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

[Jonathan Edwards]

But what do you mean by «stereotyped history of post-infective illness»?

In Reiter's the post-infective illness is quite different from the initial infection and occurs with a delay of several days. In rheumatic fever the illness is different from the original infection (sore throat) and occurs with a few days delay. The problem with rheumatic fever is that it may not strictly be post-infective because if you remove the organism it disappears, even if there may be effects of scarring years later. So rheumatic fever may be a 'secondary infective illness'.

The point of the paragraph is to indicate that although ME/CFS often appears to follow an infection the evidence for some specific triggering of an adaptive immune response is less clear than in something like Reiter's. We later come back to the idea that T cell populations may be expanded but at this point in the story I am more concerned with dismissing a knee-jerk assumption that this is some sort of antigen-specific 'triggering of autoimmunity' with all the implications about mimicry that people are so obsessed with.

I think Lidbury has either misunderstood what I am saying or has misinterpreted what he thinks he has read about symptoms appearing after 12 weeks

 

[Utsikt]

but at this point in the story I am more concerned with dismissing a knee-jerk assumption that this is some sort of antigen-specific 'triggering of autoimmunity' with all the implications about mimicry that people are so obsessed with.

Thank you! So essentially saying that although it might start with an infection, the specifics of that infection probably doesn’t have much to do with ME/CFS?

 

[Jonathan Edwards]

So essentially saying that although it might start with an infection, the specifics of that infection probably doesn’t have much to do with ME/CFS?

Yes, that is the central point.

 

[Peter T]

I am not quite sure what Lidbury is claiming. He says that 12 weeks are needed to see the appearance of idiopathic, long-term fatigue, PEM, and associated symptoms.

My personal experience was that I could not distinguish between the end of my triggering acute glandular fever (mono) and the start of my ME/CFS. As it was thirty years ago and I did not then have the concept of PEM, I can not be sure, but retrospectively the activity/crash cycle seems pretty much like PEM.

However people report such variation in their onset it makes no sense for any one to assert a definite time period for the emergence of specific symptoms. We just don’t know.

 

[Jonathan Edwards]

Thinking again about the text Lidbury thinks is 'incorrect':

“No consistent macroscopic or microscopic structural changes have been found in the brain,…”.

I think I want to stick with that. 'Consistent' can mean various things but in the context what I think I was meaning is sufficiently consistent across all ME/CFS patients for it to be likely to be part of the explanation for symptoms. In other words, what people call a diagnostic biomarker. I am pretty sure that no studies have found that - just statistical trends.

This is not an unreasonable thing to require. Research often finds statistical differences that may be of huge interest in telling us about things that are importantly, but indirectly, relevant to causal pathways. But if we are looking for something that is 'showing us what is going on behind the symptoms" it needs to be there in all cases and not in normal people - with some limited caveats.

People with ME/CFS do not consistently show any one particular change on brain imaging as far as I know.

 

[Hutan]

We have moved posts discussing the possibility that people with ME/CFS are immunocompromised to a new thread:
Are people with ME/CFS immunocompromised?