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

[Ravn]

This would be quite different from autoimmunity and probably not involve any specific autoantibody, although immunoglobulins might get caught up in signalling.

I’m looking for a simple, bordering simplistic, way of communicating the difference between autoimmunity and the host vs host concept. On the face of it both sound like cases of self attacking self

Have I understood correctly that the key difference between the two is that in autoimmunity autoantibodies are involved and in host vs host they are not and it's more that immune cells attack directly?

This idea came out of a lengthy chat with Jo Cambridge, who has recently been laid flat by treatment with allogeneic lymphocytes and previously suffered with graft versus host problems

Best wishes to Jo Cambridge. Very sorry she is having such a rough time again

 

[Jonathan Edwards]

Have I understood correctly that the key difference between the two is that in autoimmunity autoantibodies are involved and in host vs host they are not and it's more that immune cells attack directly?

That is a fair start.

Being more precise requires a more precise account of how host versus host reactions would work and I have to say that I have not got that clear in my mind. I thought the graft versus host case was a useful place to start and hoped to clarify to what extent a host versus host reaction would involve the same mechanisms and to what extent not.

Edited out a bit on my not understanding GVH, which I realise I do understand, although I realise things are a bit more subtle than often implied.

GVHD involves recognition of the host's HLA (or minor compatibility gene products) as 'foreign'. For host versus host this would not apply. But we know that there are a number of situations where the immune system recognises its own cells as redundant or suspect - for instance when virally infected or making a harmful antibody. The suggestion is that something goes wrong with the rules for those interactions.

 

[Creekside]

Is the idea here that the neural aspect is purely via signalling

Something that came up on PR: can long-lasting neural patterns form in response to immune activation events, resulting in symptoms, which then responds to future immune signals? Something like a "sickness behaviour habit" in response to even a small level of a cytokine or whatever.

It doesn't fit well with some aspects of ME, but an interesting concept.

 

[hotblack]

The suggestion is that something goes wrong with the rules for those interactions.

So, you could say it’s the maintenance mechanisms going wrong rather than the pathogen recognition mechanisms? The cleanup crews rather than the surveillance? (Although there’s obviously lots of crossover, just thinking back to some previous ideas and discussions).

 

[Jesse]

Interesting theory! So basically immune cells are fighting each other in the lymphatic system and this triggers something similar to sickness behaviour (which normally only occurs when immune cells are fighting an infection).

@Jonathan Edwards if I may:
1. That does make me wonder: why do other diseases where the immune system is heavily involved (like autoimmune diseases) not trigger sickness behavour?
2. The link with tender lymph nodes is very obvious, but is there be any possible link with sore throats?

 

[Jonathan Edwards]

@Jonathan Edwards if I may:
1. That does make me wonder: why do other diseases where the immune system is heavily involved (like autoimmune diseases) not trigger sickness behavour?
2. The link with tender lymph nodes is very obvious, but is there be any possible link with sore throats?

Number 1 is a good question. My guess would be that sickness behaviour is rather specifically tied to certain immune signals, maybe those associated with threat of intracellular infection or other evidence of cells being damaged or dangerous and requiring deletion. In fact, 'sickness behaviour' may be too simple a concept here, with different cytokines producing different profiles, some with fever, some with pain etc perhaps.

Autoimmune diseases like RA and lupus do come with some degree of general symptoms - RA has fatigue and muscle pain, lupus has fatigue, pain and also fever, but admittedly these are in the background in comparison to specific local manifestations.

Part of the answer may be that autoimmune disease is largely mediated by antibody and the signalling systems involved recruit B cells and CD4 helper cells but not so much CD8 cytotoxic cells or NK cells (which deal with intracellular threats).

Sore throats can be due to infection of the pharynx epithelial cells with things like cold viruses but I suspect that in many cases they actually reflect activation of cells and swelling of the lymphoid ring (of Waldeyer) that forms the tonsils and adenoids which lie directly underneath the epithelium.

An intriguing side effect of rituximab is that it produces a pricking sensation in the throat, which is almost certainly due to killing of B cells in Waldeyer's ring.

 

[hotblack]

Sore throats can be due to infection of the pharynx epithelial cells with things like cold viruses but I suspect that in many cases they actually reflect activation of cells and swelling of the lymphoid ring (of Waldeyer) that forms the tonsils and adenoids which lie directly underneath the epithelium.

Interesting. It’s always been that back of the mouth/soft palate area that has become tender/sore for me, and over recent years I’ve found it managed quite well with small quantities of Difflam (Benzydamine) spray.

 

[T&O]

Interesting. It’s always been that back of the mouth/soft palate area that has become tender/sore for me, and over recent years I’ve found it managed quite well with small quantities of Difflam (Benzydamine) spray.

Me too Hotblack.
“Difflam Forte”, along with glands that feel tender and huge (neck underarms and groin).
Put some of the usual sore throat down to a drippy nose/post nasal drip.

 

[jnmaciuch]

Interesting. It’s always been that back of the mouth/soft palate area that has become tender/sore for me, and over recent years I’ve found it managed quite well with small quantities of Difflam (Benzydamine) spray.

That's an interesting detail--if I'm not mistaken, benzydamine acts to block prostaglandin production and since it's a spray it would act locally. Can anyone else report similar experiences?

If yes, then between this and the handful of pepole corroborating "crunchy necks" and NSAIDs working to suppress PEM, it could make a good case for local prostaglandin signaling driving some symptoms for a subset of pwME.

Which would be very interesting if we actually could define a coherent disease subtype by a particular mechanism.

 

[hotblack]

That's an interesting detail--if I'm not mistaken, benzydamine acts to block prostaglandin production and since it's a spray it would act locally. Can anyone else report similar experiences?

I’d never looked in detail at the mechanism before, it was just something that was recommended to me by a dentist some time ago who was a fan oral use and I thought I’d give it a go due to the feeling of pain and swelling. It’s reported to have a mix of analgesic and anti-inflammatory effects. I’ve heard mention of some anti microbial properties too.

Wikipedia says

It selectively binds to inflamed tissues (Prostaglandin synthetase inhibitor)

But I can’t find a clear source from its references

While this paper says

benzydamine HCl is a weak inhibitor of cyclooxygenase and lipoxygenase, and needs high concentrations to inhibit effectively prostaglandin and thromboxane biosynthesis. Consequently, the primary mechanisms of benzydamine HCl of action are not related to arachidonic acid metabolism and do not affect the biosynthesis of the inflammation mediators prostanoids, prostacyclin, thromboxane and leukotrienes.

 

[Kitty]

Can anyone else report similar experiences?

Not really—there was a numbing effect, but it only lasted 20 minutes or so. I used to buy it for a painful throat infection, but it didn't do anything for the swollen neck glands and nagging sore throat of PEM. That's a different kind of discomfort.

It's a type of NSAID, which I've never found useful for any sort of ME/CFS pain. Good if I got a sprained joint, though, and it helped a bit with severe menstrual cramps if taken with painkillers with a different mode of action.

The downside was that NSAIDs aggravate asthma quite badly in some people, so I had to limit their use to a day or two. (Can't use them at all now.)

 

[jnmaciuch]

I’d never looked in detail at the mechanism before, it was just something that was recommended to me by a dentist some time ago who was a fan oral use and I thought I’d give it a go due to the feeling of pain and swelling. It’s reported to have a mix of analgesic and anti-inflammatory effects. I’ve heard mention of some anti microbial properties too.

Wikipedia says

But I can’t find a clear source from its references

While this paper says

Interesting, thanks. I’ll need to look into it then. It might be one of the many common drugs where we don’t really know how it works

 

[hotblack]

Interesting, thanks. I’ll need to look into it then. It might be one of the many common drugs where we don’t really know how it works

If you do it would be great to hear what you make of it. I’m not sure what it means by high concentrations. Would topical applications mean local concentration was high enough? Or are the doses used in sprays too low so the other mechanisms are what counts? I couldn’t really make sense of it.

 

[jnmaciuch]

If you do it would be great to hear what you make of it. I’m not sure what it means by high concentrations. Would topical applications mean local concentration was high enough? Or are the doses used in sprays too low so the other mechanisms are what counts? I couldn’t really make sense of it.

From a quick check, the cited reference doesn’t even measure prostaglandins. It looks like they may have mixed it up with MCP1/CCL2, which was suppressed only at the highest concentration tested.

Overall it seems like this drug affects so many mechanisms that it’s probably not helpful for pinning down what exactly is causing the symptom or why the drug helps, unfortunately.