Research news from Bhupesh Prusty

[Hutan]

So, if I'm reading that right, fibronectin is the biomarker? And he's saying that women naturally have higher levels, so a smaller perturbation in women can raise fibronectin levels to a problematic level.

And that an infection like covid-19 reactivates HSV-6 and the herpes virus helps to squash the covid-19 infection. So, there's an evolutionary advantage, a survival benefit, to the reactivation, but also it creates the risk of the ME/CFS.

 

[Hutan]

International ME/CFS Conference of the Charité Fatigue Center on 11./12. May 2023 in Berlin, supported by the ME/CFS Research Foundation
Check out @chillier's good post for Prusty's chart of fibronectin levels.

 

[Solstice]

So, if I'm reading that right, fibronectin is the biomarker? And he's saying that women naturally have higher levels, so a smaller perturbation in women can raise fibronectin levels to a problematic level.

And that an infection like covid-19 reactivates HSV-6 and the herpes virus helps to squash the covid-19 infection. So, there's an evolutionary advantage, a survival benefit, to the reactivation, but also it creates the risk of the ME/CFS.

Tess Falor (Ale Frost), Ph.D. | @RemissionBiome
@tessfalor
12h

If there is autoimmunity playing a role, can we divide group based on what autoantibody? Looked into 120 different IgG and IgM in different types of autoimmune and 120 different pathogen IgG and IgM IgG response didn't divide patients. Random

Tess Falor (Ale Frost), Ph.D. | @RemissionBiome
@tessfalor
·
12h

IgM separated into 3 different groups (severe, control, and mild #MECFS) antibody against CRP very high in #MECFS IgM response against fibronectin depleted in severe ME

I think those are the two most relevant tweets but you need the rest for context. I don't think it says fibronectin is the biomarker but rather that the IgM response against fibronectin is depleted/absent. But maybe that means the same thing? This stuff is beyond me most of the time tbh, so I don't even know if I've got the two most relevant tweets.

 

[Solstice]

This one is worth reading through too. About the same talk.

 

[Andy]

This person with LC on Twitter has summarised the recent podcast with Prusty where his theory was discussed.

 

[Trish]

I think I'll wait until the paper is published and there's some expert commentary on it. All these snippets of information are enticing, but for me with my limited knowledge, I feel none the wiser.

And there are other questions on how secure this information is. For example, how many pwME and pwLC were tested and how many controls, both healthy and with other conditions? Is anyone from another lab working on replication?

 

[Jonathan Edwards]

I haven't read anything so far that means much so I am none the wiser either.

Fibronectin is the molecular that sticks to anything, so the perfect candidate for giving spurious results.

 

[SNT Gatchaman]

and how many controls, both healthy and with other conditions?

The other conditions part would seem particularly important if "low natural IgM -> increased fibronectin" is being proposed as a specific disease biomarker.

 

[Ravn]

Long podcast 1h14. Does help make the tweets about Prusty's IiMC talk a little more comprehensible.Interesting listen but above my pay grade to judge

See comments below the podcast for a reasonable summary. I think there might be some confusion between mito hypofusion and hyperfusion though. The comment has it as hypo, tweets from the IIMC conference had it as hyper. I listened and can't make out what he says but he talks about mitos clumping together which would point to hyperfusion (this has something to do with dUTPase and herpes). But later he talks about mito fragmentation (something to do with IgG)

And I've pretty much forgotten everything else. ME brain...

https://www.tlcsessions.net/episodes/episode-58-breakthrough-biomarker-

 

[Arvo]

I'm currently watching Prusty's talk at Charité (blown away, so interesting!! And I find him a good speaker), and there he says FN1 is not a biomarker. So is he really saying it now?

"Now this is definitely nòt a very prominent biomarker because you can see the something-something score is roughly around 67, but what is very interesting is that if you measure the fibronectin amount in the serum you can actually correlate with the disease severity." - 15.40 conference video

Edited to add link to Bhupesh Prusty's Charité conference video for easy finding: ME/CFS Conference 2023 – ME/CFS Research Foundation (mecfs-research.org)

 

[AknaMontes]

Sad that IVIG seems to be his suggested treatment, as it is impossibly expensive for almost everyone and I cannot imagine the NHS managing to provide it for even a tiny number of those in the UK with ME and LC.

 

[SNT Gatchaman]

there he says FN1 is not a biomarker. So is he really saying it now?

I think he's saying the biomarker is the natural IgM that forms an immune complex with FN1 (reducing its freely bioactive fraction?). A little hard to judge until the preprint available. I'm unclear on how it ties in to the herpesvirus dUTPases and DRP1 in relation to mitochondrial hyperpolarisation (which as Ravn noted are sometimes indicated as either hyper -fission or -fusion). I understood that he suspected the marrow B1 plasma cell that was responsible for producing this natural IgM may be infected with a latent virus, whose early activation profile was leading to reduction in IgM - but that this was yet to be evaluated.

Someone had posted a reference to The importance of natural IgM: scavenger, protector and regulator (2010, Nature Reviews Immunology) which is paywalled, but is - ahem - cached, elsewhere. I haven't yet read to see if this is helpful in understanding natural IgM and there may be a more recent review.

 

[FMMM1]

Apologies only scanned a few posts above but my reaction is that it sums up why @Jonathan identified/supported GWAS i.e since it may/should help to identify where research should focus. Also, Jonathan's comments that recent advances in medicine have been via genetics --
No disrespect intended but we could be p-----g around for ages with hypothesis drive research --- focus via GWAS is badly needed.

 

[Solstice]

Sad that IVIG seems to be his suggested treatment, as it is impossibly expensive for almost everyone and I cannot imagine the NHS managing to provide it for even a tiny number of those in the UK with ME and LC.

He says there's a lot of uncertainties about IVIG but it could be something worth looking into.

 

[FMMM1]

Sad that IVIG seems to be his suggested treatment, as it is impossibly expensive for almost everyone and I cannot imagine the NHS managing to provide it for even a tiny number of those in the UK with ME and LC.

I'd like to see some evidence -- trials i.e. supporting its use.

 

[Hoopoe]

I'm trying to catch up with Prusty's ideas at the moment and it's hard to follow and understand. It will be easier once the paper is published.

A key idea seems to be that fibronectin is not being integrated into immune complexes (complement?), and that natural IgM is low.

@Jonathan Edwards do you know what he means?

 

[Jonathan Edwards]

The whole thing seems to me to be an immunobabble word salad based on nothing I am afraid. What we need is hard facts, not tired old theories put into a shaker and thrown out again.

 

[Hoopoe]

Ouch, Brutal.

 

[dreampop]

One question I had at the start, was there a need to "get this out there" on twitter and naturally generate social media hype. I think the answer to that is pretty uniformly "no" and in retrospect does not benefit the me/cfs community. I think that colors the situation quite badly.

 

[Perrier]

Sad that IVIG seems to be his suggested treatment, as it is impossibly expensive for almost everyone and I cannot imagine the NHS managing to provide it for even a tiny number of those in the UK with ME and LC.

My daughter tried IVIG and it did not alter things: after several infusions, her mouth swelled, tongue swelled, and Benadryl IV had to be administered. Another doctor later said not to try it again.