What evidence is there that ME/CFS is more autoimmune than chronic infection?

[Sidereal]

Has any loss of electrolytes been demonstrated in the PEM period?

I haven't seen anything in the published literature but anecdotally many patients benefit from supplementing them.

 

[MeSci]

Has any loss of electrolytes been demonstrated in the PEM period?

I don't know, but I'm willing to bet that it happens commonly. It needs to be researched, if it has not been.

If you look at this paper on d-lactic acidosis, Figure 6, you will see that organic acids are/can be excreted as their Na and/or K salts. So perhaps the more lactate/lactate acid in the body, the more Na and/or K is lost.

I certainly experience solute diuresis as part of my PEM, as I get polyuria which is not relieved by desmopressin, thus is driven by solutes. Sodium is one of the commonest solutes to be lost in solute diuresis, and I have experienced severe hyponatraemia following over-exertion. I also frequently experience cramp during PEM, which is also commonly due to hyponatraemia.

 

[Simon]

Gut enteroviruses

This research culminated with the work of John Chia in the US in the mid-2000s, which replicated these British findings. These studies, and there are quite a few of them, found enterovirus RNA was as much as 20 times more prevalent in ME/CFS patients compared to healthy controls.

I will say that in the context of persistent presence of infection Dr Chia does seem to have a lot more controlled evidence than most of the other theories. With regard to why his theory is ignored - so far I have made enquiries amongst people who worked in the virology environment that the early UK papers come from and the view seemed to be that finding enteroviruses does not take you very far in the end - you can find them in a lot of normal people.

I've abandoned attempts to catch up with this thread but just wanted to comment on this, in the light of John Chia's recent paper: Functional Dyspepsia and Chronic Gastritis Associated with Enteroviruses. This study again found high rates of enterovirus in mecfs patients, but unfortunately it wasn't specfic to mecfs, so I think if gut enteroviruses are an example of a chronic infection causing mecfs we need to factor in this new findig. I commented on another thread:

Interesting stuff., Chia has demonstrated the presence of enterovirus in stomach biopsies in a new and very large cohort of mecfs patients (n=416, collected 2006-2012) - backing up his earlier findings from the 2007 paper.

Immunoperoxidase staining demonstrated:

• enterovirus VP1 in 343/416 (82%) and 53/66 (83%) of the stomach biopsies from FD patients with and without ME/CFS, respectively,
  
• dsRNA in 268/ 416 (64%) and 41/65 (63%) in the two patient cohorts, respectively (Figure 1). 9/47 (19%) and 5/46 (11%) of the controls stained positive for VP1 and dsRNA, respectively (p < 0.01, χ2 test with Yates correction).

The team also showed that potential cross-reaction of test antibody to a protein other than VP1 couldn't account for these results (this was a crticism raised about the original 2007 study).

However, the study also showed the same high rate of enterovirus in functional dyspepsia whether or not they have mecfs, suggesting that enterovirus infection alone is unlikely to be the cause of mecfs. We also don't know what proportion of mecfs patients have functional dyspepsia (it's 10-20% of the general population, the paper says). Presumably Dr John Chia sees patients with stomach problems.

As @Bob says, maybe the enterovirus is opportunistic. Or maybe it's a trigger. Or something else... But still, interesting stuff.

The point is that all these mecfs patients had functional dyspepsia and there was no differene with the relevant control group ie functional dyspepsia patients without mecfs.

It seems that one reason the original striking finding of high rates of enterovirsues in the guts of mecfs patients edit: WASN'T REPLICATED was that researchers thought that they'd struggle to get ethical permission for stomach biopsies, a fairly invasive procedure. Perhaps all Chia's mecfs patients did have GI problems, which would presumably justify the biopsy on clinical grounds alone (any clinician want to comment on that?):

Most patients with CFS have persistent or intermittent, upper and/or lower gastrointestinal (GI) symptoms, referred to as functional dyspepsia or irritable bowel syndrome.16 17

16 Frissora CL, Koch KL. Symptom overlap and comorbidity of irritable bowel syndrome with other conditions. Curr Gastroenterol Rep 2005;7:264–71.
17 Henningsen P, Zimmermann T, Sattel H. Medically unexplained physical symptoms, anxiety, and depression: ameta-analytic review. Psychosom Med 2003;65:528–33.

I don't know how good the evidence is that most mecfs patients have gut problems, but it certainly seems to be a common symptom.

Anyway, my point is that enteroviruses seem to be linked to GI problems, irrespective of mecfs, which presumably argues against them having a causal role.

 

[cigana]

Schutzer's study addressed the question of whether or not ME/SEID and Chronic Lyme are the same disease:
Distinct Cerebrospinal Fluid Proteomes Differentiate Post-Treatment Lyme Disease from Chronic Fatigue Syndrome
"...Post-treatment Lyme and CFS have distinguishing CSF protein complements..."

The conclusion was that these are 2 different diseases, since they can be differentiated with the protein tests described. I don't think that's a final decision but in terms of what we do know it's the best evidence yet (?)

In my opinion, this study was the most impressive ever undertaken in ME/SEID research, since it clearly distinguishes people with ME/SEID from healthy people.

 

[duncan]

Yep, cigana, I agree, this was pretty cool. Natelson and Coyle...two researcher I have conflicted opinions about in their respective areas of expertise.

Regardless, you'd think the NIH would rush out to replicate, since this is a U.S. effort

Well, as far as I am aware, no such replication efforts are underway. The NIH does have a 20-year ongoing study looking at chronic Lyme, but I am told that it isn't currently looking for protein signatures, and is restricting that study to conventional Lyme metrics like ELISA and WB and C6 tests.

 

[halcyon]

Anyway, my point is that enteroviruses seem to be linked to GI problems, irrespective of mecfs, which presumably argues against them having a causal role.

This is an overly simplistic argument. I don't want to belabor this point because people are probably tired of hearing it, but it's relevant because we're talking about cousin viruses. Everyone got poliovirus infections, only a small percentage developed poliomyelitis. Everyone gets enterovirus infections, only a small percentage develop serious consequences from them, including ME. Enterovirus infections cause different manifestations in different people, depending on the virulence of the strain and host factors in the individual at the time of the infection. In some it will be limited to the GI tract, others it will disseminate to the heart and cause myocarditis, others the liver causing hepatitis, still others the brain and meninges causing encephalomeningitis. Finding chronic enterovirus infections in people with chronic GI conditions doesn't prove that enteroviruses don't cause ME. It all depends on where the virus disseminates to. Enterovirus has been found in the GI tract, muscles, and brains of ME patients.

 

[duncan]

Perhaps a stupid question, but the Schuzter/Natelson/Coyle study had healthy controls vs chronic Lyme vs ME/CFS - do enteroviruses and herpes viruses etc. have protein signatures peculiar to each major disease in CSF exams?

I guess what I am trying to get at is this study split the population into two broad illnesses, while demonstrating overlap. Could it have been further refined to demonstrate distinct protein fingerprints in spinal fluid for each of the different suggested ME/CFS trigger mechanisms?

 

[adreno]

Enterovirus infections cause different manifestations in different people, depending on the virulence of the strain and host factors in the individual at the time of the infection. In some it will be limited to the GI tract, others it will disseminate to the heart and cause myocarditis, others the liver causing hepatitis, still others the brain and meninges causing encephalomeningitis.

But then it would come down to the immunocompetence of the host (as a determining factor).

 

[halcyon]

But then it would come down to the immunocompetence of the host (as a determining factor).

Yes, immunocompetence would be one of the critical host factors. I don't understand the point you're trying to make I guess.

 

[leokitten]

Lets wait until there is an effective treatment for enterovirus and other RNA viruses and then see if people with ME/CFS get better from it. Without any effective treatment we won't really know and to me it's a bit pointless to go on and on debating this.

Drugs like Favipiravir

 

[adreno]

Yes, immunocompetence would be one of the critical host factors. I don't understand the point you're trying to make I guess.

Just semantics, you might say. My point is that the emphasis is on the immune system as a determining (causative) factor for developing ME, rather than the virus itself.

 

[halcyon]

Without any effective treatment we won't really know and to me it's a bit pointless to go on and on debating this.

Without widespread acceptance that enteroviruses can cause severe disease, including ME, development of these treatments is going to be needlessly slow.

 

[halcyon]

Just semantics, you might say. My point is that the emphasis is on the immune system as a determining (causative) factor for developing ME, rather than the virus itself.

Gotcha. "Host factors" is an epidemiologic term that covers things such as age, gender, race, nutritional status, genetics, etc. Things that can have an influence on immune competence. But yes I agree.

 

[leokitten]

Without widespread acceptance that enteroviruses can cause severe disease, including ME, development of these treatments is going to be needlessly slow.

The ebola outbreak in Africa and the West at least helped to push some of this forward.

 

[leokitten]

Other investigational new drugs against RNA viruses: https://en.m.wikipedia.org/wiki/FGI-106
https://en.m.wikipedia.org/wiki/BCX4430

 

[Freddy]

And the only published evidence for non-viraemic latent infection that looks at all convincing to me is from Carmen Scheibenbogen on EBV - and of course rituximab is good treatment for EBV so we cannot have things both ways! I guess the latent virus idea may have come from Lerner but as far as I know for him it was just a speculation. He backs it up with a paper that seems to jump about from one virus to another and does not really add up for me.

@Jonathan Edwards Do you mean the following paper:
"Deficient EBV-Specific B- and T-Cell Response in Patients with Chronic Fatigue Syndrome" in PLOS ONE?

If so, what is convincing to you and can therapeutical consequences arise from that (antiviral therapy <--> non-viraemic laten infection)?

 

[alkt]

Maybe they are more concerned with getting bogged down in endless debate when they need to be working on pathology, treatment and cure?

endless debate may not get us anywhere but it is an interesting and sometimes amusing distraction. i have no doubt my mind will go awol before people run out of interesting theories or thoughtful disagreements. a debate can be educational .without coming to any definitive answers

 

[alex3619]

endless debate may not get us anywhere but it is an interesting and sometimes amusing distraction. i have no doubt my mind will go awol before people run out of interesting theories or thoughtful disagreements. a debate can be educational .without coming to any definitive answers

Debate serves a purpose for patients, and carers, and even the general public. However let me ask the question: would we want a leading researcher who might engage in research to find a cure or test spend their time here instead, fielding questions? Short visits are OK. If they were here a lot then they would be letting us down, unless they are retired or semi-retired. I was referring to our leading researchers, not patients, carers, journalists etc.

PS I think researchers also need to engage in questioning and debate, its my philosophical position, but that is why we have research conferences, research seminars, and so on. In fact I wish researchers on ME and CFS spent more time debating with each other.

 

[BurnA]

Can a link be made between other symptoms such as POTS or rhinitis ( both may have links to immune system ) which could lead to the conclusion that ME / CFS is autoimmune ? Ie one autoimmune problem causing may symptoms ?

 

[Hip]

Can a link be made between other symptoms such as POTS or rhinitis ( both may have links to immune system ) which could lead to the conclusion that ME / CFS is autoimmune ? Ie one autoimmune problem causing may symptoms ?

Certainly if POTS turns out to be autoimmune (and one study which found autoantibodies to the α1, β1 and β2 receptors in POTS suggests it may well be), that would indicate there can at least be very common autoimmune comorbidities of ME/CFS; however, that does not necessarily imply that autoimmunity occurs as part of the pathophysiology of ME/CFS itself.

There are also other common comorbidities of ME/CFS which are autoimmune or suspected autoimmune, such as Hashimoto’s thyroiditis and Sjögren’s syndrome.


It's also of interest to note that many common comorbidities of ME/CFS tend to be found more frequently in patients with known autoimmune diseases, and this fact might perhaps offer some evidence for an autoimmune etiology of ME/CFS.