Revisited - Does ME/CFS more closely resemble an autoimmune disease or a chronic infection?

[TreePerson]

Is it that old people don't get the disease, or is it that it is considered as normal aging consequences for old people to suffer from pain and fatigue and cognitive dysfunctions...

I guess the second point is more likely to be right....

My feeling is that old people don't get it. I mean it's not just pain and fatigue. The PEM is quite distinctive. My mother is 83 she is doing less she has pain in some joints and she gets tired but it's not remotely like what I've got.

Ageing is usually a gradual process of small accommodations and changes. Whereas this tends to come on rapidly over weeks or months and feels very different to normal wear and tear. A massive loss of capacity.

I get that doctors might not recognise it (or should I say be even less likely to recognise it) in an older person but I still think that one way or another it would come to light – anecdotally maybe.

Although I suppose it's just possible that they do get it but that their cancer or Parkinson's disease or other more serious problem masks it.

 

[Hip]

There is a similar thread to this here:

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

 

[Jesse2233]

@A.B.

68 seconds is pretty negligible, especially for the ~$50k a year that Ampligen now costs (tho maybe that extra minute might let you catch an elevator or escape from an alligator).

But from reading anecdotal reports Ampligen's major effects seemed to be not on stamina but on cognitive function. That's certainly the impression Mary Schweitzer and Kelvin Lord's accounts give.

And I keep thinking back to Dr Peterson's claim that Ampligen is effective in 70% of patients if he can select the subgroup (based on HHV virus in CSF and RNAse levels)

Of course these are not studies, so the evidence is anecdotal. It's too bad Hemispherx didn't conduct better trials

 

[Mithriel]

Elderly people have encountered many infections in their lifetime and have antibodies to them. In flu epidemics it is young healthy people who die, not old healthy people as they have some immunity to the bugs.

ME was recognised in epidemics which were often associated with polio epidemics going back to the 30s. Having had an epidemic of ME seemed to give some protection in polio epidemics.

All the enteroviruses are very closely related, in fact laboratory testing for them just looks at enterovirus species and only differentiates them later. It s an accident of histiry that they have different names whereas all the E.coli species which are not so closely related have the same name but different numbers.

Like many epidemics, it became apparent that it could also happen sporadically. Polio, the disease, is an abnormal reaction to a virus which causes a respiratory infection. This seems to happen more often when a person is older when it is encountered, as happens with many childhood illnesses. It was a scary disease as hit people in better areas rather than the slums where most diseases were found. There was polio A and B and abortive poliomyelitis but the research finished when the vaccine went into general use as it was so effective.

Basically, there were no experts left. Some, such as the Behans and Eleanor Bell carried on looking at ME but the expertise was lost. Virology in general was neglected by the eighties, though HIV and PCR brought it back. Medical students still do not get the training in virology, or indeed microbiology, they got in the 70s.

We now know that enteroviruses are sneaky little beggars that can cause chronic infections because of 2 tricks. They do not burst the cell open when they replicate so they stay out of the way of the immune system and they do not copy true so the immune system does not recognise them in the blood.

When CFS was invented the previous research in the UK was ignored. PEM was not considered for decades, though that has been rectified but the emphasis on enteroviral infection was just dropped and has not recovered whether because it is not "sexy" enough or because the expertise had been lost in the US.

Whether it is only a few of us affected or a major cause it is sad and frustrating that we are hardly any further forward than we were in 1980, not because research has shown it is a dead end but because of neglect.

 

[Jesse2233]

Good points @Mithriel, lets hope Dr Davis can answer it one way or another when he runs the viral RNA test on his severely ill samples (same for Lipkins samples)

 

[Jesse2233]

@Hip how do we know the prevalence (or lack therrof) of enteroviruses in healthy control brains? Has this been studied?

 

[Hip]

@Hip how do we know the prevalence (or lack therrof) of enteroviruses in healthy control brains? Has this been studied?

One of the three brain autopsy studies on ME/CFS patients also examined the brains of 8 controls that died of unrelated conditions, and found them to be enterovirus negative, whereas the one deceased ME/CFS patient that they examined had enterovirus in the brain.

The two other ME/CFS brain autopsy studies did not have access to controls, but they again found enterovirus in the brain of the ME/CFS patient.

 

[Mithriel]

There was the VP1 test which quietly died that actually detected viral particles. Many people were positive for that. I became ill in July during a heatwave after swimming in the sea. "Summer flu" is usually a Coxsackie infection. After I had been ill for many years I read Dr Bell's paper and realised that I had ME (later confirmed by a consultant who had been at the Royal Free)

I was tested for Coxsackie B at a random time and had antibodies that showed a high level of current infection. I was given antivirals but I had a new born baby so I didn't feel any better, still tired all the time! That consultant left but I wish I could try them now

 

[A.B.]

There was the VP1 test which quietly died that actually detected viral particles.

It was unreliable. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1293640/

 

[bertiedog]

But not everyone has chronic enterovirus infections in the brain tissues, as autopsies find ME/CFS patients have, with the healthy controls being free of this virus in the brain. And not everyone has chronic enterovirus infections of the muscle tissues, as numerous British studies dating back the 1970s find ME/CFS patients have, but with much less prevalence of such muscle infections in healthy controls.
Of course, if the infections in ME/CFS are triggering or exacerbating autoimmunity or some other immune dysfunction that causes ME/CFS, and since we don't have at present any good antivirals that can fight off these infections, it makes sense to try to treat the immune dysfunction directly, by means of rituximab for example, if that results in improvements in the illness.

What about the idea of modifying the gut so that the pathogenic bacteria are killed and more beneficial bacteria take their place with the idea that in time there will be improvements in symptoms. There seems to be more and more evidence coming out now about the micro biome affecting brain function. Recently there was a study put up on PR about MS and the gut micro biome. Surely it could be similar in our illness?

When stool samples are analysed from healthies and people with ME/CFS there is a big difference. Usually very low levels of the essential beneficial bacteria like bifidobacteria and lactobacillus as well as the beneficial Coli (not the pathogenic one). We seem to have too many of the bad guys and our guts just don't look like the healthy controls. I realise that its early days regarding the micro biome but there does seem to be pretty consistent data showing a big problem in the guts of people with our illness.

I know that Ken Lassenen, CFS Remission feels he has proved this by looking at hundreds of gut results from Ubiome or American Gut Project and referring to published papers but I wonder if this approach will only work for subsets but how large that subset is who knows and surely its got to be worth trying. I have been attempting this over the last month and definitely have had some reactions, some good some bad but I am definitely going to continue. I recently had an American Gut result which was consistent with the above.

Pam

 

[rodgergrummidge]

Thanks I've read many of those threads. I thought it would be useful to revisit this topic given recent developments (cytokine paper, metabolomics, t-cell expansion, cyclophosphamide / rapamycin response, Jarred Younger good day / bad day findings, Lipkin microbiome, lack of CDC enterovirus replication), and with an organized list of factors for either case at the top

Yes @Jesse2233 this is an issue that I think needs to be revisited and reviewed in terms of i) cause or ii) consequence. Thanks for raising. I must admit it is something I have been meaning to read up on........ if I can find a 'gap in the fog', I'll do some reading.........

 

[Hip]

It was unreliable. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1293640/

I have not heard of the VP1 antigen test mentioned in that study (it sounds like they detect antibodies to the enterovirus VP1 capsid protein).

However, note that this is not the same as the VP1 staining of biopsied tissues, which is the method Dr Chia uses to detect enterovirus infections in stomach tissue biopsies.

In the early British research, they typically used PCR testing on muscle biopsies taken from ME/CFS patients, or enterovirus antibody testing using neutralization-type tests (which is the only type of blood test sensitive enough to reliably detect chronic active enterovirus infections).

 

[A.B.]

I have not heard of the VP1 antigen test mentioned in that study (it sounds like they detect antibodies to the enterovirus VP1 capsid protein).

However, note that this is not the same as the VP1 staining of biopsied tissues, which is the method Dr Chia uses to detect enterovirus infections in stomach tissue biopsies.

In the early British research, they typically used PCR testing on muscle biopsies taken from ME/CFS patients, or enterovirus antibody testing using neutralization-type tests (which is the only type of blood test sensitive enough to reliably detect chronic active enterovirus infections).

Do you know if Lipkin has commented on this?

 

[pattismith]

My feeling is that old people don't get it. I mean it's not just pain and fatigue. The PEM is quite distinctive. My mother is 83 she is doing less she has pain in some joints and she gets tired but it's not remotely like what I've got.

Ageing is usually a gradual process of small accommodations and changes. Whereas this tends to come on rapidly over weeks or months and feels very different to normal wear and tear. A massive loss of capacity.

I get that doctors might not recognise it (or should I say be even less likely to recognise it) in an older person but I still think that one way or another it would come to light – anecdotally maybe.

Although I suppose it's just possible that they do get it but that their cancer or Parkinson's disease or other more serious problem masks it.

1-old people with CFS/ME won't push the way younger people with sudden onset of the disease, so PEM won't be as easy to identify.
2-you are talking about acute CFS/ME while many cases are mild cases...

As you said, comorbidities will complexify the problem, CFS/ME is already a very difficult diagnostic to do, but the more the patient gets old, the more difficult it may be...

 

[Hip]

Do you know if Lipkin has commented on this?

I wrote to Prof Lipkin once, asking how well his high-throughput sequencing ME/CFS study would pick up chronic enterovirus infections, and he told me that he would not be able to detect enterovirus in the ME/CFS blood samples that he used (and as we know, chronic enterovirus is usually not found in the blood), and could only detect this virus if you used tissues from an infected organ as the source material for the high-throughput sequencing (which he did not do in his ME/CFS study).

But then he added that "I'm not yet persuaded that anyone has found compelling evidence implicating any agent in CFS/ME." But his email was terse, and he did not provide any explanation for why he thought the existing evidence was not compelling enough.

 

[Hip]

What about the idea of modifying the gut so that the pathogenic bacteria are killed and more beneficial bacteria take their place with the idea that in time there will be improvements in symptoms.

That may help, agreed.

 

[ladycatlover]

Enzyme blocages by toxic triggers like lead or organophosphates?

I'm quite interested in this idea. For 4 years in the run up to me getting ME I was working (part time 5 mornings a week) in a lab where we used a fixative consisting of 3 parts methanol to 1 part glacial acetic acid. Making slides from the fixed cells involved dropping a single drop of the fixed cells from a height of about 2-3 feet onto a slide (that took some practise when I started!) and then waving the slide around in the air like fury to dry the fix off as fast as possible. This was done in the open lab, not in a fume cupboard. The smell of acetic acid was incredibly strong - my clothes would stink of it when I got home. But I'm more worried by the methanol that I must have inhaled along with it.

I also had Hep B immunization when I began work there, set of 3 jabs. Over the 4 years I worked in that lab I gradually had more and more problems with illness, over those years the amount of time I took off sick increased from once in my first year to around 4/5 times in the last year, culminating in going down with ME.

Perhaps for me it was a combination of insults? Followed by a virus that finished me off. I was acute onset, though initially relatively mildly affected but have gone downhill ever since - 25 years now, as shown in my avatar.

 

[pattismith]

I'm quite interested in this idea. For 4 years in the run up to me getting ME I was working (part time 5 mornings a week) in a lab where we used a fixative consisting of 3 parts methanol to 1 part glacial acetic acid. Making slides from the fixed cells involved dropping a single drop of the fixed cells from a height of about 2-3 feet onto a slide (that took some practise when I started!) and then waving the slide around in the air like fury to dry the fix off as fast as possible. This was done in the open lab, not in a fume cupboard. The smell of acetic acid was incredibly strong - my clothes would stink of it when I got home. But I'm more worried by the methanol that I must have inhaled along with it.

I also had Hep B immunization when I began work there, set of 3 jabs. Over the 4 years I worked in that lab I gradually had more and more problems with illness, over those years the amount of time I took off sick increased from once in my first year to around 4/5 times in the last year, culminating in going down with ME.

Perhaps for me it was a combination of insults? Followed by a virus that finished me off. I was acute onset, though initially relatively mildly affected but have gone downhill ever since - 25 years now, as shown in my avatar.

I am very interesting in what you say because I was myself heavily and chronically exposed to formaldehyde for several years before my major crash (the product I used was forbidden not long after I stopped using it, because it is was a known carcinogen....Both Methanol and Formaldehyde are metabolised into Formate (formic acid), which is toxic to mitochondria (I think this would deserves it's own thread...)


Methanol and formic acid toxicity: biochemical mechanisms.
Liesivuori J1, Savolainen H.
Author information
Abstract
Metabolism of methanol, methyl ethers, esters and amides give rise to formic acid. This acid is an inhibitor of the mitochondrial cytochrome oxidase causing histotoxic hypoxia. Formic acid is a weaker inhibitor than cyanide and hydrosulphide anions. The body burden of formate in methanol poisoning is high enough to cause acidosis, and other clinical symptoms. Part of the protons can be attributed to formic acid whereas the most significant acid load results from the hypoxic metabolism. The acidosis causes e.g. dilatation of cerebral vessels, facilitation of the entry of calcium ions into cells, loss of lysosomal latency and deranged production of ATP. The latter effect seems to impede parathormone-dependent calcium reabsorption in the kidney tubules. Besides, urinary acidification is affected by formic acid. Its excretion causes continuous recycling of the acid by the tubular cell Cl-/formate exchanger. This sequence of events may partially explain an accumulation of formate in urine. Occupational exposure to vapours of methanol and formic acid can be quantitatively monitored by urinary formic acid determinations. Formic acid toxicity may prove a suitable model for agents causing histotoxic hypoxia.

https://www.ncbi.nlm.nih.gov/pubmed/1665561

 

[TreePerson]

@pattismith My ME was relatively mild to start with but I still knew there was something really big wrong. Granted had I been 90 I might have put it down to ageing. It will be interesting once there is a test to know whether elderly people do get it. It's still my feeling that by and large they don't.

 

[justy]

Interesting discussion that my brain wont allow me to add too much to.

It would be interesting to see how common comorbidities fit in with either theory - MCAS, POTS, EDS III, MVP etc (I have all of these and you tend to see them more in long term patients)

On the autoimmune side many of us also have high Antinuclear antibodies (or a subset at least, again in long termers more often) In my case Lupus testing and Sjorgrens were negative and NHS wont test for any other antibodies for me.

My feeling is its autoimmune with the antibodies affecting the immune system so we get lots of chronic infections popping up which perpetuate the illness and makes us sicker. that's why I think IVIG nad SCIG helps us so much, but doesn't cure.