Is ME/CFS a form of Host versus Host disease?

I wonder if issue is focused in lymphatic system would that also implicate glymphatic system in the brain? Not familiar with the overlap or otherwise of those two. But if related could be an explanation for sleep issues as well as sensory & other brain symptoms?
 
Could this theory also explain intermittent GI symptoms in PwME? I endured 3 years of “rumbling appendicitis” as a child but that diagnosis was only given retrospectively. I was in hospital for further investigations of my symptoms which were increasing in frequency & intensity & was very poorly when I had emergency surgery for peritonitis from burst appendix.
I am not aware of any association of ME with appendicitis - but is it possible that in some people have a low level of rumbling appendicitis that does not progress to “bursting”?
 
Not that this is really helpful, but I am always very aware of my lymph glands when they’re tender. The throat ones are generally tender but the groin and armpit ones have made themselves known through the years. In fact, I-didn’t know you had them there, until they started bothering me.
 
Could this also explain painful nodes without swelling? I’ve never had a swollen lymph node in my life but the little devils sure know how to ache. My doctors have been supremely uninterested in anything not swollen so it must be a bit unusual?

How does this line of thought align with the Decode findings? I’ve only skimmed the Decode threads but most of the discussion there seems to be about the brain. Yet when I looked up a few random candidate genes on genecards to my inexpert eye all of them appeared to be expressed in multiple tissues, not just in the brain, and often similarly strongly, including in the immune system

AI tells me that the impact of one and the same snp can vary widely between tissues, depending on the particular role a particular gene product plays in a particular tissue and how critical it is there, it may cause big trouble in one place and none at all in another. So often there are probably good reasons to look at a gene’s role in the brain rather than in other tissues – but still worth having another look at some of the candidate genes through the lens of immunity?
 
StellariaGraminea said:
I wonder if issue is focused in lymphatic system would that also implicate glymphatic system in the brain? Not familiar with the overlap or otherwise of those two. But if related could be an explanation for sleep issues as well as sensory & other brain symptoms?
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The terminology is confusing. The glymphatic system is a system of channels that can carry immune cells, just as the lymphatic system does in the rest of the body. But when I am talking about the lymphatic system here I am really referring to the immune cells themselves and the solid organs within these channels where immune cells collect to talk to each other. For the glymphatics the areas where immune cells collect are to some extent the same lymph nodes (in the neck) that are used by lymphatics. But there also appear to be places like the subfornical organ actually within the brain where immune cells can collect. So yes, direct interaction with brain could fit within this idea.
 
Deanne NZ said:
Could this theory also explain intermittent GI symptoms in PwME?
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I think so, because about 75% of our immune cells are in gut wall. Gut tissue has its own specific trafficking systems so that its own T cell populations can recirculate through gut. They can utilise the MADCAM ligand rather than the VCAM ligand used elsewhere.

But things are complicated. There appears to be a separate mucosal trafficking domain with a different ligand again, relevant to Reiter's conjunctivitis, urethritis and mouth ulcers, but gut is of course a mucosal tissue too. So called Mucosal Associated Innate T cells (MAIT) live in gut but can also access other tissues, and not just mucosal.

Gut is thought of as having a different strategy for its immune defence from the rest of the body because for most of the foreign stuff it meets (food and microbiome) it doesn't want to produce an inflammatory reaction but just keep things in the right place with no fuss. We don't need to be vaccinated against food and microbiome. Coeliac disease seems to be a situation where the gut strategy and the general body strategy get their wires crossed and a T cell response to wheat protein epitopes fuels an antibody response to a self enzyme (transglutaminase).

One variation on this host versus host idea might be that in ME/CFS there is some similar crossing of wires so that cells trafficking through different organs end up arguing with each other when they meet in certain places.
 
Ravn said:
Could this also explain painful nodes without swelling?
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Yes, the idea does not require swelling, just cell activity.
Ravn said:
How does this line of thought align with the Decode findings?
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DecodeME picked out one gene that is particularly involved with gamma delta T cell function, although it almost certainly does other things in other places. It also picked out a hit in the MHC that seemed to be DQ but was hard to interpret. MHC interactions are central to the sort of interactions I am suggesting. DecodeME did not pick out a very strong MHC Class I or II link of the sort seen with many autoimmune and autoinflammatory diseases but together with findings from other groups there is a definite suggestion that ME/CFS is influenced by MHC genes, maybe including NK killing inhibitor receptor genes.

I think we are all wary of the idea that genes are specific to brain, for reasons of possible bias. However, if the genes are producing risk through brain processes that to me is entirely consistent with a host versus host model in that brain related genes could act as volume control switches on the ultimate targeting of brain tissue to generate the symptoms. We know that ME/CFS disables people primarily by making them feel ill and more so with exertion. Feeling ill occurs in the brain. Whether or not the brain contributes actively to signalling loops to further exacerbate immune cell misbehaviour is a moot point but either way is OK.
 
I was wondering whether this lymph idea relates to why I feel like death when I wake up in the morning, to the extent that it's extremely difficult to make myself get out of bed, but when I finally drag myself out and start moving (thus presumably starting up the muscle action that moves lymph), the yuck feeling in my muscles decreases over the course of a few minutes (though doesn't entirely go away).

But if you're talking about immune cells talking to each other in solid lymph tissue, maybe this isn't relevant. Plus, my knowledge of how lymph works and moves is based primarily on folklore and vague rememberings.
 
Sasha said:
But if you're talking about immune cells talking to each other in solid lymph tissue, maybe this isn't relevant.
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It probably isn't much. However, stiffness on waking is a standard symptom of accumulation of immune signals like prostaglandins in connective tissue fluid ~= lymph. But it applies wherever the signals are originating - muscle, joint, skin etc.
 
Is the idea here that the neural aspect is purely via signalling or could there be a marker or cell surface protein which is also present on (some) cells in the nervous system which could also be being directly impacted in this process?

I like the crossed wires idea. Whenever systems interact seems like a prime spot for confusion.
 
Jonathan Edwards said:
It probably isn't much. However, stiffness on waking is a standard symptom of accumulation of immune signals like prostaglandins in connective tissue fluid ~= lymph. But it applies wherever the signals are originating - muscle, joint, skin etc.
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Interesting about stiffness but this isn't stiffness - it's a sick sort of achiness. I used to get something similar if I laid in bed for hours as a teenager at the weekends, but this is it raised to the nth degree, with added yuck.
 
I've had several enlarged lymph nodes at least 5 years before the illness onset. Is it possible for the immune problems to begin years earlier, but symptoms to only appear later, when an additional vulnerability is present that is required to develop the illness?

At least that seems like it might explain the two ages of onset, where the vulnerability factors are related to development around the age of 15, and to something occurring in women around 35 years.
 
hotblack said:
Is the idea here that the neural aspect is purely via signalling or could there be a marker or cell surface protein which is also present on (some) cells in the nervous system which could also be being directly impacted in this process?
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The latter is probably outside this basic idea. It does not require that any neural gene product is going to be an immune target, as it appears to be in narcolepsy.
 
Ravn said:
Could this also explain painful nodes without swelling? I’ve never had a swollen lymph node in my life but the little devils sure know how to ache. My doctors have been supremely uninterested in anything not swollen so it must be a bit unusual?
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In have this too and in my case it's always the same one left in my neck. It's also been looked at and an echo has been made.
It hurts in certain periods but nothing was seen or found.
 
Jonathan Edwards said:
The attack may be specific to immune cells if it involves signals that are normally used for weeding out unwanted immune cells.
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From the Mark Davis talks a few years ago he was thinking ME/CFS could be something like this and was interested in differences in KIR+ cells. Apparently it is normal for these types of immune cells to be very active during infection and they should turn off after the acute infection is resolved but sometimes don't.

However he said the chronic activation mechanism for these cells can be cyclic and so you probably need longitudinal sampling. I remember it took a lot of tubes of blood to get sufficient numbers of the subtype of cells they were interested in. I don't know what the exact subtype of T cell was. Unfortunately the ME/CFS researcher embedded in the Davis lab moved on to another job and that line of exploration stopped.
 
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