Preprint A Proposed Mechanism for ME/CFS Invoking Macrophage Fc-gamma-RI and Interferon Gamma, 2025, Edwards, Cambridge and Cliff

rapidboson said:
Yes, from what I've seen - and I haven't looked into it too deeply - it did seem to broadly affect lymphocyte proliferation. And was just wondering how, based on your hypothesis and isoprinosine's mechanism of action, you'd expect this to affect pwME.
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I would guess it would do nothing because any general leaning on lymphocytes to do a bit more of this is likely to immediately get offset by mechanisms to ensure a bit more of the other. If you poison lymphocytes in people with RA a bit, mostly nothing happens. You need to interfere in a very precise way. My guess is that ME/CFS will be the same. You will need to interfere in a precise way in the a specific pathway.

And there will be hundreds of people who have ME/CFS or Long Covid who have been exposed to these agents and we don't hear of many miracle cures.
 
Jonathan Edwards said:
I would guess it would do nothing because any general leaning on lymphocytes to do a bit more of this is likely to immediately get offset by mechanisms to ensure a bit more of the other. If you poison lymphocytes in people with RA a bit, mostly nothing happens. You need to interfere in a very precise way. My guess is that ME/CFS will be the same. You will need to interfere in a precise way in the a specific pathway.
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Very interesting, thank you!

Jonathan Edwards said:
we don't hear of many miracle cures.
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Oh, I didn't want to imply that this could be a miracle cure. Just trying to wrap my head around potential consequences. E.g. as gamma IFN had been found increased in some studies. If I understand your hypothesis correctly, this would/should promote the vicious cycle you describe. But I suppose it's much more complex.
 
The paper has been viewed over 8,000 times and downloaded over 1,200 times now, and it's occurred to me to wonder who has been reading it. The ME/CFS field of researchers is tiny. Do we think the paper has pulled in a far wider audience of scientists, or is it likely that most of the interest is coming from interested PwME?
 
I suspect not many in the ME/CFS field have the expertise to comment on the hypothesis itself. They'd be picking at the descriptions, the epidemiology, etc.

Which isn't irrelevant, but it'd be good to have immunologists' thoughts on the model or the mechanism. It sounds like there's still a lot to understand about immune mediated disease and why we struggle to switch off errant processes for good, so surely new thinking is of interest.
 
Jonathan Edwards said:
No idea @Sasha, but I suspect quite a lot of downloads will be PWMECFS.
It would be nice to have a third review, even some criticism of the model, but maybe nobody can find anything to criticise!;)
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I think you said that Qeios has some AI thing that automatically sends papers out to reviewers it thinks would be appropriate. Is it worth doing something a bit more hands-on, not necessarily to elicit reviews but just to dangle this interesting carrot in front of some useful people who might want to get involved?
 
Andy said:
In an ideal world who would you want to take notice of it? Especially who outside the current ME/CFS research field?
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I would like people like interest from peopple like Matt Brown, the senior author of a paper recently posted on T cell clonality research. The vast majority of researchers in the autoimmunity/ autoinflammatory disease field seem to have no real aspiration to understand exactly how each one goes wrong. My hope is that with genetic data we will not only have a key to understanding exactly why things are going wrong in ME/CFS but that will have major knock on effects on understanding of diseases like lupus, ankylosing spondylitis and narcolepsy/cataplexy.

But that conversation, which Jo C and I tried to start with our 1999 Immunology paper on autoimmune disease in general has never got started in 25 years. Why that is continues to puzzle me but maybe the time has come for that to change.

Closer to ME/CFS, I would hope people like Andreas Goeber might take an interest because I think he may be on to something in severe fibromyalgia but may need to consider variations on the standard theme.

And of course I would like people like Danny Altmann to take an interest, since he is already on the DecodeME board and in a position to start thinking about what the results might mean. And people like Andreas Radbruch, who has a detailed understanding of plasma cell dynamics in disease.
 
Sasha said:
I think you said that Qeios has some AI thing that automatically sends papers out to reviewers it thinks would be appropriate. Is it worth doing something a bit more hands-on, not necessarily to elicit reviews but just to dangle this interesting carrot in front of some useful people who might want to get involved?
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It might be, but there is a sense in which this paper was deliberately written to be read alongside the results of DecodeME, even if we did not know what those were going to be at the time. As we say at the beginning, the DecodeME results will provide tests of any model framework such as this.
 
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