Notice about a forthcoming paper: A Proposed Mechanism for ME/CFS Invoking Macrophage Fc-gamma-RI and Interferon Gamma

What do you make of the fact that some people — and I’d say it might not even be a small subgroup — can lessen the impact or occurrence of PEM with NSAIDs? And it seems to help specifically with PEM. How, if at all might this fit with your ideas?

I remember a renowned specialist in diabetes and metabolic diseases (not an ME/CFS specialist, to be fair) once told me—long before I took PEM seriously—that ME/CFS patients who overexert should probably take an NSAID to lessen the impact. It wasn’t specifically about pain; I remember him saying, 'What else would it be', meaning PEM?—I think hinting at some kind of prostaglandin-mediated issue.

It seems to work/be true for some at least.

 

I reckon @hotblack's right. The only person with the admin password's on leave, and everybody thought somebody else was going to ask her for it, but nobody did. This is how every office in the world works.

 

NSAID block production of prostanoids, which also sensitise nociceptor nerves. In the model I am thinking of I would expect NSAID to have some helpful effect. In other diseases we often see benefits from blocking several different mediators - presumably because they are all in different ways necessary to the final generation of symptoms. Wherever gamma interferon is operating I would expect prostanoids to be likely to be part of the story.

 

..

A couple more questions while we’re waiting for the paper to drop:

1. If your hypothesis proves to be correct, can you suggest what the disease should be called instead of ME/CFS?

2. Do you think that ME/CFS could be more than 2 diseases?

I know that I am not alone in wondering if I may have a different illness or disease to the majority of people with ME/CFS, because some of my symptoms are atypical. I’m also aware that I have very different symptoms to at least one other person on this forum who is atypical in a different way to me. It is certainly possible that we all have different presentations of the same immune and neural processes but equally I can’t see why there couldn’t be more than 2 different diseases which are currently grouped under the ME/CFS umbrella.

Naturally, I hope that any advancement in the understanding of the mechanism of any subgroup of people ME/CFS will apply to me. But I’m also confident that any advancement would benefit everybody with the diagnosis, even if it only applies to a subgroup – provided the remainder are not thrown under the BPS bus.

 

Very interesting! I’m a long-term very severe patient. NSAIDs change things a bit for a while—not just the pain. I have no elevated inflammatory markers on standard labs; quite the opposite—mine have been described as 'suspiciously low.' Interestingly, there was a Gulf War illness paper showing that the most severely affected patients—those with the worst mitochondrial markers on muscle biopsy—also had the lowest inflammatory markers, if I remember correctly.

 

No idea really but maybe something like Gamma Interferon Mediated Exertion Intolerance.

I think it will turn out to have a degree of modularity, just like other chronic immune diseases. So everyone is in a slightly different place in a huge Venn diagram. A small proportion of cases will probably have causal input from quite distinct factors - either genetic or otherwise. The common factor would be the engagement of FcRI and gamma interferon. There might also be some people with the same clinical picture who do not have these involved - who should then be divided off into a separate diagnostic group - but that would be much more speculative.

 

Might that explain my nagging but unprovable suspicion that I get some benefit from sulfasalazine?

It isn't substantial, but I've been asked to stop and restart the drug a few times and it was enough to notice.

 

@Jonathan Edwards please can I ask what (in brief layman's terms) the distinction is between the two types is?

Would we be able to tell from symptoms which bucket we fall into?

 

GIMEI... That's going to end up sounding like GIMME...

 

GIMEI? Interesting ring, would be a funny sounding acronym.

As ABBA would say:

 

Oh well I see we had the same reflex seconds apart

 

Though I went straight to horror and you went straight to Abba!

 

Gamma Receptor, Interferon Mediated, Nociceptor Exciting, Serious Syndrome

 

This is the sort of thing the crowd usually seems to decide, even when there are efforts to the contrary.

History has a hand in it too, I'd put ten bob on there being an entire Wikipedia page of diseases whose names bear no relation to the cause or even the resulting pathology.

If I had to guess at a new name, it would be that the (apparent) lack of structural damage would be referenced. That might be important as part of diagnostic processes—separating it from other candidates with a similar presentation.

I'd also guess a genetic influence might not be referenced, even if it's there.

I'd prefer something that could also be written as, say [insert initial of favourite psychobehaviouralist] Is A Dolt.

 

Or for more fun maybe we can find something that works for Gimlet or Gimli?

 

As pointed out by my partner.

GIMEI means “fake name” in Japanese, which isn’t a great start lmao

https://www.tanoshiijapanese.com/dictionary/entry_details.cfm?entry_id=21312

 

Would it be better for the name to be an acronym or a initialism? [Edit: see: https://www.s4me.info/threads/patie...e-2025-miller-et-al.44129/page-17#post-611965]

How about LMT disease? (a Little More T cells)

 

It all depends on whether the linked genes all crop up in the same lot of people or whether there are actually two lots of people, one with one lot of genes and the other with the other. I gather that one can look for this in genetics data but it gets tricky if you start looking at all sorts of different combinations because you end up having to multiply your p values roughly by the number of combinations you try. But in broad terms the threshold that gets overridden with abnormal signals may be lowered either by neurological or T cell factors.