Theoretical Immunology

[Leonard]

in order to keep this thread as complete as possible, from http://www.thisisms.com/forum/general-d ... 23331.html:

Just found this interesting remedy, "Gene Eden" that claims to remove latent EBV from the body:

http://www.prweb.com/releases/2014/01/prweb11462653.htm

http://www.buy-gene-eden.com/EBV.php

gainsbourg

very interesting...
any reports about experiences ?

I have a very high load of Epstein-Barr antigens (Epstein-Barr IgG around 20 is normal vs 348 for myself!!);
and a very high load of Herpes simplex antigens (normal Herpes simplex IgG is <0.9 vs 20.9 for myself!!);
but my gut is ok, at least it is not leaking (from standard test on the basis of organic urine metabolites).
I am sure the EBV causes my MS.

the webpage also suggests a link with Hepatitis.
this is very remarkable because I was vaccinated for Hepatitis just a few years before the outbreak/diagnosis of my MS and - I guess - the EBV/Herpes/Hepatitis load of antigen....

if this hypothesis is right, the French are right to prohibit Hepatitis vaccination.
in particular for MS and immune disease susceptible people (multi factoral issue incl. cell gates = mitochondrial health, EBV suppression by B-cells, ccsvi that inflammates the cartilage of dural sinus etc. etc)

this is really getting unbelievable; it all fits together in a plausible way...


and this thread also refers and provides very useful information and links:
http://www.thisisms.com/forum/general-d ... 24261.html

I am fascinated by the fact that at some point also the lungs get mentioned.
and that complete recovery from EBV seems possible.

I am sure healthy mitochondrial functioning plays a key role in keeping the EBV and immune complexes down.
a dysregulated endocrine system and such things as vaccination may aggravate the situation.
I can see a concept prevail here of dynamic viral load.

[Yodi]

The Charite University in Berlin experienced that 20 PwMS got much better by following the ketogenic diet

A ketogenic diet is the high fat and low carbohydrate diet. In this case, the fat content of the food is about 50 to 80 percent. The proportion of the sugar is dramatically reduced to 20 to 40 grams per day. This means a lot of fat, protein and fresh vegetables.

As we can notice food has a significant impact on MS. It might not stop it but it helps quite a lot.

The most important factor is to avoid carbohydrate-rich foods such as rice, pasta and potatoes and sweets completely.


links (in German)
http://www.dw.de/ketogene-di%C3%A4t-ein ... v-17379123
http://www.ndr.de/fernsehen/sendungen/v ... e8997.html

[Leonard]

Thanks Yodi.

It is not just neurologists in Berlin, neurologists around the world are waking up!
With a central role for mitochondrial health in progressive MS.

http://www.msif.org/includes/documents/ ... al.pdf?f=1
http://www.msif.org/global-ms-research/ ... ve-ms.aspx

quote: 2. Development of new and existing pre-clinical models for progressive disease based on
community consensus building
a. Identify experimental models of progressive disease targeting putative and novel pathogenic
mechanisms occurring in progressive forms of MS (e.g. mitochondrial dysfunction,...

With in my own case EBV causing the dysfunction, but for others the leaky gut could also contribute.

[Leonard]

There seems to be a direct link between EBV and the (inhibition of the) oligodendrocyte differentiation capacity and hence a direct path from EBV to MS:
http://www.ncbi.nlm.nih.gov/pubmed/23836485

Human endogenous retrovirus type W (HERV-W) envelope protein inhibits oligodendroglial precursor cell differentiation.

Our findings suggest that ENV-mediated induction of nitrosative stress via activation of TLR4 results in an overall reduction of the oligodendroglial differentiation capacity, thereby contributing to remyelination failure.

EBV and Herpes simplex are members of the W family of human endogenous retroviruses (HERV-W).

If this is true, I think the rest is secondary, the lesions, the distorted metabolic control. A retired immunologist recently explained to me that the "auto"immunity is nothing else than a cross-reaction of immune complexes with transgenic cells that contain residues of viruses that share common epitodes with, for example, EBV. Transgenic cells are inherited or acquired during times of low-immunity (e.g. in early foetal status). The general dysregulation of the metabolism then finds its cause in a distorted HPA axis, a weak adrenal – cortisol – gut axis (and fat related metabolism causing lesions http://www.ncbi.nlm.nih.gov/pubmed/24470599) and possibly an (EBV) distorted vagus nerve return path.

EBV was already with us millions of years ago when we were still apes hanging in the trees of Africa. But the immune system was capable of effectively suppressing the virus, but not eliminating it entirely. Remainders of the virus are in our cells (as work on the human genome has shown) and are carried over from one generation to the next.

A chronic EBV infection can develop if our immune system becomes insufficient, e.g. because B-cells mitochondria work insufficient. EBV infected bone marrow stem cells may be a factor. As the immunologist explained, EBV/Herpes does best in stem cells to multiply (e.g. bone marrow or oligodendrocyte precursor cells-OPCs). Our Western lifestyle and diet are suspect to weaken the immune system (stress, lack of vitamin D, sunlight, lack of good fat metabolism, lack of anti-oxidants and phytonutritients, "grainisation", vaccinations etc).

This article is interesting as it links a number of malignancies to chronic active EBV disease. I recognize some of these in my own family namely nasopharyngeal carcinoma and coronary artery aneurysm.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2776035/
I also recognise the symptoms on this photograph of the neck, in particular at the height of the disease activity when I was diagnosed with MS.
At the time, I remember a doctor suggested to use after-shave but clearly there was more to it...
http://en.wikipedia.org/wiki/Herpes_zoster

Now I do not believe in coincidence anymore. I do believe that I have a chronically active EBV and start take anti-viral medication.

[Anonymoose]

So your thinking is that if we reduce the presence of ebv our immune reaction to it will be decreased and therefore our "autoimmune" attack on transgenic cells will lessen? How does that work with adoptive immunotherapy in Pender's ms case study? It seems like it would take longer than two weeks (time lapsed before improvement noted) to reduce the immune reaction to ebv...especially since anti lmp1 and lmp2 cd8+ T cells were being administered for longer than two weeks. Maybe I've misunderstood the gist of your post.

My gut tells me the ebv infected B cells are erroneously releasing antibodies that attack our tissues and other things that interfere with remyelination. It's not a matter of transgenic targets...it's a matter of not clearing out the ebv infected cells as we should. That's all gut and little brain though. It all winds up at the same place though. Kill ebv and you are better off...maybe.

What's your anti-viral plan??

[Leonard]

So your thinking is that if we reduce the presence of ebv our immune reaction to it will be decreased and therefore our "autoimmune" attack on transgenic cells will lessen?

That is the idea and the hope....

How does that work with adoptive immunotherapy in Pender's ms case study?

If I understand correctly, the work of Pender for MS is part of a much bigger 'enterprise' to stop autoimmunity by manipulating T cells, arguably impaired T-cells that should work insufficiently against EBV. But I seem to remember from what I learned here before that there is also a B-cell issue, where the lack of mitochondrial functioning of B cells due to insufficient anti-oxidants would give room to EBV to get out of control...

It seems like it would take longer than two weeks (time lapsed before improvement noted) to reduce the immune reaction to ebv...especially since anti lmp1 and lmp2 cd8+ T cells were being administered for longer than two weeks. Maybe I've misunderstood the gist of your post.

I do not understand, please explain.

My gut tells me the ebv infected B cells are erroneously releasing antibodies that attack our tissues and other things that interfere with remyelination. It's not a matter of transgenic targets...it's a matter of not clearing out the ebv infected cells as we should. That's all gut and little brain though. It all winds up at the same place though. Kill ebv and you are better off...maybe.

I do not think that B cells erroneously release antibodies that attack our tissue, I think the process is normal and has been part of the human being, for long long time. But if B-cells/antibodies are insufficient to surpress the EBV/Herpes simplex/zoster infection, it becomes chronically active, immune complexes become chronically very high and cross-reaction (what we see as autoimmune reaction) will be very much elevated. Whether this causes the lesions is another matter because also the fat metabolism is involved here as the above Buffalo study shows... And whether this causes the remyelination failure is also a question. In fact, the EBV envelope protein may establish a direct channel to remyelination failure. The fat metabolism, the lesions, the auto immune reaction etc would then all become secondary phenomena..

What's your anti-viral plan??

1600 mg/day Zovirax for 2 weeks and a new blood test in 6 weeks on EBV/Herpes immune.

[Anonymoose]

Apologies for terrible formatting of response...posting from phone.

It seems like it would take longer than two weeks (time lapsed before improvement noted) to reduce the immune reaction to ebv...especially since anti lmp1 and lmp2 cd8+ T cells were being administered for longer than two weeks. Maybe I've misunderstood the gist of your post.

I do not understand, please explain.

That was just another gut thinking. Basically, I think it would take longer than two weeks to significantly reduce our immune reaction to ebv, especially in the CNS as antibodies are slow to clear there. The patient in Pender's study started experiencing improvements two weeks into the study. The improvements had to be placebo or related to something other than reduced immune reaction to ebv/transgenic cells.

My gut tells me the ebv infected B cells are erroneously releasing antibodies that attack our tissues and other things that interfere with remyelination. It's not a matter of transgenic targets...it's a matter of not clearing out the ebv infected cells as we should. That's all gut and little brain though. It all winds up at the same place though. Kill ebv and you are better off...maybe.

I do not think that B cells erroneously release antibodies that attack our tissue, I think the process is normal and has been part of the human being, for long long time. But if B-cells/antibodies are insufficient to surpress the EBV/Herpes simplex/zoster infection, it becomes chronically active, immune complexes become chronically very high and cross-reaction (what we see as autoimmune reaction) will be very much elevated. Whether this causes the lesions is another matter because also the fat metabolism is involved here as the above Buffalo study shows... And whether this causes the remyelination failure is also a question. In fact, the EBV envelope protein may establish a direct channel to remyelination failure. The fat metabolism, the lesions, the auto immune reaction etc would then all become secondary phenomena..

From what I understand, msers have elevated antibodies to ebv, even more so during relapse. I don't think general antibody failure is the problem. Maybe msers don't make the antibodies to the optimal target for ebv though. B cells that produce autoreactive antibodies for whatever reason are supposed to be cleared out...there is evidence that msers fail to clean up those bcells...a B cell tolerance defect. Pender believes it's the T cell reaction to ebv is lacking in ms. I wonder if that isn't set off by stress/trauma and maintained by something ebv infected cells release in greater quantities once they are allowed to spread or maybe it's our own natural protective immune suppressive response that causes the T cell failure.

What's your anti-viral plan??

1600 mg/day Zovirax for 2 weeks and a new blood test in 6 weeks on EBV/Herpes immune.

Good luck with that. I had a rough time of it on 1500mg valacyclovir. Hope it goes better for you!

[Leonard]

I do not know enough about T-cells, B-cells and other immunological aspects. But sometimes I wonder whether the real experts do know themselves. It occurs to me that even for them there is quite a bit of guess work while their frame of mind or conceptual approach may not necessarily be the right one either. Let me explain.

A lot of studies have lately been done on vitamin D supplementation. For sure, it will do something in the gut, for the immune system etc. Some of the thinking has passed here as well. But I am less confident that supplementation is good for myself. If I take it, the noise in my head increases substantially; and an old weakness surfaces (inflammation of the shoulder). Few years ago, when the MS disease activity was high, I noted my vitamin D had dropped after the Summer despite all the sunshine… I think the vitamin D regulatory system of the body is more advanced than we think.

Let me complicate things a bit more at first. If we distill cod liver oil in its constituent elements, we find a combination of vitamin D, vitamin A and Omega 3 fats. And we know the cod liver oil that nature provides is good for us. My question is then: what do we miss if we take just vitamin D supplements? What useful synergies have not been understood?

By the same token, our lesions presumably have something to do with an attack of immune complexes on transgenic cells. But as the Buffalo study shows, and as Swank has shown, it is also related in some way to the fat metabolism. The constituent elements of MS then are on teh cross-roads of disciplines as immunology, virology, genetics, and the fat metabolism. But then, my question is: What do we miss here? What synergetic effects have not been understood e.g. because of combined effect of fat metabolism and immune complexes?

I consider my MS to be related to some malignancies seen in my own family (nasopharyngeal carcinoma, coronary artery aneurysm, mitochondrial energy failure) and hence to a chronically active EBV. And then, perhaps we need to cut across our disease in a different way altogether. Putting the HERV-W, mitochondrial health detox anti-oxidants, healthy membranes phosphor center stage.

As an immunologist knows, the HERV-W can have many faces. This is where it becomes even more interesting for MS. In fact, I think this could well explain RR with the VZV (varicella-zoster-virus) as early stage inflammatory (this is what immunologist knows)blocking nuclear receptors (this is my explanation) as well as progressive MS with the EBV (Epstein-Barr virus) as later stage onco virus damaging or inhibiting dendrocytes. whow...

[Leonard]

I am now taking Zovirax. It is one of the most commonly used anti-viral drugs. The active ingredient is aciclovir or acyclovir. http://en.wikipedia.org/wiki/Aciclovir

http://www.drmyhill.co.uk/wiki/Valacycl ... e_syndrome
Chronic Epstein-Barr virus and other human herpes viruses may be a cause of long term symptoms in chronic fatigue syndrome. Treatment with anti-virals is effective in restoring sufferers to health. The article points to this article:
Lerner, A. Martin et al (2010). "An update on the management of glandular fever (infectious mononucleosis) and its sequelae caused by Epstein–Barr virus (HHV-4): new and emerging treatment strategies." Virus adaptation and treatment.
Conclusion: Nonpermissive EBV infection is causal in a significant proportion of CFS cases.
EBV CFS is safely and effectively treated with long-term valacyclovir.
The figures in the paper point to recovery starting after a few months with full recovery after a year.

Now, what is going on here?
Are mitochondrial energy failure, Chronic Fatigue Syndrome, my version of EBV inspired MS, are they all one and the same disease caused by the same viral infection?
And is treatment by (val)acyclovir effective including for MS?

I know all this information is compiled from fragments that resulted from Google searches.
Yet, I think it is not entirely void, there must be something into it.
My hope is reinforced at this point that it will show its effects sooner or later..

@ Anonymoose: a bit contrary to your experience, I take Zovirax now for one week and have no side effects whatsoever. A Google search also reveals that it is very well tolerated.

[Kronk]

The Charite University in Berlin experienced that 20 PwMS got much better by following the ketogenic diet

A ketogenic diet is the high fat and low carbohydrate diet. In this case, the fat content of the food is about 50 to 80 percent. The proportion of the sugar is dramatically reduced to 20 to 40 grams per day. This means a lot of fat, protein and fresh vegetables.

Very interesting… I think it’s unusual that many diets with conflicting methodologies show some efficacy. Swank and OMS for example preach the opposite of the KetoGenic and push the reduction of fats and the anecdotal and clinical evidence is hard to dismiss. Perhaps it’s less the quantity of fats in the diet and more the ratios of fats…

For example Swank promotes an approx. 4:1 ratio of polyunsaturated (PUFA) and unsaturated to saturated fats. OMS says to eliminate all saturated fat if possible. Anyone doing the Ketogenic would need to consume a ton of PUFA unless they want a huge spike in bad cholesterol from animal fats. Due to multiple research studies showing that pwMS have elevated levels of saturated fat and reduced PUFA in plasma I adopted the Swank diet. With the exception that I do not limit my PUFA. This was for 3 reasons…
1. I got uncomfortably skinny losing 30+lbs from an already lean frame
2. My energy levels were unbearably low
3. I just don’t think the reduction of PUFA was related to the efficacy of his diet.

Lipid peroxidation has also proven to be elevated in pwMS and many other neurological diseases. Lipid peroxidation refers to the oxidative degradation of lipids (fats). It is the process in which free radicals "steal" electrons from the lipids in cell membranes, resulting in cell damage. You can draw various conclusions as to why this is happening in pwMS but it may be due to the fact we have insufficient amounts of PUFA in the body, or an issue with the availability of them. Also add to this the fact that pwMS have reduced PUFA in cell membranes, which would increase the damage done to individual cells.

There are other issues relating to the fact PwMS have higher levels of saturated fatty acids in plasma. Through 5-lipoxygenase activation (5-LOX, a protein activator of leukocytes) Very Long Chain Fatty Acid accumulation causes a lipotoxic response (demyelination). What is interesting is that monoeonics (un-saturated fatty acids) were shown to block the expression of 5-LOX and prevent the demyelination. This again points to the imbalance of saturated to unsaturated fatty acids in neurological disorders.

So many diets, so many positive results, but NO data linking the mechanisms of action...
My modified version of Swank, excersize program, meds and supplements seem to have tamed my beast. Hopefully its for the long term...

Study showing high lysolecithins in pwMS (derived from saturated fat)
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC494425/

Study showing fatty acid ratio in MS
http://www.pnas.org/content/86/12/4720.full.pdf

MS brains have reduced polyunsaturated fatty acids.
http://link.springer.com/article/10.100 ... 801#page-1

LPx in central nervous system may be a feature of MS.
http://link.springer.com/article/10.100 ... 606#page-1

PUFA anti-inflammatory
http://ajcn.nutrition.org/content/83/6/S1505.full

[Anonymoose]

I am now taking Zovirax. It is one of the most commonly used anti-viral drugs. The active ingredient is aciclovir or acyclovir. http://en.wikipedia.org/wiki/Aciclovir

http://www.drmyhill.co.uk/wiki/Valacycl ... e_syndrome
Chronic Epstein-Barr virus and other human herpes viruses may be a cause of long term symptoms in chronic fatigue syndrome. Treatment with anti-virals is effective in restoring sufferers to health. The article points to this article:
Lerner, A. Martin et al (2010). "An update on the management of glandular fever (infectious mononucleosis) and its sequelae caused by Epstein–Barr virus (HHV-4): new and emerging treatment strategies." Virus adaptation and treatment.
Conclusion: Nonpermissive EBV infection is causal in a significant proportion of CFS cases.
EBV CFS is safely and effectively treated with long-term valacyclovir.
The figures in the paper point to recovery starting after a few months with full recovery after a year.

Now, what is going on here?
Are mitochondrial energy failure, Chronic Fatigue Syndrome, my version of EBV inspired MS, are they all one and the same disease caused by the same viral infection?
And is treatment by (val)acyclovir effective including for MS?

I know all this information is compiled from fragments that resulted from Google searches.
Yet, I think it is not entirely void, there must be something into it.
My hope is reinforced at this point that it will show its effects sooner or later..

@ Anonymoose: a bit contrary to your experience, I take Zovirax now for one week and have no side effects whatsoever. A Google search also reveals that it is very well tolerated.

Yep. There have been studies for acyclovir for ms...and I guess it is usually well tolerated. I tolerate 500mg valtrex quite well since rituxan...haven't tried 1500mg yet. Here's a 2400mg/day study...
http://www.ncbi.nlm.nih.gov/m/pubmed/8936350/
You'll note 62 exacerbations in 30 guinea pigs over two years. I relapsed on 1500mg/day valtrex at an atypical time of the year for me to relapse and that is what I refer to as a rough time. Oddly, the relapse pretty much stopped and I started to recover when I discontinued the valtrex. The whole thing only lasted 2 weeks compared to my usual 8 weeks. I guess if you relapse, you should push through and carry on with the valtrex. Since acyclovir is an IDO inhibitor and IDO inhibitors have been proven to exacerbate eae, you should probably expect a relapse if you are still RR. Then again, scott1 took 1000mg/day with avonex and from what I understand never relapsed.

[Leonard]

I think the double peak in the graph of the age of onset of MS is much more telling than one might think at first sight. I think underlying the double peak are two fundamentally different mechanisms: the first is related to for instance VZV (varicella-zoster-virus) blocking nuclear receptors; the second is related to a chronically active (activated) EBV (Epstein-Barr-virus) inhibiting OPC differentiation. The first is causing the ion pump to run down, inflammation to signal the immune system that there is something wrong, the virus is removed and we see remittance (RR). The second causes slow degradation of the (number of) oligodendrocytes and of nervous cells. The first is a fast process, almost instantaneous, almost overnight; the second is a slow process that takes years. The second is not dependent on previous RR disease activity - perhaps we should say is independent of, reinforcing the hypothesis of a different mechanism - where its start has some relationship with age.

The common thinking among neurologists (arguably they have no direct experience with the symptoms themselves or a life-long trail as a patient does) is that the RR causes some oligodendrocytes to fail which are then replenished by new cells from OPCs. And when transitioning to progressive MS, gradually a bigger number of oligodendrocytes fail that are then insufficiently replenished. The mechanism behind progressive would then just be a bit more of RR. But I think in that case the graph of age of onset would not show a double peak, it would just reach a peak and then taper off slowly. You have to think this over a few times, to get your head around it. I think it is one of the biggest dogma's that the neurologists still need to relinquish; to see and admit that there are different mechanisms that cause MS in its various stages.

@ Anonymoose: But in that case, that is to say that there are two very different mechanisms of action underlying MS, the treatment of RR and progressive could also have to be very different. If you take Zovirax in RR, you may well experience some short-term problems for instance because VZV gets on to your receptors (assuming this is the mechanism). But then, progressive would be very different. If it is true that MS at that stage is EBV inspired, and that it is the EBV envelop protein that inhibits differentiation of the OPC's, you might well expect a completely different response to Zovirax from RR. The experiences with the EAE model would seem of little value there. And the study you quote would also seems of little value for these progressive patients. For them, I think the effects of Zovirax can only be measured on the long-term, from many months to years.

[vesta]

Hello Leonard: It's interesting that you have such a high level of EBV antigens. Are you considering the rétrovirus issue? ("See Re: MSRV Rétrovirus, phase 2") When I read that thread I inserted this in my main paper.

"Ah, but I can't ignore the impression that after this past winter's flu. I've been dragging along, unable to fully recover. This has happened before where I feel like something is "eating" at me. Here we come to another angle currently being studied in France, England and Switzerland which can't be overlooked - the role of the Epstein-Barr Virus - EBV (Mononucleosis which I had at the age of 9 being an example.) My rough understanding of these studies is that remnants of the Epstein Barr Virus (among others) imbedded themselves in human genes over millions of years of evolution. If an individual with this genetic inheritance falls ill with an Epstein Barre virus illness, the immune system reaction to the virus ends up attacking the inherited DNA - hence the "self". Unlike current MS drugs designed to modulate or suppress the immune system, the proposed medication is designed to shut down the MS associated retrovirus and therefore the auto-immune demyelinating cascade which occurs when the latent Epstein-Barr virus periodically re-activates.

The recent flu left me weakened. Has the latent mononucleosis virus revived and is my immune system reacting against an inherited Human Endogenous Retrovirus (HERV) imbedded in the genes?

Conclusion: I must deal with the blood reflux on a daily basis. And not get sick."

End of quote. That may not be the best conclusion. I'll be interested to know the outcome of your treatment. I admit I haven't read all the posts since you announced your current antiviral treatment. Best

[leonardo]

IMHO CFS is 1st stage of ms so I'm posting this study here:

Deficient EBV-Specific B- and T-Cell Response in Patients with Chronic Fatigue Syndrome
http://www.plosone.org/article/info%3Ad ... ne.0085387

study findings:
- EBV-specific memory B cells are low or absent in most CFS patients
- Evidence of enhanced latent EBV replication in CFS patients

looks like ebv itself is not an issue, the problem is that the body loses the ablility to control ebv and so the replication...

do you think this study is also applicable to ms?

[Anonymoose]

Hi Leonard & all,
Didn't mean to rudely abandon the thread! I just find myself unable to apply further thought to the ebv/ms issue. As of now, there is no proof that ebv is running some of the ms shows. We don't know all that it does or how it works. Seems a fruitless labor for a lay person to try to figure out how it makes things go awry in some. The only thing that can be done is experimentation. So, I'm experimenting. It will be decades before they tie down all the ways in which ebv effects us. I'll just be happy with improvements/stability if any is to be had from an ebv killing crusade.

Hope you are doing well on the acyclovir.

Leonardo,
I don't think you can apply the data from csf studies to ms. There are plenty of ms/ebv studies out there though. Pender thinks it's a low cd8+ T cell reaction to ebv that contributes to ms. I believe msers have elevated antibodies to ebv too...that seems to argue against insufficient ebv specific B cells in msers. But I really haven't a clue!