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

[Hip]

Good way of putting it.

I hardly think that @adreno saying "biological systems are complex and dirty" offers any useful criticism of the sickness behavior / vagus nerve infection theory of ME/CFS.


I often tend to be on the "what if" speculative side of the scientific spectrum, happy to entertain an interesting hypothesis, rather than on the conservative, skeptical side (although I can change hats when necessary).

But I do appreciate good criticism and fault finding, especially if it can neatly demolish a hypothesis, because that can be very useful: it then saves me time and effort, as I no longer have to go down the road of that particular hypothesis.

But so far I cannot see anything in the criticisms provided that even puts a dent in the sickness behavior / vagus nerve infection theory.

 

[adreno]

I hardly think that @adreno saying "biological systems are complex and dirty" offers any useful criticism of the sickness behavior / vagus nerve infection theory of ME/CFS.

I think you missed the point. Those cytokines you mention are non-specific, and not biomarkers of "sickness behavior" (SE), nor ME. It is not so that elevation of these cytokines specifically indicates SE, same as the absence of elevation of these does not preclude it. In fact you cannot diagnose SE. It is really just some psych term describing a set of behaviors. You can try to statistically approximate the cytokine pattern involved, but that doesn't make it specific. Any theory that tries to define ME as SE is therefore unspecific (i.e., useless). I think the term Prof. Edwards coined - "immunobabble" - is very fitting here.

 

[MeSci]

Of course. Estimates vary but generally speaking for each case of Lyme disease recorded in the UK you get like 100-300 cases in Central European places such as Austria, Slovenia, Germany, Poland etc. where you get bitten by ticks pretty much every time you go hiking (only slight exaggeration) and a high percentage of them (relatively speaking) are infected with Borrelia and other pathogens. Viral meningitis is very common after a tick bite, I knew several people who got this.

Sorry if this has already been said - I am way behind on this thread! - but maybe to get ME you need Lyme/borrelia/other infection/cause plus something else, for it to become chronic/neurological/whatever, e.g. factors that I mentioned earlier - co-infections, malnutrition/nutritional deficiency, over-exertion, stress, etc.

Could people in endemic countries even have developed a degree of immunity to borrelia?

 

[Sidereal]

Sorry if this has already been said - I am way behind on this thread! - but maybe to get ME you need Lyme/borrelia/other infection/cause plus something else

That would be my feeling too.

Could people in endemic countries even have developed a degree of immunity to borrelia?

I have no idea.

 

[Hip]

I think you missed the point. Those cytokines you mention are non-specific, and not biomarkers of "sickness behavior" (SE), nor ME. It is not so that elevation of these cytokines specifically indicates SE, same as the absence of elevation of these does not preclude it. In fact you cannot diagnose SE. It is really just some psych term describing a set of behaviors. You can try to statistically approximate the cytokine pattern involved, but that doesn't make it specific. Any theory that tries to define ME as SE is therefore unspecific (i.e., useless). I think the term Prof. Edwards coined - "immunobabble" - is very fitting here.

I believe it is you that missed the point, which I covered earlier. Let me explain this point again for you:

I agree that those three cytokines cannot be used as blood biomarkers of sickness behavior (except perhaps for IL-6). I stated earlier that secreted IL-1β only travels short distances to adjacent cells. It does not really travel well throughout the blood and body. It has a limited range. So overall blood levels of IL-1β cannot tell you anything about the levels of IL-1β at specific locations in the body.

IL-1β can be very high in certain locations in the body, but because IL-1β does not travel far in the blood, any blood test will not show high levels of IL-1β overall.

Are you with me so far?


So, if the vagus nerve was locally infected, there could be extremely high levels of IL-1β within that nerve (triggering sickness behavior), yet a blood test would not show any significant increase in overall IL-1β levels.

Think about that in the context of the vagus nerve infection theory.

So yes I am agreeing with you that blood IL-1β is not really an overall biomarker for sickness behavior, but please try to see the point I am making.

In fact you cannot diagnose SE. It is really just some psych term describing a set of behaviors.

Of course you can. Sickness behavior kicks in automatically when you come down with a nasty bug like the flu, or a gastrointestinal infection, etc. Sickness behavior is easy to observe and diagnose in these cases. In fact it is sometimes only through our sickness behavior response do we realize we have come down with an infection.

Sickness behavior involves: fatigue, fever, malaise, lethargy, depression, anhedonia, cognitive impairment.

Sickness behavior is not really a psychiatric term; it is a term used in the study of infections.

The overall mental feeling you get during these infections is roughly the same (apart from pathogen-specific bodily symptoms like chest congestion or diarrhea). That's because infections activate the same sickness behavior mechanism, which is an a built-in response in the brain.


The cytokine triggers of sickness behavior are detailed in papers like the following one:

Cytokine, Sickness Behavior, and Depression

 

[Valentijn]

But what we have is evidence of absence - at least in comparison to normal people with available test - another non-sequitur I think!

Well, the whole point for it not equating to "evidence of absence" is that there are certainly things which are not tested for. There are probably a great many problems, infectious or otherwise, which we simply do not yet have the technology to detect, or have not done the research. This has happened repeatedly throughout history, and has been used to diagnose MS, ulcers, and a great many of other things as not being biological illnesses, due to an absence of evidence to the contrary.

The other problem is that UK patients simply do not get tested once they are labeled with ME. They get treated for a psychosomatic disorder, and are usually managed by doctors in a way which is aimed at minimizing their contact with biomedical practitioners. How the hell are doctors supposed to find something when they're being brainwashed into not looking for it in the first place?

Until "absence of evidence" isn't primarily attributable to a lack of individual or group research, it's extremely premature to conclude that it indicates "evidence of absence". And even then there will always be uncertainty due to imperfect or as-yet undeveloped diagnostic methods.

 

[Valentijn]

Haha, I just looked up Esther Crawley, one of the doctors Prof. Edwards mentioned as being located near the New Forest, and found that she supervised a trial of the Lightning Process in children with ME (the completely inappropriately named SMILE study).

Yes, if she had patients potentially exposed to Lyme, she'd focus her efforts on disabusing them of the notion. She is a firmly entrenched proponent of psychosomatic theories, and would not seriously investigate potential infections, even if there was a strong indication.

Many parents have complained that when their children with ME remain ill after CBT/GET, she declares that they actually have been cured, and gives them a new diagnosis of pervasive refusal syndrome. Her failure to find, notice, or report infections does absolutely nothing to support the suggestion of a lack of infections.

 

[adreno]

Could people in endemic countries even have developed a degree of immunity to borrelia?

Certainly. Evolution would take care of that, given enough time.

 

[Sidereal]

I agree that those three cytokines cannot be used as blood biomarkers of sickness behavior (except perhaps for IL-6). I stated earlier that secreted IL-1β only travels short distances to adjacent cells. It does not really travel well throughout the blood and body. It has a limited range. So overall blood levels of IL-1β cannot tell you anything about the levels of IL-1β at specific locations in the body.

IL-1β can be very high in certain locations in the body, but because IL-1β does not travel far in the blood, any blood test will not show high levels of IL-1β overall.

Hip, have you seen the recent Lipkin/Hornig cerebrospinal fluid cytokine study? IL-1β was lower in ME/CFS than in MS patients and normal controls. IL-6 was almost undetectable in ME/CFS.

 

[adreno]

Sickness behavior involves: fatigue, fever, malaise, lethargy, depression, anhedonia, cognitive impairment.

With the exception of fever, those behaviors are pretty damn unspecific and not conclusively indicative of infection. So all you have is no biomarkers, and a handful of unspecific behaviors. That's your model of ME?

 

[Hip]

Hip, have you seen the recent Lipkin/Hornig cerebrospinal fluid cytokine study? IL-1β was lower in ME/CFS than in MS patients and normal controls. IL-6 was almost undetectable in ME/CFS.

I did see that one, thanks.

Though I believe they found IL-1β and TNF-α were elevated in the cerebrospinal fluid, rather than reduced.


But for the reasons I mentioned above, the overall level of IL-1β in the cerebrospinal fluid or blood would have no bearing on the level of IL-1β in the vagus nerve. In fact there is no direct link between most of the vagus and the areas where cerebrospinal fluid flows (ie, brain and spine).

So locally within the vagus nerve, there could be very high level of IL-1β, yet this would not have any bearing on blood or CSF level of IL-1β.

The fact that IL-1β and TNF-α are elevated in the cerebrospinal fluid, though, does suggest that these cytokines might be contributing to the activation of sickness behavior.

Any of the three cytokines IL-1β, TNF-α and IL-6 can activate sickness behavior when they are either release in the brain, or are in the blood that courses through the arteries in the brain.

I believe it is only IL-1β however that can trigger the vagus nerve to activate sickness behavior.

 

[Hip]

With the exception of fever, those behaviors are pretty damn unspecific and not conclusively indicative of infection. So all you have is no biomarkers, and a handful of unspecific behaviors. That's your model of ME?

What are you on about @adreno?

You seem to be struggling to comprehend sickness behavior.

 

[adreno]

What are you on about @adreno?

You seem to be struggling to comprehend sickness behavior.

Well, I'm certainly struggling to comprehend why you find it so interesting. Sickness behavior can be observed in cancer for example:

Sickness behavior resulting from cytokine release may provide a framework to explain many cancer-related symptoms, including depression, cognitive impairment, cachexia, fatigue, and a component of pain perception.

And as far as we know, this is not an infectious disease. Autoimmune diseases are also associated with sickness behavior:

Other autoimmune diseases are associated with fatigue and sickness behavior including rheumatoid arthritis and systemic lupus ery- thematosus (SLE)8 and perhaps most notably multiple sclerosis (MS).

Even Major Depressive Disorder has been proposed to be sickness behavior.

So I fail to see what these observed behaviors can tell us about ME. They will certainly not tell us whether ME is infectious or autoimmune, which I believe is the topic of this thread.

 

[Sidereal]

I did see that one, thanks.

Though I believe they found IL-1β and TNF-α were elevated in the cerebrospinal fluid, rather than reduced.

Nope, here's a screenshot from the paper in question:

TNF-a wasn't presented in a figure but the table says there was a non-significant statistical trend toward lower score in the ME/CFS group compared to controls.

 

[SunMoonsStars]

Speaking of Vagus Nerve
There is a doctor who was treating MS and others that had CCSVI and in turn he found that it was not the blockages of the veins that were helping patients but the affect it had on the Vagus nerve. CCSVI is being shown to be caused by multiple infections building up and forming plaques on the inside of the jugular veins and those run along side the Vagus Nerve. Its all interesting but non of it helps with the idea of what comes first and why some of us battle the ongoing rotating chronic infections that are acute as well as ongoing fatigue and other symptoms for years on end.
http://autonomicspecialists.com

 

[Hip]

So I fail to see what these observed behaviors can tell us about ME.

Have you actually read Michael VanElzakker's vagus nerve infection hypothesis? Or any of the threads where this paper is discussed? You are arguing against this hypothesis, yet you don't seem to really understand it.

I'll try again to explain:

Michael VanElzakker hypothesizes that many of the symptoms of ME/CFS simply arise out of sickness behavior. In other words, our ME/CFS symptoms are sickness behavior. Sickness behavior and ME/CFS symptoms are one and the same. I am going for reiterative overkill here to get the point across!

The fact that sickness behavior symptoms also appear in cancer and other diseases actually helps prove the point: because the fatigue, brain fog, etc symptoms in these other diseases like cancer are very similar to ME/CFS. So that kind of helps demonstrate the assertion that VanElzakker is making: that sickness behavior symptom and ME/CFS symptom are one and the same.


The only difference between cancer and ME/CFS is the cause / trigger of sickness behavior. In ME/CFS, it is cytokines induced by chronic vagus infection that triggers sickness behavior (or so the assertion goes); in cancer it is cytokines induced by the tumor that triggers sickness behavior.

It does not make any difference where the cytokines comes from; infection, tumor, autoimmunity. All that matters is that the cytokines are of the type that are known to activate sickness behavior.

 

[Hip]

Nope, here's a screenshot from the paper in question:

Would you have a link to that paper please?

The article I read on Lipkin's research said:

Lipkin’s team also found differences in cerebrospinal fluid biomarkers between patients and controls.

Patients had elevated levels of the TH-2 type cytokines IL-10 and IL-13 and elevated levels of four TH-1 cytokine: IL-1 beta, TNF-alpha, IL-5, and IL-17.

 

[Sidereal]

Would you have a link to that paper please?

The article I read on Lipkin's research said:

Well full text is behind a paywall.

The PR article you linked is from 2013. This study is from 2015.

http://www.nature.com/mp/journal/vaop/ncurrent/full/mp201529a.html

 

[Hip]

The PR article you linked is from 2013. This study is from 2015.

Thanks for the link.

Lipkin informally released his research results a long time before his paper was actually published. That's why there were articles like the one I read, even though no paper was yet available at the time. However, it's possible I guess that the article might have got it wrong.

I just found this very similar Feb 2015 ME/CFS cytokine paper by Lipkin, Hornig, Klimas, Montoya et al. If you look at Fig 1 of that study, they found IL-1β raised in for short-duration ME/CFS, and reduced for long-duration ME/CFS. However, that was in the blood, not cerebrospinal fluid.

 

[Hip]

Speaking of Vagus Nerve
There is a doctor who was treating MS and others that had CCSVI and in turn he found that it was not the blockages of the veins that were helping patients but the affect it had on the Vagus nerve. CCSVI is being shown to be caused by multiple infections building up and forming plaques on the inside of the jugular veins and those run along side the Vagus Nerve. Its all interesting but non of it helps with the idea of what comes first and why some of us battle the ongoing rotating chronic infections that are acute as well as ongoing fatigue and other symptoms for years on end.
http://autonomicspecialists.com

That's interesting. Would you have a link to any studies or articles which detail these infection-derived plaques on the inside of the veins that run alongside the vagus nerve?