-30 finding and another recent paper found t cell dysregulation or something similar in mild/mod but not severe pwME. So not only do we risk the sickest of us being left behind if they are excluded from research, we may learn valuble things about the disease by including cohorts of them in all studies where it is feasible. Why something might not show up in severe as opposed to mild could tell us more about the disease pathway as a whole.

 

That really, really depends on the doc that diagnosed you. I know people that had a diagnosis for years before they heard of PEM.

But I can’t think of a better set of questions, unless you go for some version of the FUNCAP wording.

 

Blood drawn before, during the 12-14hr window and delayed PEM onset would most likely show something in my case. My experience is distinctive and always follows the same pattern.

I would know exactly how much to overdo to provoke delayed PEM w/o major repercussions.

 

I guess, but it's probably more unusual nowadays? You'd need to be both diagnosed badly and unable to see online information about ME/CFS.

There are folk who can't use or don't have digital devices, of course, and plenty more who're denied open internet access. It seems unlikely to be common in Australians who're plugged into networks well enough to be recruited into studies, but maybe it is worth checking!

 

There’s plenty of missinformation online about ME/CFS. And there are many understandable and valid reasons to seek out cures, treatments or reasons for hope, rather than the bleak «we barely know anything and we don’t know how to make you better».

Keep in mind that the Norwegian National Competency Centre for ME/CFS exclusively promotes Wyller’s research. Why would you question them or other experts like Sir Simon Wessely?

 

I feel like I’m going a bit off topic here, even though the questions are relevant for the sample collection process.

Maybe we should leave it at «try to screen for PEM»? Another thread could be created to delve deeper into the correct questions phrasing.

 

Yep, there’s plenty of groups with BPS moderators who silence any sort of biomedical perspectives.

Ie. r/cfsme and r/mecfs on reddit.

 

I suspected I had 'Cfs' for years but the NHS page was terrible and didn't mention PEM, and doctors were dismissive. I assumed that it just meant I would be tired and ill forever unless it cleared up. I had no idea about delayed PEM or that I could get worse.
The information about PEM and GET harms is not or at least was not pre 2021 obvious. My partner and I both missed it and our lives were destroyed because of it.

Remember doctors encorage you not to google your disease too.

 

1000 times THIS.

If they dont know what PEM is then couldnt they ask & be answered with info, or tick 'not sure'?