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A neuro-immune model of ME/CFS.

asleep

Senior Member
Messages
184
http://www.ncbi.nlm.nih.gov/pubmed/22718491
Metab Brain Dis. 2012 Jun 21. [Epub ahead of print]
A neuro-immune model of Myalgic Encephalomyelitis/Chronic fatigue syndrome.

Morris G, Maes M.
Source

Tir Na Nog, Pembrey, Llanelli, UK.
Abstract

This paper proposes a neuro-immune model for Myalgic Encephalomyelitis/Chronic fatigue syndrome (ME/CFS). A wide range of immunological and neurological abnormalities have been reported in people suffering from ME/CFS. They include abnormalities in proinflammatory cytokines, raised production of nuclear factor-κB, mitochondrial dysfunctions, autoimmune responses, autonomic disturbances and brain pathology. Raised levels of oxidative and nitrosative stress (O&NS), together with reduced levels of antioxidants are indicative of an immuno-inflammatory pathology. A number of different pathogens have been reported either as triggering or maintaining factors. Our model proposes that initial infection and immune activation caused by a number of possible pathogens leads to a state of chronic peripheral immune activation driven by activated O&NS pathways that lead to progressive damage of self epitopes even when the initial infection has been cleared. Subsequent activation of autoreactive T cells conspiring with O&NS pathways cause further damage and provoke chronic activation of immuno-inflammatory pathways. The subsequent upregulation of proinflammatory compounds may activate microglia via the vagus nerve. Elevated proinflammatory cytokines together with raised O&NS conspire to produce mitochondrial damage. The subsequent ATP deficit together with inflammation and O&NS are responsible for the landmark symptoms of ME/CFS, including post-exertional malaise. Raised levels of O&NS subsequently cause progressive elevation of autoimmune activity facilitated by molecular mimicry, bystander activation or epitope spreading. These processes provoke central nervous system (CNS) activation in an attempt to restore immune homeostatsis. This model proposes that the antagonistic activities of the CNS response to peripheral inflammation, O&NS and chronic immune activation are responsible for the remitting-relapsing nature of ME/CFS. Leads for future research are suggested based on this neuro-immune model.
 

justy

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Whilst this looks like an important paper that i ought to understand more of it was this part that caught my attention

Tir Na Nog, Pembrey, Llanelli, UK.

Thats not far from where i live! but i dont understand the relevance of it? As far as i am aware there is no researcg unit there or clinic.

Anyway this looks good - lets hope this research thats happening now keeps moving things forwards for us all.
Justy x
 

SarahLaBelle

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Oak Park, IL USA
Whilst this looks like an important paper that i ought to understand more of it was this part that caught my attention

Tir Na Nog, Pembrey, Llanelli, UK.

Thats not far from where i live! but i dont understand the relevance of it? As far as i am aware there is no researcg unit there or clinic.

Anyway this looks good - lets hope this research thats happening now keeps moving things forwards for us all.
Justy x

I found Pembrey, read its postal town is Llanelli, in Wales. But I can make no sense of Tir Na Nog. Is that yet a smaller town than Pembrey?

Seems to be the location of the first author, whoever that is.
 

Glynis Steele

Senior Member
Messages
404
Location
Newcastle upon Tyne UK
I found Pembrey, read its postal town is Llanelli, in Wales. But I can make no sense of Tir Na Nog. Is that yet a smaller town than Pembrey?

Seems to be the location of the first author, whoever that is.

Tir Na Nog is from Celtic(Irish) Mythology - "Land of the Young". The author is, as George above said, Ger.

http://en.wikipedia.org/wiki/Tír_na_nÓg
 

Enid

Senior Member
Messages
3,309
Location
UK
No we are not floydguy (still looking) but Prof Michael Maes has a long involvement working for ME. Originally from the Netherlands opposed the psychiatric modelists and apparently left. (All can be googled). Be nice to know who G Morris is too.
 

jeffrez

Senior Member
Messages
1,112
Location
NY
Our model proposes that initial infection and immune activation caused by a number of possible pathogens leads to a state of chronic peripheral immune activation driven by activated O&NS pathways that lead to progressive damage of self epitopes even when the initial infection has been cleared. Subsequent activation of autoreactive T cells conspiring with O&NS pathways cause further damage and provoke chronic activation of immuno-inflammatory pathways. The subsequent upregulation of proinflammatory compounds may activate microglia via the vagus nerve. Elevated proinflammatory cytokines together with raised O&NS conspire to produce mitochondrial damage.

Doesn't sound like anything too new... and doesn't sound good! ;-)

These kinds of immune abnormalities, inflammatory cytokines, T & B cell reactivities, etc. seemingly would be SO easy to test for & differentiate from the normal population. How many years are researchers just going to repeat this stuff over and over without proposing all the immune dysfunction as at least some kind of biomarker?
 

Bob

Senior Member
Messages
16,455
Location
England (south coast)
I believe that Gerwyn Morris is an ME patient, and used to be a member of this forum, under the username 'Gerwyn'.
I believe Gerwyn left this forum to help set up another patient forum about a year ago, and then left that forum to help set up yet another forum.
I don't know anything else about him, except that he is a (very) passionate advocate for the biomedical model of ME.
 

Mula

Senior Member
Messages
131
There is no other explanatory model for ME/CFS. This is the only paper to have done that. How would suggest it is not new?
 

justy

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I think the ideas nehind the paper are not new ideas, but have been brought together into a cohesive model - will need to read the full paper and mull it over for a bit.

I agree that what we need to see is biomarkers, not just more ideas.

I know who Gerwyn is by both indirect experience and reputation. I had no idea we lived in the same county - virtually neighbours by world standards.

This is the second paper i have seen that patients were involved in. Wasn't the other one Maes with Cort?
I wonder what the rationale is behind this. Not saying it;s a bad thing, but what does it all mean?

I also wonder if i can get My GP to read this seeing as it's publisehed as originating in his home county :)

All the best, Justy.
 

Bob

Senior Member
Messages
16,455
Location
England (south coast)
I think the ideas nehind the paper are not new ideas, but have been brought together into a cohesive model - will need to read the full paper and mull it over for a bit.

I agree that what we need to see is biomarkers, not just more ideas.

Yes, from the abstract, it looks like a 'review' paper, rather than original research.
Nothing wrong with that though. Published reviews can be extremely helpful and influential.
 

Mula

Senior Member
Messages
131
I am reading the paper and it is a genuinely an authentic explanatory model as opposed to a review. Other researchers have looked at elements of the pathology, but none of those papers have produced a detailed model for the cause of the relapsing remitting nature or the worsening of symptoms in the form of PEM.
 

George

waitin' fer rabbits
Messages
853
Location
South Texas
(tail wags) I like the fact that those who know Ger, know Ger and those who don't, that's even better.(big grins)

The paper is good from a couple of points of view. One it gets out some very new terms such as "Neuroimmune' and PENE (not directly) which are new words that will need to enter into the lexicon in order for doctors and researchers to understand the illness better. It's turning out to be a complicated illness with a lot of components or maybe even a spectrum of illness. But anyway ya slice it, it's gonna need some new terms for docs to be able to get their heads around it all.

Ger and I go back to the beginning, when I used to fetch his slippers and bring him his newspaper. (grins) One thing you can count on is that Gerwyn is intellectually brilliant. There are other things that Ger is as well but. . . and If ya put us in a room together I'd probably end up taking a bite out of his ass (he could use a little less of it from time to time) and grin while doing it but I wouldn't mess with his brain.

I think some in the community are a little confused that the guy who used to beat everyone over the head with the HGRV model is now involved in a different potential model for the illness. (I don't think a retro-viral model is mutually exclusive to autoimmunity in general but I do believe that HGRV's won't prove to be the smoking gun for us.) This illness is turning out to be rather complicated for example; I was recently reading a paper on how Herpes virus' 1 and 2 use Calcium ions to stop the cells production of energy. The virus' then use the energy created by the cell to replicate and move to another cell where they kill another cell by using a calcium ion and steal that cells energy and so forth and so on. Many of the cells don't recover, some do. It won't kill ya but you will work at a very reduced capacity. That's just one example of the some of the research that' could very well be applied to this illness and It's a very good basis for the type of mitochondria based fatigue that many ME patients experience on a day to day basis. It's way more complicated than a straight up viral infection where Agent A causes Symptom(s) B. While a retroviral model ties many of the aspects of ME up nicely and a MLV type retrovirus is even better, we still have to deal with the problem of inadequate technology and the time it takes to bring retroviral research to some solid conclusions.Meanwhile there is some very good research out there that could help us get treatments and respectability. This paper pulls some of those parts together and presents them coherently.

Now in the are of mito damage, Ger has been exploring this aspect of ME for a long time due to his following of Dr. Myhills protocol. So teaming up with Micheal Maes to do a hypothesis paper that looks at this and other aspects of the illness is a good use of his brain cells. (big grins)

Hypothesis generation is an important part of the research process. There is a whole area of medicine devoted to this pursuit, in fact it has it's own journal The Journal of Medical Hypotheses! Going over current research, culling false starts and dead ends and then pulling together a hypotheses based on a body of work that can then be the basis of new research work is a very necessary part of moving research forward. This paper looks pretty good, its got some good stuff to back it up and points in some good directions for future research. More importantly it pulls together the very scattered bits of research and illustrates the complexity of ME that has stymied research and treatments and doctors attitudes for the last 30 years. (among other things that have stymied research, grins)

Anyway them is my two thoughts on the paper. (big grins)
 

Mula

Senior Member
Messages
131
A range of pathogens cause autoimmunity, but as an example mitochondria toxicity does not result from that a failure to recognize. The final diagram has this as a consequence of the pathology.

I am trying to compare PENE and PAR. Are they the same?

"a pathological inability to produce sufficient energy on demand with prominent symptoms primarily in the neuroimmune regions."
http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2796.2011.02428.x/full

"Insignificant increases in physical activity or minor cognitive tasks may exacerbate immune dysfunction, inflammation and O&NS thereby producing further signs of the disease (Twisk and Maes 2009). The effect may be delayed, but is predictable and accumulative, varying in duration dependant on disease severity and accumulative activity levels (VanNess et al. 2010; Van Oosterwijck et al. 2010; Carruthers et al. 2011)."
 

floydguy

Senior Member
Messages
650
(tail wags) I like the fact that those who know Ger, know Ger and those who don't, that's even better.(big grins)

I think some in the community are a little confused that the guy who used to beat everyone over the head with the HGRV model is now involved in a different potential model for the illness. (I don't think a retro-viral model is mutually exclusive to autoimmunity in general but I do believe that HGRV's won't prove to be the smoking gun for us.) This illness is turning out to be rather complicated for example; I was recently reading a paper on how Herpes virus' 1 and 2 use Calcium ions to stop the cells production of energy. The virus' then use the energy created by the cell to replicate and move to another cell where they kill another cell by using a calcium ion and steal that cells energy and so forth and so on. Many of the cells don't recover, some do. It won't kill ya but you will work at a very reduced capacity. That's just one example of the some of the research that' could very well be applied to this illness and It's a very good basis for the type of mitochondria based fatigue that many ME patients experience on a day to day basis. It's way more complicated than a straight up viral infection where Agent A causes Symptom(s) B. While a retroviral model ties many of the aspects of ME up nicely and a MLV type retrovirus is even better, we still have to deal with the problem of inadequate technology and the time it takes to bring retroviral research to some solid conclusions.Meanwhile there is some very good research out there that could help us get treatments and respectability. This paper pulls some of those parts together and presents them coherently.

Anyway them is my two thoughts on the paper. (big grins)

Thanks for your thoughts. I admit I was struck by the lack of content around HGRVs. Gerwyn seems like a smart guy but can come across as really arrogant and condescending if you end up on the other side of the argument with him.