In-Depth Analysis of the Plasma Proteome in ME/CFS Exposes Disrupted Ephrin-Eph and Immune System Signaling, 2021, Hanson et al

I still have my doubts about this because most of these studies were really small. Not sure if these results will hold up in a proper study with a pre-specified protocol, large sample size, adequate control groups etc.

 

One ancient method of diagnosing diabetes was to test whether ants were drawn to the urine of the patient.

In ME/CFS we're still not much further ahead than this it seems. Make patient exercise, if they get worse it's ME/CFS.

 

I'd never even heard of this technique
"To gain insights into the molecular disruptions in ME/CFS, we utilized an aptamer-based technology that quantified 4790 unique human proteins, allowing us to obtain the largest proteomics dataset yet available for this disease, detecting highly abundant proteins as well as rare proteins over a nine-log dynamic range."

Firstly they've analysed more proteins - so more likely to find something. Not sure how low the concentrations for "Ephrin-Eph" were but it may have been lower than other (previously used) conventional methods. Also, I recall a caveat that the other protein studies relied on sample preparation which "lost" some of the proteins. So there may be important differences in this study.

In terms of something being readily observable in blood, Ron Davis pointed out that at least one scientist had a theory that ME was diabetes. In this paper you'll see that "glucose" is a key word here's the first reference to "glucose": "Ephrin-A5 is in the same family as Ephrin-A4 (Table 2) and has been shown to be involved in various biological processes including --- glucose-stimulated insulin secretion through pancreatic islet cell communications.". Check out the other references to glucose - they're all pretty interesting. So in "hindsight" there could potentially be clues in readily observable things in blood in ME.

As the authors suggest we'd need a much bigger study looking in more detail "Ephrin-Eph" e.g. lot more people with ME and people with diseases which have similar presentation - this study used healthy controls*.

People with ME are often dismissed, i.e. labelled as having a psychological rather than a biomedical disease, and thus not warranting biomedical research. This study indicates that the (biomedical) tools are getting better - so biomedical research is justified.

I'm not aware of a good biomedical test which detect Alzheimer's disease at an early (more treatable) stage - perhaps an example of a "worthy" disease which currently doesn't have a good biomarker/diagnostic test.

I'm assuming a study like this would be a prime candidate for funding under Horizon Europe --- perhaps it could include Lyme and Long covid as well as ME & healthy controls.

Anyone in Europe using this technique i.e. aptamer-based technology?

*"We identified nine proteins with individual classifiers greater than 0.85 between ME/CFS subjects and controls as well as nine protein ratios with classifiers above 0.92. As is practice, a diagnostic test for ME/CFS would not be used on subjects who are not complaining of fatigue or malaise; these protein differences must be tested against other fatiguing illness that might be confused with ME/CFS—such as depression, cancer, or chronic Lyme disease, to name a few. Such studies will be needed to determine how the sensitivity and specificity are affected by excluding individuals who do not exhibit fatigue or malaise."
In-Depth Analysis of the Plasma Proteome in ME/CFS Exposes Disrupted Ephrin-Eph and Immune System Signaling

 

I need to look at the data but I think I formed the impression that the group of patients selected demonstrated an issue re Disrupted Ephrin-Eph and Immune System Signaling
If that's correct then perhaps many people with ME have a similar underlying problem --- too early to say though.

 

Aptamers are really cool, I had to study them for my undergraduate degree over 10 years ago.

The key is to have an off-the-shelf kit with validated sensitivity/specificity. (which is not perfect BTW, this is primarily a discovery tool)
The set of aptamers has only been commercially available (with over 4000 targets) since 2017.
https://en.wikipedia.org/wiki/SomaLogic

 

Cornell is also allowing on private donors to fund their work. This study was funded partly by Cornell which I assume is private donors.

https://twitter.com/user/status/1355523208485744646

 

Thank you Snow Leopard.

Vaguely recall a guy in a corner of the lab (30+ years ago!) working on biotin binding ---- not sure that's at all relevant!

I expect that once you've identified compounds of interest then you can determine them using other methods. E.g. if you Google "Ephrin-Eph + mass spectrometry" then you'll see a bunch of stuff (detection methods). That may indicate off the shelf [mass spectrometry] methods to give more accurate measurements of e.g. Ephrin-Eph(?).

Noticed Cornell have applied for a patent - maybe someone could find it.
[6. Patents
A provisional patent application (U.S. Serial No. 63132722) concerning the data has been filed by Cornell University.]

 

I recall this paper which compared Lyme and ME [https://pubmed.ncbi.nlm.nih.gov/21383843/] It's a protein study of Lyme and CFS - data is presented in the way you suggest.

So yea, an update which used this technique Aptamers would seem to be in order --- would it need to be expanded to include Long covid ---? Mind you if you included Lyme and Long covid (as well as ME) then it might be easier to get funding!

 

Patents are horrible to read so I'll pass on that!

I am kind of glad they have patented this as a patent by the wrong people could hold up progress...

As for biotin, it's commonly used in bionanotechnology with Avidin to stick things together.

 

Thanks. I'm laughing here - you obviously understand this much better than I do - which is great.

 

It's occurred to me that this technique [aptamer-based proteomics] is similar to genome-wide association study (GWAS). I.e. you don't know what the cause [of ME] is and you measure everything - in the hope you find something different between people with ME & healthy controls. OK the authors highlight that you then need to look at similar diseases (Lyme etc.).

The MRC panel @Jonathan Edwards sat on identified GWAS as a worthwhile study area* and that led to Chris Ponting's GWAS study being funded. Not sure if the MRC are still using that approach i.e. convene a panel to consider worthwhile research areas - like aptamer-based proteomics!


*https://www.s4me.info/threads/georg...dian-article-21-1-21.18562/page-4#post-319043

 

If proteins related to the cytoskeleton, cell-cell communication, extracellular matrix, etc. keep showing maybe it's time to physically look at cells of patients and the spaces inbetween them. My understanding is that different kinds of ephrins in different tissues which would be a clue as to there the problem could be. Is this possible to do?