Preprint Abnormal T-Cell Activation And Cytotoxic T-Cell Frequency Discriminates Symptom Severity In Myalgic Encephalomyelitis/Chronic Fatigue Syndrome,'25,Lee

There seems no doubt that ME/CFS of the same sort can be mild/mod or severe. However, I think it is quite plausible that people with a diagnosis of ME/CFS fall into two main groups. One of those (A) may also include quite a range of at least partly unrelated problems. I think it likely that the other one (B) has a single central causal path.

I think it is quite possible that A is more or less always mild/moderate but B goes through to severe.
The result then is that studying severe cases gives meaningful answers but if you study A+B you may get a lemon. I also think that it is quite possible that things that are up or down in B are down or up in A. If we are talking about receptor interactions it is quite common to have two similar looking illnesses with some abnormalities opposite.
 
I would not refer to it as different diseases, but if something is progressing there may be different components of the contributing processes becoming more or less deranged or consequential as things get worse.

See this is totally reasonable and I can absolutely see that being the case. But I got the impression that wasn't what Cliff et al were implying.
 
There seems no doubt that ME/CFS of the same sort can be mild/mod or severe. However, I think it is quite plausible that people with a diagnosis of ME/CFS fall into two main groups. One of those (A) may also include quite a range of at least partly unrelated problems. I think it likely that the other one (B) has a single central causal path.

I think it is quite possible that A is more or less always mild/moderate but B goes through to severe.
The result then is that studying severe cases gives meaningful answers but if you study A+B you may get a lemon. I also think that it is quite possible that things that are up or down in B are down or up in A. If we are talking about receptor interactions it is quite common to have two similar looking illnesses with some abnormalities opposite.

What do you make of the fact they found raised IFNy and CD38 in severe patients? As well as TNF and IL-17 which have come up on here before.
 
I could imagine a picture where a group of people have a severe type of ME/CFS, and although they don't have severe symptoms all the time, they are very likely to get them at some point in their illness.

Another groups is very unlikely to get them, though they may have significant impairment. I'd fit that one; I reach my 50th ME/CFS anniversary next year and I've never been severe. I've been very ill a few times with crashes, but the bedbound period was relatively short-lived (weeks, not months) and looked more like an acute illness than severe ME/CFS.
 
I could imagine a picture where a group of people have a severe type of ME/CFS, and although they don't have severe symptoms all the time, they are very likely to get them at some point in their illness.

Another groups is very unlikely to get them, though they may have significant impairment. I'd fit that one; I reach my 50th ME/CFS anniversary next year and I've never been severe. I've been very ill a few times with crashes, but the bedbound period was relatively short-lived (weeks, not months) and looked more like an acute illness than severe ME/CFS.

I think the complication is that I don't know how likely those of us who deteriorated severely from intense exercise would have been to become severe without it. I had a lot of viral hits, several head injuries and countless big exertions in the three and a half years before I began pushing myself, and always found my way back to a mild state.
 
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I think it is quite possible that A is more or less always mild/moderate but B goes through to severe.
The result then is that studying severe cases gives meaningful answers but if you study A+B you may get a lemon. I also think that it is quite possible that things that are up or down in B are down or up in A. If we are talking about receptor interactions it is quite common to have two similar looking illnesses with some abnormalities opposite.
Agree. Back in 2016 when the plan for the NIH study was presented in a webinar, my father (a medical researcher) wrote to Nath to urge them to study patients with severe ME/CFS for exactly this reason. His work was in neural tube defects, and if I remember correctly, his group was not getting results when people with, for example, mild spina bifida were included in their sample alongside more severe cases (A+B). They had their breakthroughs when they separated A from B and looked at B.
 
There seems no doubt that ME/CFS of the same sort can be mild/mod or severe. However, I think it is quite plausible that people with a diagnosis of ME/CFS fall into two main groups. One of those (A) may also include quite a range of at least partly unrelated problems. I think it likely that the other one (B) has a single central causal path.

I think it is quite possible that A is more or less always mild/moderate but B goes through to severe.
The result then is that studying severe cases gives meaningful answers but if you study A+B you may get a lemon. I also think that it is quite possible that things that are up or down in B are down or up in A. If we are talking about receptor interactions it is quite common to have two similar looking illnesses with some abnormalities opposite.

Another thought - you have said that the studies you have had advance sight of will bring significant progress but there will likely be more experiments to do before we are in the home stretch. So does it follow that those studies should probably look at severe patients to get the best results? If so it's important those planning the next batch of studies understand this.
 
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