CFI Spinal Fluid study from Lipkin and Hornig is out.

[halcyon]

For EBV there is a particular early antigen (EA) IgG antibody that can be tested and if this is positive this is indicative of active infection.

The CDC disputes this.

Anti-EA IgG appears in the acute phase of illness and generally falls to undetectable levels after 3 to 6 months. In many people, detection of antibody to EA is a sign of active infection. However, 20% of healthy people may have antibodies against EA for years.

Source

 

[leokitten]

That's because there aren't any drugs available that can completely eradicate the pathogens in question. You can knock down viral load, and symptoms improve, but once treatment is stopped the viral load increases and symptoms return.

I think the question you should be asking is what has gone so wrong with our immune systems that even after long courses of treatment it cannot control these ubiquitous pathogens like the immune systems of healthy people. Most adults have EBV, CMV, HHV-6, etc but their immune systems keep everything in check.

 

[Kati]

Except that Dr Hornig found the opposite after 3 years in the blood study, and the symptoms continue. I think maybe the key conclusion from that study is that relating symptoms to 'immune activation' does not work. Something more complicated is going on. And to be honest the CSF findings do not look obviously like 'immune activation' to me. A lot of cytokines are lower than the controls. I do not see any support for a continuing infection hypothesis in these studies.

However, the cytokines of the MS groups were also for the most part lower than control, and we all know that MS patients are sick, moreover have demyelinisation disease.

This must be telling for at least something, and this alone needs to get more scientists, especially those working in the MS field at least slightly curious.

 

[halcyon]

I think the question you should be asking is what has gone so wrong with our immune systems that even after long courses of treatment it cannot control these ubiquitous pathogens like the immune systems of healthy people. Most adults have EBV, CMV, HHV-6, etc but their immune systems keep everything in check.

Not everyone with ME has a problem with herpes viruses. In the people that do, it could just be a secondary consequence of the actual problem. It's been found in enterovirus infections that the resulting transient lymphocytopenia can cause VZV reactivations. Also, binding the BCR in EBV infected B cells will trigger reactivation, so an immune response to another pathogen could potentially result in EBV reactivation.

 

[leokitten]

The CDC disputes this.

I'm sure you've seen the EBV antibody panel interpretation tables, combining the EA IgG with the other antibody results help in determining if infection is active. As you wrote the EA for most people is enough.

I will give you my case, soon after falling ill my EBV VCA IgG 1:5120, EA IgG >= 1:640, EBNA IgG >= 1:640 and it continued to be super high each time measured in those first months. I also had CMV IgG 11.5 and HHV-6 IgG 1:1280.

After treatment with Valcyte 900mg qAM 450mg qPM + Famvir 1000mg tid + Immunovir 500mg bid after 6 months EBV EA IgG 1:320, no change in others, CMV IgG 4.98, HHV-6 IgG 1:640. After just over a year I took a break from Valcyte but continued with other antivirals, didn't measure antibodies at this timepoint (I should've). After 1 year 3 months I measured everything again, EBV EA IgG < 0.9 (negative), no change in others, CMV > 10.00, HHV-6 IgG 13.4 (had to change to ELISA).

So the high dose long term antivirals definitely caused the EBV EA IgG to go negative, I wonder then if EA didn't show active infection then why did it follow a negative course just as expected after being so highly positive multiple times before and during treatment?

 

[halcyon]

I wonder then if EA didn't show active infection then why did it follow a negative course just as expected after being so highly positive multiple times before and during treatment?

It can show that, just not in everybody per the CDC.

 

[leokitten]

Not everyone with ME has a problem with herpes viruses. In the people that do, it could just be a secondary consequence of the actual problem. It's been found in enterovirus infections that the resulting transient lymphocytopenia can cause VZV reactivations. Also, binding the BCR in EBV infected B cells will trigger reactivation, so an immune response to another pathogen could potentially result in EBV reactivation.

Totally agree, I do also believe that it's just a secondary consequence and not the root cause.

 

[Snow Leopard]

Why does it have to be just one single pathogen responsible? I agree it would be lovely if this disease matched Koch's postulates, but we've discovered that they were a bit simplistic. Nature is not such a simple place.

I don't see why it's a stretch. The thing we keep finding in common is immune activation. The symptoms we all have in common are symptoms of immune activation. This means that potentially anything that can cause a persistent immune activation could be a suspect.

Each virus tends to have its own signature, I would daresay subgrouping would be more obvious if it was due to more than one pathogen.

In terms of viral possibilities, there was the theory that there were two main cohorts basically the herpes virus cohort (HHV6/CMV/EBV/HSV1/2), and the enterovirus cohort.

But would such cohorts necessarily demonstrate the same set of symptoms?

It still begs the question, why are some people who are exposed to these viruses develop ME symptoms, whereas others don't?

Prospective post-infection fatigue syndrome studies (CFS and CF studies) don't really support the ongoing infection theory either, in terms of pathogen load or type of immune response over time.

The other possibility is some sort of dysregulatory loop between certain bacteria in the gut and the immune system, but I have no idea how this would work.

 

[leokitten]

It can show that, just not in everybody per the CDC.

I honestly think the CDC hasn't tested giving long term antivirals to these people to see what would happen to EA IgG levels, all they've seen is that in some seemingly healthy people they see positive EA IgG. I don't think they've proven that in these people EBV isn't actually doing something subclinical.

 

[halcyon]

It still begs the question, why are some people who are exposed to these viruses develop ME symptoms, whereas others don't?

Why did some people who were exposed to poliovirus get poliomyelitis while others didn't?

 

[SOC]

The CDC disputes this.

Anti-EA IgG appears in the acute phase of illness and generally falls to undetectable levels after 3 to 6 months. In many people, detection of antibody to EA is a sign of active infection. However, 20% of healthy people may have antibodies against EA for years.

Source

Yes, and some percentage of healthy people have sniffles and runny noses for non-infectious reasons. Does that mean that sniffles and runny noses mean absolutely nothing in terms of possible infection? Just because some healthy people have sniffles and runny noses, does that automatically mean everyone with sniffles and runny noses are healthy?

Some apparently healthy people have the symptom, therefore the symptom means nothing in the context of obvious ill health? I don't think so. It's that kind of poor logical thinking in medicine that drives me nuts.

There are many logical questions here. By what standard were the healthy people defined to be healthy? Do we know they didn't have subclinical infections or that they didn't start showing symptoms within days of the test? What testing was done to confirm the people were completely healthy? What percentage of non-healthy people have detectable levels of antibodies against EA? Is it still 20%? Is it more? Is it less? How long do these healthy people retain EA antibodies? Did they only look at people within the first 5 years after infection? Would it mean something different if the EA antibodies were still detectable 20-30 years after the initial infection? Don't EA antibodies along with symptoms of the infection mean something different than EA antibodies in a patient without symptoms? Did they look at the strength/functionality of the immune systems of the healthy people with detectable antibodies compared to the immune systems of non-healthy people with detectable antibodies or healthy people without EA antibodies? Could the 20% of healthy people with EA antibodies have more active immune systems than the remaining 80% of the population? If so, it wouldn't make sense to extrapolate data about that 20% to the remaining 80% of the population. Would EA antibodies in people with less active, or even weakened, immune systems mean something different?

I could go on like this for hours. Gross over-simplification of available information, poor interpretation of that information, and extrapolation far beyond that data run rampant in medicine. Use logic, people!

 

[Snow Leopard]

Why did some people who were exposed to poliovirus get poliomyelitis while others didn't?

The severity and nature (ie what organs were ultimately infected), but these specifics don't really apply to prolonged infections. Plenty of people have latent herpesviruses, but they don't have ME.

In terms of post-polio or other similar syndromes, then it is possible that such symptoms are linked to organ or neurological damage, rather than a reactivation or latent infection.

 

[SOC]

Why did some people who were exposed to poliovirus get poliomyelitis while others didn't?

Excellent point.

IIRC, something like 0.5% of people who were infected by the poliovirus developed any sort of paralysis at all. So do we say poliovirus doesn't cause paralysis because 99.5% of the people infected with polio don't develop paralysis?

In my family, we have one person with severe paralysis (quadrapelgia) as a result of polio. We have had Hodgkin's lymphoma (associated with EBV) in at least 3 generations. We have multiple cases of ME. In previous generations, there have been a number of "mysterious" diseases. Is it beyond comprehension that even though polio, EBV, and other infections don't hit most of the population as badly as they do my family, there is likely something different (probably genetic) about the way our immune systems deal with viruses?

Not everyone who gets EBV develops MS or Hodgkin's lymphoma, both EBV-associated diseases. That doesn't mean it doesn't happen. Similarly, not everyone exposed to pathogens that seem to be associated with ME develops ME. That doesn't mean the pathogen isn't a critical component in the development of the condition. There are almost certainly other factors involved -- environmental, genetic, whatever -- but that's not news. The question is probably not whether pathogens are players, but rather what additional factors are involved in the development of ME.

 

[lansbergen]

Each virus tends to have its own signature,

But what if it is an agent of which the signature is not known?

 

[SOC]

The severity and nature (ie what parts of the body were infected), but these specifics don't really apply to prolonged infections. Plenty of people have latent herpesviruses, but they don't have ME.

So? Do we all have identical immune systems? Do we all live in identical environmental conditions? There is plenty of evidence for viruses affecting some members of the population differently than others.

EBV generally persists throughout life in most people who are infected and rarely causes any problems. In some cases, however, EBV has been linked to the development of cancers and serious conditions, including the following:

[Read on at medicinenet: The Broad Spectrum of Epstein-Barr Virus Disease]

It's a logical fallacy to suggest that since the majority of people have latent herpesviruses without developing ME, no one develops ME as a result of herpesviruses.

 

[Snow Leopard]

It's a logical fallacy to suggest that since the majority of people have latent herpesviruses without developing ME, no one develops ME as a result of herpesviruses.

If you read my previous post, I said that it begs the question as to why? There has to be more than just the virus at play, eg some sort of organ damage or immune dysfunction.

 

[halcyon]

The severity and nature (ie what parts of the body were infected), but these specifics don't really apply to prolonged infections.

Yes, but why? Why does the same exact pathogen cause such a wide variety of response in different people? This is what you have to keep in mind when you ask why the same pathogen doesn't cause ME in everybody.

In terms of post-polio or other similar syndromes, then it is possible that such symptoms are linked to organ or neurological damage, rather than a reactivation or latent infection.

The possibility for PPS to be caused by persistent, left-over poliovirus from the initial infection is still very much on the table as far as I understand. Persistence of other enteroviruses has been shown to occur in heart (causing DCM and LV dysfunction), GI tract (causing IBS and functional dyspepsia), and muscle (potentially causing abnormal lactate response to exertion). There's no reason to assume enteroviruses can't persist in the other tissues they have tropism for, namely the CNS.

 

[Snow Leopard]

Yes, but why? Why does the same exact pathogen cause such a wide variety of response in different people? This is what you have to keep in mind when you ask why the same pathogen doesn't cause ME in everybody.

We're comparing apples and oranges (acute vs chronic infections).

In terms of acute infection, luck, or stochastic factors or whatever you want to call it can affect the severity of the infection and whether key nerves (eg in poliomyelitis) are infected or not.

But for chronic infection, most cells/organs will be exposed at some time or another, but with a much lower pathogen load...

 

[SOC]

If you read my previous post, I said that it begs the question as to why? There has to be more than just the virus at play, eg some sort of organ damage or immune dysfunction.

Or a persistence of infection or reactivation that doesn't occur in all people. There is not enough evidence to settle upon or eliminate any of those theories as far as I know. Immune dysfunction could be genetic, environmental, or the result of the infection itself. Or, as you say, there could be organ or system damage.

 

[halcyon]

But for chronic infection, most cells/organs will be exposed at some time or another, but with a much lower pathogen load...

Chronic enterovirus infections are very different from other chronic infections. It's not a proviral or episomal latent infection like HIV or EBV, and it's not a chronic productive infection like HCV. What is found is the absence of productive, infectious virus, and the presence of viral RNA, in a stable, complexed dsRNA configuration. This presence of the RNA alone is enough to cause pathologic effects in tissues.