Do MEs cause CFS?

[lansbergen]

Which paper caught your eye Lansbergen... ??

http://www.sciencedirect.com/science/article/pii/S1567724913002390

 

[mellster]

You said exertion reduces appetite, could you clarify how and why please? It's new information to me so, I am curious....

http://www.sciencedaily.com/releases/2008/12/081211081446.htm

I don't know if there are any other or more recent studies on this.

 

[Snow Leopard]

Modest exertion increases my appetite and I dare say it does for others too, making it hard for some to lose weight from exercising if their diet is not under control...

 

[Leopardtail]

http://www.sciencedaily.com/releases/2008/12/081211081446.htm

I don't know if there are any other or more recent studies on this.

Look forward to checking that out, thanks....

 

[Jonathan Edwards]

The paper reported increased latent replication of EBV, lower cytokine response against EBV, and reduced number of EBV antibody producing cells. I'm all for being cautious to make hasty conclusions, but it seems very unlikely to me (as amateur) that this could be a positive adaption (or mere chance).
I hope these findings are replicated soon.

It also fits with Rituximab, and mononucleosis often triggering CFS.

My understanding of her presentation at IiME this year was that the difference is much more subtle and specific, and it was the specificity of the antibody response that was so interesting. As I have said before, (as the guy who started all this rituximab stuff) I cannot see that it fits with rituximab in a meaningful way. So, as indicated on the other EBV test thread, I am in favour of looking for a more subtle analysis. And there are lots of examples where briskness of immune response to micro-organisms is actually disadvantageous - second dose Dengue fever being the classic case.

 

[Leopardtail]

My understanding of her presentation at IiME this year was that the difference is much more subtle and specific, and it was the specificity of the antibody response that was so interesting. As I have said before, (as the guy who started all this rituximab stuff) I cannot see that it fits with rituximab in a meaningful way. So, as indicated on the other EBV test thread, I am in favour of looking for a more subtle analysis. And there are lots of examples where briskness of immune response to micro-organisms is actually disadvantageous - second dose Dengue fever being the classic case.

Is that issue purely briskness of response, or is there an element of over-response?
Just asking out of curiosity....

 

[Jonathan Edwards]

Is that issue purely briskness of response, or is there an element of over-response?
Just asking out of curiosity....

Briskness was probably not the best word - I meant in the sense of 'over-response' with multi-organ system failure.

 

[lansbergen]

I meant in the sense of 'over-response' with multi-organ system failure.

That is much clearer for me.

 

[MeSci]

Modest exertion increases my appetite and I dare say it does for others too, making it hard for some to lose weight from exercising if their diet is not under control...

There seems to be good evidence that exercise plays little or no part in weight reduction. It's obviously healthy, if done by people who can tolerate it, at an appropriate level.

But some of us here have lost weight easily through cutting out gluten, and also then reducing sugar and grain intake. My weight started falling off effortlessly when I ditched gluten - completely unintended, unexpected and very welcome! I also rebuilt muscle without exercising, presumably thanks to the diet and supplements.

I think we are getting a bit off topic...

 

[Leopardtail]

Briskness was probably not the best word - I meant in the sense of 'over-response' with multi-organ system failure.

Thanks both for the clarification the reminder that my lot is not so bad after all!!

So if I now understand you the response is both amplified and non-specific?

 

[thegodofpleasure]

I think we need to get the context right here. Remember that almost everyone has persistent EBV infection of B cells. It is the normal situation for at least 90% of human beings. The piece on Dr Pender's theory looks to me naive. I have never heard of this theory and frankly it does not make much sense, since all our B cells contain EBV DNA. The case report he gives tells us nothing I am afraid. His ideas about rheumatoid arthritis similarly do not seem to make sense since EBV DNA is everywhere in all of us.

Carmen Scheibenbogen has done some extremely interesting work on altered EBV serology in CFS patients. I do not think one can call this an impaired response, because we do not know its significance. it might be a 'better' response for all we know. But the fact that it is different certainly suggests that B cell regulation may be shifted in some way. It may be shifted for responses to all sorts of other things. I don't think we know. At least it is another piece of evidence for a change in B cell behaviour.

I do not think any of this indicates that 'EBV plays a role'. Since we all have EBV it is hard to say it is the cause of ME in PWME when other people have EBV and no ME. What is a more interesting question is whether the causation of some ME needs EBV to keep itself going. If it does then eradicating EBV would make sense. However, Dr Pender's idea that rituximab produces improvement by eradicating EBV must I think be nonsense because of the time frame of response - as we have discussed before. What is conceivable is that in those who stay well the absence of EBV contributes to that. The question then is why the other people relapse if their EBV is cleared as well?

I cannot see much point in T cell immunotherapy if we can get rid of the B cells with rituximab much more effectively!!!

@Jonathan Edwards Thankyou for your thoughts.

It seems to me that the role of EBV in diseases such as M.E. is probably via epigenetic modification of immune function i.e. beyond the changes it routinely causes in order to perpetuate itself. Such an epigenetic process would explain why it is that only the sick people become ill.

On that point, I found this interesting: "Host epigenetic modifications by oncogenic viruses" http://www.nature.com/bjc/journal/v96/n2/pdf/6603516a.pdf

and this: "Epstein-Barr Virus Latency in B Cells Leads to Epigenetic Repression and CpG Methylation of the Tumour Suppressor Gene Bim" http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1000492

 

[Snow Leopard]

I for one don't really follow the 'chronic EBV' hypothesis either, as there are many people with what appears to be classic ME who have never had an EBV infection.

So the disease is not specific to EBV, but at the same time EBV is one of, if not the most common trigger and perhaps risk factor, so it is fair to ask what could be going wrong.

We know that EBV specifically targets B Cells through the CD21 receptor and EBV infections tend to persist much longer than most viral infections and it is quite possible that this may lead to epigenetic changes being induced over time as a response.

I am reminded of the following paper, if perhaps slightly inappropriately named (that's what you get when a bunch of Physicists write a CFS paper):
Can persistent Epstein-Barr virus infection induce chronic fatigue syndrome as a Pavlov reflex of the immune response?
http://www.ncbi.nlm.nih.gov/pubmed/22873615
It has more to do with modeling of the kinetics of onset and relies on a couple specific factors found by others (I really need to re-read it to explain it properly, but I'm just putting it out there)

There are also papers like this one, but I'm not sure what to make of it:
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0085387

Oh and in terms of fashion, the current Avant-garde:
A thermodynamic perspective of immune capabilities.
http://www.ncbi.nlm.nih.gov/pubmed/2182448
http://arxiv.org/pdf/1105.3146.pdf
I'd be interested to hear what people think about the above paper...

 

[heapsreal]

I for one don't really follow the 'chronic EBV' hypothesis either, as there are many people with what appears to be classic ME who have never had an EBV infection.

So the disease is not specific to EBV, but at the same time EBV is one of, if not the most common trigger and perhaps risk factor, so it is fair to ask what could be going wrong.

We know that EBV specifically targets B Cells through the CD21 receptor and EBV infections tend to persist much longer than most viral infections and it is quite possible that this may lead to epigenetic changes being induced over time as a response.

I am reminded of the following paper, if perhaps slightly inappropriately named (that's what you get when a bunch of Physicists write a CFS paper):
Can persistent Epstein-Barr virus infection induce chronic fatigue syndrome as a Pavlov reflex of the immune response?
http://www.ncbi.nlm.nih.gov/pubmed/22873615
It has more to do with modeling of the kinetics of onset and relies on a couple specific factors found by others (I really need to re-read it to explain it properly, but I'm just putting it out there)

There are also papers like this one, but I'm not sure what to make of it:
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0085387

I dont think anyone is saying ebv is the cause of cfs/me but can be a common trigger and also can be an ongoing infection for many due to a dysfunctional immune system. Current testing is inadequate to be able to tell if an ebv infection is a past infection or a reactivated infection.

These type of infections commonly reactivate in immune suppressed people, cfs/me are immune supressed with the low nk function, nk cells fight viruses and cancer cells, recent research has also found its quite common to also have low cd8 t cell function in cfs/me, this also is an important role in fighting ebv. Recent research into MS is showing this is an issue and is allowing ebv to reactivate. Treating cd8 t cells with ebv vaccines are showing very positive responses to this type of treatment. This may shoot the theory of MS being an auto immune illness.

I dont quite believe that many people with ME have never had ebv( small majority), when most info on ebv says the majority of people have ebv. This issue again comes down to testing unable to show if these viruses are reactivating. Also there is a common finding with some cfs/me people being infected with ebv and producing igg life long antibodies and years later testing showing none of these life long antibodies being present. This is a finding that has occurred in me and it was also a common finding in many cfsers involved in the lake tahoe epidemic in the 1980s. I believe B cells make antibodies to ebv, so maybe a subgroup have a dysfunction here in making antibodies. Maybe very similar to recent findings in MS who have cd8 t cells which arent able to fight ebv??

I guess while they cant prove 100% its an issue in cfs/me, neither can they prove it isnt an issue in cfs/me. Theres just too little known about ebv. As dr peterson and klimas have said, ebv is just one of these infections that always keeps popping up in research that it just cant be ruled out yet. Again maybe a sub group and maybe bigger then we think??

 

[Jonathan Edwards]

Thanks both for the clarification the reminder that my lot is not so bad after all!!

So if I now understand you the response is both amplified and non-specific?

The immune reaction is life threatening. It probably has a very specific mechanism but like anaphylaxis hits multiple organ systems.

 

[Leopardtail]

The immune reaction is life threatening. It probably has a very specific mechanism but like anaphylaxis hits multiple organ systems.

Tx for the clarification.

 

[Jonathan Edwards]

@Jonathan Edwards Thankyou for your thoughts.

It seems to me that the role of EBV in diseases such as M.E. is probably via epigenetic modification of immune function i.e. beyond the changes it routinely causes in order to perpetuate itself. Such an epigenetic process would explain why it is that only the sick people become ill.

On that point, I found this interesting: "Host epigenetic modifications by oncogenic viruses" http://www.nature.com/bjc/journal/v96/n2/pdf/6603516a.pdf

and this: "Epstein-Barr Virus Latency in B Cells Leads to Epigenetic Repression and CpG Methylation of the Tumour Suppressor Gene Bim" http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1000492

We have known for many decades that for all of us, meeting EBV causes a permanent change in the way our B cells behave. It does not seem to matter much but you can show it in tissue culture. I forget the detailed mechanism but our B cells carry EBV DNA. I think it would have been predicted that some form of long term activation or deactivation of promoter regions on various human genes must occur. It sounds as if this is now being tracked down in detail. I suspect this is part and parcel of how the virus perpetuates itself - otherwise it would not bother to do this trick.

I am not sure what 'epigenetic' adds here. In the titles of the two papers the word epigenetic could have just been gene, although there might be some merit in having a catch all term for methylation and histone alterations.

And I am not sure how this would explain why some people get ill and others do not. The permanent effect on B cells seems to happen to all of us.

 

[thegodofpleasure]

I for one don't really follow the 'chronic EBV' hypothesis either, as there are many people with what appears to be classic ME who have never had an EBV infection.

So the disease is not specific to EBV, but at the same time EBV is one of, if not the most common trigger and perhaps risk factor, so it is fair to ask what could be going wrong.

@Snow Leopard I don't think that EBV causes M.E. directly either, but it may well be responsible for causing certain epigenetic changes which could enable M.E. to develop in a predisposed patient group. (See my earlier post #211)

I'm also mindful that the effects of EBV should not be viewed in isolation - excessive antibiotic use early in life, changes in gut flora / microbiota, chemical exposures, etc could all conspire / compound the problem.

The reason why I raised the issue of EBV, was to question whether it could be a factor in certain M.E. subgroups but not others.

 

[thegodofpleasure]

Here's a link to a very useful 2007 article from "Nature" on the influence of Epigenetics in human disease : https://app.box.com/s/gfva4qghlngt8hv3xebg

Phenotypic plasticity and the epigenetics of human disease
Andrew P. Feinberg
"It is becoming clear that epigenetic changes are involved in human disease as well as during normal development. A unifying theme of disease epigenetics is defects in phenotypic plasticity — cells’ ability to change their behaviour in response to internal or external environmental cues. This model proposes that hereditary disorders of the epigenetic apparatus lead to developmental defects, that cancer epigenetics involves disruption of the stem-cell programme, and that common diseases with late-onset phenotypes involve interactions between the epigenome, the genome and the environment. Increased understanding of epigenetic-disease mechanisms could lead to disease-risk stratification for targeted intervention and to targeted therapies."

 

[Jonathan Edwards]

Oh and in terms of fashion, the current Avant-garde:
A thermodynamic perspective of immune capabilities.
http://www.ncbi.nlm.nih.gov/pubmed/2182448
http://arxiv.org/pdf/1105.3146.pdf
I'd be interested to hear what people think about the above paper...

It seems a bit like mathematically modelling the complex system dynamics of a termite colony without actually ever having seen a termite colony. To my mind, it is reasonably easy to understand how autoimmunity comes about if one has a detailed knowledge of how the various cells behave and understands simple ideas like positive feedback, random gene shuffling, and natural selection. You don't need any weird equations with Greek symbols - we didn't have any in our 1999 Immunology paper. They have a very odd idea of autoimmunity, apparently based on some rare variety I have never heard of. The idea that we can understand things in terms of complex systems dynamics is fair enough but I rather feel 'been there, done that'.

 

[Leopardtail]

Well I am the complete opposite, I pick up everything going and it makes me very unwell. Last winter I had 8 separate viruses/infections including Norovirus but I do have an explanation for this now having recently tested positive on an LTT Borrelia Immunoblot done through Infectolab Germany. Also I have a co-infection and my immune system is over-reacting to many different viruses so actually I don't even have ME/CFS, I have been wrongly diagnosed for 14 years so perhaps I shouldn't be joining in with the discussion which I am finding fascinating.

By the way @Jonathan Edwards after going on the facebook UK Lyme's site I am not at all convinced that chronic Lyme disease is that rare because practically all of them were originally diagnosed with ME/CFS and new people (often quite young) are appearing daily and getting very little help from the NHS. From the reading I have done it would seem it isn't just deer ticks that carry infection, it can be any biting insect. If only that was accepted by the powers that be we might get some different answers and even some treatment on the NHS!

(I have chosen to go the herbal route with a Lyme literate herbalist in the hope I can rebuild my broken immune system).

One other thing I would like to throw in is that Dr Horowitz in the UK who has written a great book on all things Lyme talks about a multisystems immune dysregulation which not only involves multiple infections, viruses but also heavy metal poisoning, poor detoxification systems, genetic polymorphisms and finally yeasts and molds. His conclusion that all of the above can be involved in illnesses like CFS/ME has come from seeing and testing thousands of patients who indeed test positive for heavy metal poisoning, usually mercury and/or lead, as well as positive for things like borrelia and co-infections and yeast/mold infections so I think these issues are often overlooked when talking about ME/CFS. Indeed mercury and nickel poisoning were the first real abnormalities that I tested positive for and started off this very long journey which began for me in 2000.

Pam

Ditto when my ME was severe.