Review Advocating the role of trained immunity in the pathogenesis of ME/CFS; a mini review, 2025, Humer et al

That’s a great way of putting it @Kitty and I absolutely agree that things which may on the surface look it, don’t necessarily contradict each other.

 

That’s true @Trish
It was part an idle counterpoint. So maybe not worth thinking too much about.

But I suppose I was also thinking about self selection. We’re the ones that don’t get better. I guess that’s what ME/CFS is but maybe that’s not all it is?

We know people get better earlier, we know some do later, sometimes they’re dismissed as ‘not having real ME/CFS’ (I’ve thought his often). But is that true? We recently saw DecodeME reporting the longer people have had it the worse they are, but is that people actually getting worse disease? I don’t think we know for sure…

What if most people who get what we have do get better, but within that earlier period? Maybe if things had gone differently I would have got better and never considered I had ME/CFS, or maybe I would have bounced along as mild with or without relapses and it would’ve been called something else, or…? I don’t know is the truth.

I’m watching my Mum’s PD at the moment and while she can do more than me at the currently, she won’t be able to for long. ME/CFS is horrific but it has a static or variable nature rather than that sort of clear and inevitable degeneration. Maybe that’s shaping my thoughts too.

 

Maybe a more succinct response would be..

Maybe more people get better or are asymptomatic in some way so we don’t record them as having ME/CFS. But when we know more we’ll find they did have this same thing but something took a different path. Like, loads of people get Flu but only some get very ill or die, do we say only those that end up in hospital had Flu? Maybe this isn’t a great comparison!

Maybe I’m just in a questioning, uncertain and philosophical frame of mind atm. I’m sure another time I would be much clearer and firmer that this is what ME/CFS is and I’ll fight anyone who says otherwise!

 

I suppose the question is, maybe, suppose we had a test? And it would be like having high blood pressure without measuring your blood pressure, and being symptom-free (since I gather that most people with high blood pressure have no symptoms until they have a stroke or something).

 

But ME/CFS as currently defined is the presence of symptoms, so by definition there is no asymptomatic ME/CFS. If you are HIV positive but don't have AIDS then by definition you don't have AIDS.

I suppose this discussion is largely irrelevant because once you understand pathophysiology, ME/CFS as we understand it now doesn't exist in the same way anymore and becomes a newer concept (and quite likely multiple different concepts).

 

I don't think that's correct. I'd say that ME/CFS isn't currently defined as the presence of symptoms but diagnosed by the presence of symptoms. It's diagnosed b symptoms because we don't yet have a test.

 

But from my understanding a syndrome is nothing but the presence of certain symptoms that are deemed to be indicative of an underlying process. Once you know the underlying process you don't have a syndrome anymore. So by definition is can only be defined as the presence of symptoms and that these symptoms are indicative of some mutual underlying processes.

In your scenario the people that test positive on such a test, without having symptoms, still won't have what we consider ME/CFS today and the people that experience symptoms but don't test positive will still have what we consider to be ME/CFS today. So there is no argument there as your test does not replace the concept of "ME/CFS today", it forms part of something that is our understanding of "ME/CFS tomorrow".

Once something that indicates pathophysilogy starts existing those things start becoming irrelevant as it won't be a test for ME/CFS anymore because ME/CFS as we now understand likely stops existing and will merge into newer concepts some of which might not be syndromes anymore.

 

True, you probably have a disease.

But can that disease also be asymptomatic, or minimally symptomatic, or only sporadically so?

 

You can have cancer without it causing any noticeable symptoms.

I had to look it up, and this is how ‘symptom’ is defined in a medical context (according to this source):

Something that a person feels or experiences that may indicate that they have a disease or condition. Symptoms can only be reported by the person experiencing them. They cannot be observed by a health care provider or other person and do not show up on medical tests. Some examples of symptoms are pain, nausea, fatigue, and anxiety.​

 

There are probably lots of diseases, but I think what @Sasha might be trying to chase down is whether it applies to ME/CFS.

Can you have it as a tendency that doesn't always manifest? I imagine so, and that might be how it works in most people—it doesn't show up, until it does. But maybe there are other aspects to it, I'm not sure.

 

But cancer is not a syndrome. If you have inherited cancer syndrome that doesn't mean you have cancer and vice versa.

Asymptomatic ME/CFS makes no sense in our understanding of ME/CFS today. It might make sense in our understanding of ME/CFS tomorrow but in that understanding ME/CFS isn't ME/CFS anymore, so what are we even discussing?

 

Strictly speaking I think we have to take EndME's view as correct here. ME/CFS is a syndrome of symptoms. A syndrome is based on the idea that there is good reason to think there may be some sort of common causal path for those with it but it remains defined as the symptoms until we can identify whether there really isa common path.

Acheson proposed ME as a disease due to some specific unknown virus. That has left people thinking ME/CFS is a disease but it isn't yet, and it may be six.

 

It doesn’t apply to ME/CFS as its currently defined because you can’t have ME/CFS if you don’t have the symptoms.

In theory, there might be some biological feature that is required for ME/CFS to develop, but its presence doesn’t mean that you have to be ill right now. An example would be the hereditary genetic mutation that causes Huntington’s Disease. You have it all your life (and can always detect it in your DNA), but you might not have any symptoms until you’re 50.

 

I can see that perspective but I think that @hotblack's original question of whether you can have asymptomatic ME/CFS makes that perspective problematic. If we assume that the ME/CFS syndrome has a common causal path, and that ME/CFS is the only name that we're calling the illness, then if someone with that illness doesn't have any symptoms and yet the causal path is working away, don't we have to say that someone has asymptomatic ME/CFS?

 

Huntington's has a different dynamic in that there is a single gene cause that leads to a process that manifests late.

I think it has to be reasonable to say that someone who goes through cycles of ME/CFS symptoms but has 'clear patches' when they would not satisfy criteria, as some members have described, can be said to have ME/CFS throughout. There might be a prodromal phase, as has been suggested by some members but at present that isn't really relevant to discussion of real situations.

 

No, not as things are. All we can say is that we suspect that some people may be on causal paths that one day may turn out to be one of those that lead to ME/CFS.

As soon as one starts using the term ME/CFS to mean the cause of the symptoms we call ME/CFS you get into a terminology that makes no causal sense. A causes A. That is not an unusual situation. It is rife throughout medical chat. Osteoarthritis is what causes osteoarthritis, don't you know. Diabetes is the cause of diabetes. Doctors actually think like that without realising. But on S4ME we are made of sterner stuff.

 

In real life I would never tell anyone like that that they didn’t have ME/CFS during the good patches.

But if ME/CFS is strictly defined as a set of criteria and a certain level of impairment, on paper they did not have ME/CFS during the good patches. But they very well might have had whatever causes ME/CFS all along.

 

Yes, it was mostly an example of how it is possible to test positive for something that causes illness without currently being ill in the normal sense of the word.