Theoretical Immunology

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Leonard
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Re: A new concept and treatment options for MS

Post by Leonard »

We have seen that the oxidative stress cycle originates from a herpes viral infection.

As the following article suggests, it may now well be that herpes viral spreading is facilitated by oxidative stress.
That is bad because it would be a further stimulous for the vicious cycle, a sort of self-perpetuating mechanism that is launched by an MS attack, iNOS production and cellular expression.

The good thing is that, while herpes viruses are favoured by oxidative conditions, studies also suggest that a disruption of these conditions can reduce herpes infection. Some antioxidants may be more efficient than others in reducing infection. In fact, if you look at Fig.3 in the article, the reduction can be quite substantial.


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5829443/

Quote: The results from our first MA support our first hypothesis that herpes virus infection caused increased OS across diverse vertebrate species, but this effect was contingent on the tissue and biomarker of OS. Our second MA supports our second hypothesis that an increased intake of antioxidants reduced the virus load, indicating that the viral replication may be favored by a status of OS. The positive effects of antioxidant administration were dependent on the concentration and the kind of antioxidant.

= = =

post script: The matter is not straight forward. As the following article suggests, oxidative stress may activate genes and as such it may act as a brake for T cells and keep them in check. https://news.ki.se/unexpected-effect-of ... 1577123303
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Re: A new concept and treatment options for MS

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On the Internet we find a mountain of medical publications, often in the open literature. Most of these publications consider the problem "in their own domain" resulting in an incomplete picture. But if we bring it all together, we can see a huge breakthrough on the horizon built on a series of interdependent innovations.

The battlefield that emerges is one of the power of patient fora on the Internet vs the power of the medical system. The latter sucks innovation and acts as a barrier to change. The question is now: How can the former help us to force change?
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Re: A new concept and treatment options for MS

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"The battlefield that emerges is one of the power of patient fora on the Internet vs the power of the medical system. The latter sucks innovation and acts as a barrier to change."

You are pretty much correct.


"The question is now: How can the former help us to force change?"

Force change? Doubtful, there is no simple solution that can correct this but to me there is a solution - to take matters into our own hands. There is a saying "If it is meant to be, it is up to me." I have always lived by this philosophy. And have followed this simple principle since my diagnosis as I quickly realized that modern medicine could not really help me. Like many others have done and done successfully, it is possible to treat yourself successfully and that is what I have been doing. I have done and continue to do research on a daily basis - there is a lot of helpful info out there and always new ideas being presented, all you have to do is look. And there seems to be new ideas popping up regularly. I often make changes to my treatment on a weekly basis. Waiting for the right answers and solutions from the medical system over the short to medium term is really not an option that will help anyone now or in the near future.
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Re: A new concept and treatment options for MS

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ElliotB wrote: Mon Feb 11, 2019 1:03 am "The battlefield that emerges is one of the power of patient fora on the Internet vs the power of the medical system. The latter sucks innovation and acts as a barrier to change."

You are pretty much correct.


"The question is now: How can the former help us to force change?"

Force change? Doubtful, there is no simple solution that can correct this but to me there is a solution - to take matters into our own hands. There is a saying "If it is meant to be, it is up to me." I have always lived by this philosophy. And have followed this simple principle since my diagnosis as I quickly realized that modern medicine could not really help me. Like many others have done and done successfully, it is possible to treat yourself successfully and that is what I have been doing. I have done and continue to do research on a daily basis - there is a lot of helpful info out there and always new ideas being presented, all you have to do is look. And there seems to be new ideas popping up regularly. I often make changes to my treatment on a weekly basis. Waiting for the right answers and solutions from the medical system over the short to medium term is really not an option that will help anyone now or in the near future.
Greetings:

I fully agree with ElliotB. It's up to us to take care of ourselves.

Best, Vesta
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Re: A new concept for MS and other autoimmune diseases

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Elliot, Vesta, thank you. I agree with you that we must take care of ourselves. That is what I try to do as well.

But besides what we do in our own private sphere, public intervention and funding would seem logical because there is not a patentable molecule involved here, the underlying thinking (see essay below) is an orphan hypothesis.

And public intervention is much needed as well as the medical system is completely locked up; the inertia of the status quo is too great, every change initiative seems impeded.

We need to open up the medical system and involve thousands of interested parties discovering the alternatives and connecting the interdependent innovations and new insights.

The essay in the next posting sketches the bigger picture on autoimmunity and our society and stresses the need for government action. Governments on both sides of the ocean should now take their responsibility.
Last edited by Leonard on Sat Jun 08, 2019 2:47 am, edited 3 times in total.
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Autoimmunity and our society

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Autoimmunity and our society

[later amendments and additions in italics]

Our cells have very small deviations, called Single Nucleotide Polymorphisms (SNPs) which have always been considered to be irrelevant. But they are not, they are very important as they are gatekeepers that signal whether a cell is infected by a (double stranded) herpes virus. They are thought to be part of the innate immune system as a defense against double stranded viruses. SNPs are somewhat genetically determined, by inheritance. That is why for instance Rheuma Arthritis or Alzheimer's is seen more in some families than in others. If the cell does not trigger internal cytokine/interferon mechanisms (of the RNA interference complex) to keep the virus down, the cell will get predestined. Herpes SNPs are mainly located in the X-chromosome which explains the gender bias in autoimmunity and indeed in diseases as Alzheimer's.

The systemic immune system gets also loaded with herpes but normally does not recognise the infected cells; there is viral tolerance. Biological evolution of many hundreds of Millions of years lies at the basis of our herpes immunity (core components of the miRNA pathway mechanism are even conserved between the two kingdoms of plants and animals); but the immune system never got rid of herpes completely, and all people have it. The problem comes when the gut microbiome, which co-evolved with the genome for more than 2 Billion years, does no longer control the epigenetics - miRNA regulatory system of the cells and cells come to expression.

If cells are no longer silenced, B cells cross react with endothelial cells and then a biological mechanism starts to kill the pathogen. In some cases this may be preceded by T cells causing physiological trauma. The mechanism is called autoimmunity. And other biochemical processes 'unfold', in particular oxidative stress. This causes diseases as Alzheimer's, Rheuma Arthritis, Asthma, Lupus, Chronic Fatigue Syndrome, etc. Multiple Sclerosis is a special case in the sense that, more than SNPs, vascular narrowings compromise the blood brain barrier and allow the viral loading, but the unfolding is the same.

24 Million people in the US have an autoimmune diagnosis, but another 50 million do not feel well and have autoantibodies but do not yet have enough antibodies to make a diagnosis. So, that means about 75 million have autoimmune problems. Even more disturbing, more and more children are being diagnosed with an autoimmune problem as children. For Europe, the statistics won’t be very different. Despite the increase in longevity which may be attributed to new medical techniques, drugs and technology, we are as a society progressively less well.

Why is this happening to us? What has given rise to the single largest epidemic of chronic disease in human history? Have our genes gone bad or have we adopted a lifestyle that could explain the current scourge of autoimmune diseases? Since the weight of genetic changes to our DNA is insignificant in a short period of a few generations, we will need to search the causes at the environmental level. Our modern Western lifestyle over the last 50 years (see footnote) has broken with the evolutionary path of many millions of years and led us down a very dangerous path.

The situation has to change. Underlying is a real paradigm change, like Kepler's theory in the 17th century. As the inertia of the status quo is so great, I think only the US government together with the 27/28 European governments in the EU can initiate change. The scourge of autoimmune diseases which will soon affect over 25 percent of our societies and is growing fast merits an urgent effort at scale to clarify and address the underlying causes.



_________________________
Footnote: environmental changes:
- indoor life and the low cholesterol con; diet: e.g. shifting fat balance, lack of (phyto)nutritients; vaccinations with virus; use of antibiotics (= clusterbombs for our microbiome); we lost famine/periods of fasting (=reset microbiome) and traditions as fish on friday (=shift back fat balance); we wash away/destroy the natural microbiome of ourselves/our food; Caesarean section and infant formula feeding; ...)

- then, there are the environmentally induced responses of the microbiome - epigenetic - RNA interference complex (hairpins from retrovirus carried by herpes?) that result in epigenetic marks. These are part of an indirect more short-cycle evolutionary or adaptation mechanism and may be heritable and transmitted from one generation to the next.
- add to this that herpes proliferation is promoted by oxidative stress conditions and thus creates a vicious cycle. Saturated fats help herpes spreading.
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Re: A new concept for MS and other autoimmune diseases

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The iNOS Activity During an Immune Response Controls the CNS Pathology in Experimental Autoimmune Encephalomyelitis

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6458273/
from viewtopic.php?f=1&t=30982

My view:
iNOS is the result of a physiological trauma induced by T cells (inflammation).
Highly localised oxidative stress results from iNO reacting with superoxide from EBV B cells that find common epitopes (progression).

- - - - - - -

Epstein-Barr Virus and miRNAs: Partners in Crime in the Pathogenesis of Multiple Sclerosis?

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6456696/
from viewtopic.php?f=1&t=30969

My view:
The herpes virus causes MS, EBV is a herpes strain.

The recognition of the virus at cellular level is done by SNPs.
And likely via SNPs the miRNA is involved in B cell transformation.

The SNPs function within the miRNA and within miRNA targets.
As such, SNPs modulate miRNA or are associated with miRNA regulation.

The polymorphisms are the result of hundreds of millions of years of evolution.
Fish have some of the same polymorphisms as human beings, indicating they date back from the common root from a long time ago.
And a significant part of our cells have miRNA.
Cells protected by the blood brain barrier had no need to develop SNPs, so in an evolutionary sense, these cells e.g. like myeline will be less protected.

I found this information very helpful (just google a bit on it and Google will bring the most interesting publications forward):

https://en.wikipedia.org/wiki/MicroRNA
https://en.wikipedia.org/wiki/Small_interfering_RNA and how human cells are invaded

articles on RNA and evolution

articles on the classification of herpes as a retro virus and on retrovirus insertion into herpesvirus (yes!!, is herpes only the carrier?? or even, in some cases, could the hepatitis virus be the carrier? or could the yellow fever retro virus cause the disease?)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC48371/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6456696/

tutorial lessons on youtube like the series on RNA interference and siRNA / shRNA / miRNA



articles on SNPs within or flanking microRNA

and articles on the interaction of the microbiome with microRNA and SNPs


Again the publications fully confirm the above picture on autoimmunity
Last edited by Leonard on Sat Sep 07, 2019 8:45 am, edited 18 times in total.
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We need a paradigm change

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The medical sector does not know what is or what causes MS. But it's even worse than that. In fact, they don't know what is autoimmunity, what causes autoimmune diseases. But I am sure some day the health paradigm will change.

If we look back at the old (= our current) health paradigm in say 2030, we will look at it in much the same way that people looked at our solar system before Kepler when the movement of each planet was described by 40 or so superimposed circles around the Earth. In Kepler’s paradigm, this was greatly simplified by putting the Sun in the centre and an ellipse to describe each planet’s orbit. Likewise, in stead of all the multiple pathologies and (overlapping) co-morbidities we have today, we will look at autoimmune diseases in a much simplified manner i.e. as a herpes virally induced disease in a variety of permissible cells that come to expression because of a gut insufficiency. The full picture is given in the above posting on autoimmunity and our society: viewtopic.php?f=1&t=15188&start=885#p257234

For most of us, MS is caused by vascular narrowings in the neck (CCSVI) which breaches the blood brain barrier and then allows for the viral entry. For other autoimmune diseases, cells may permit viral infection because they lack the right SNPs.

This paradigm change will turn the medical system upside down. Let us just hope that soon, very soon, this new view on chronic autoimmune diseases will gain traction and an urgent effort will be launched to clarify and address the underlying causes.
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Autoimmunity and our society

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The mystery of autoimmune diseases revealed

Taking control of autoimmunity: a scourge of our modern age



Autoimmune diseases—such as multiple sclerosis (MS), lupus, Crohn’s disease, type 1 diabetes, and rheumatoid arthritis—cause the body to destroy itself. Recent studies suggest that the mechanisms of other chronic diseases such as Alzheimer’s and Parkinson’s are also autoimmune. The prevailing belief is that in all these diseases, by different pathways, the immune system is triggered to mistakenly attack healthy cells.

The growth of autoimmune diseases is alarming. Some increasingly strong evidence would suggest that the trend is linked to some characteristics of our modern lifestyle, notably the countless environmental triggers that we are exposed to every day. That is until today. The following essay tries to shed additional light on the still obscure field. By connecting interdependent innovations and new insights into a bigger picture, we hope to make clearer what autoimmunity is and why now is the time for new levels of action.


The viral culprit

Our cells have very small deviations from the equilibrium, called Single Nucleotide Polymorphisms (SNPs). The function of SNPs has not been clarified, and has largely been dismissed as unimportant. But on the contrary, it is now clear that SNPs are very important as the gatekeepers that signal whether a cell is infected by a herpes virus. They are thought to be part of the innate immune system and the body’s evolved defence against double-stranded viruses. SNPs are somewhat genetically determined. That is why for instance Rheuma Arthritis or Alzheimer's is seen more in some families than in others. If the cell does not trigger internal cytokine/interferon mechanisms (of the RNA interference complex) to keep the virus down, the cell will get predestined. Herpes SNPs are mainly located in the X-chromosome which explains the gender bias in autoimmunity and indeed in diseases as Alzheimer's.

The systemic immune system also gets loaded with herpes but normally does not recognise the infected cells; there is a situation of viral tolerance. Biological evolution of many hundreds of millions of years, perhaps even billions of years, lies at the basis of our herpes immunity. This may be deduced from the fact that core components of the miRNA pathway mechanism are conserved between the two kingdoms of plants and animals. But the immune system never got rid of herpes completely, and all people have it.


The autoimmunity problem

The autoimmunity problem comes when the gut microbiome, which co-evolved with the genome for more than 2 billion years, stops functioning as a control of the epigenetics of certain cells and cells come to expression. If endothelial cells are no longer silenced because of gut malfunctioning, B cells cross-react with endothelial cells and a biological mechanism starts to kill the pathogen i.e the virus, in particular shedding superoxide (Ref 1). The mechanism is called autoimmunity. This may be preceded by (specialised) T cells causing physiological trauma such as MS lesions and inducible nitric oxide production (Ref 2). Here, the number of mitochondria per cell is important too. As the ATP pool of the cell declines and the ADP rises, the intra-cellular anti-viral activity weakens as does its ability to control inflammation (Ref 3).

As a result of this biological cross-reaction other biochemical processes 'unfold', in particular oxidative stress. This may give rise to all sorts of autoimmune diseases and comorbidities depending on where in the body the highly localised oxidative stress develops as a result of prior viral anchoring. Multiple sclerosis is a special case in the sense that, more than SNPs, vascular narrowings compromise the blood brain barrier and allow the viral loading, but the unfolding is the same (Ref 4). Parkinson’s is believed to be caused by the death of dopamine producing cells due to prior viral leakage into these brain cells.


Autoimmunity is becoming a real scourge in our society

24 Million people in the US have an autoimmune diagnosis, but another 50 million do not feel well and have autoantibodies but do not yet have enough antibodies to make a diagnosis. So, that means about 75 million have autoimmune problems. Even more disturbing, more and more children are being diagnosed with an autoimmune problem before reaching adulthood. For Europe, the statistics won’t be very different. Despite the increase in longevity which may be attributed to new medical techniques, drugs and technology, we are as a society progressively less well.

Why is this happening to us? What has given rise to the single largest epidemic of chronic disease in human history? Have our genes gone bad or have we adopted a lifestyle that could explain the current scourge of autoimmune diseases?

Since the weight of genetic changes to our DNA is insignificant in a short period of a few generations (changes are measured over millions of years), we need to seek the causes at the environmental level. Our modern Western lifestyle over the last 50 years has led us down a very dangerous path.


Triggers for autoimmunity and their inheritance

There is a large number of environmental changes that may contribute to the current increase in the prevalence of autoimmunity, either because they predestine the cells or because they directly trigger disease. Among them: our indoor life and the low cholesterol hype leading to a chronically low Vitamine D weaken the internal structure of our cells with a lower mitochondria count in cells of newborn life and young adults and a lower resistance to developing autoimmune disease; the fat balance is shifting towards saturated fats making microglia function less effective following CNS viral infection and depleting other immune cells; we lost good traditions as fish on Friday which help to shift back the fat balance; our food lacks phytonutritients and natural anti-oxidant components inter alia because of hydroponic plant growth and soil depletion; antibiotics are cluster bombs for our microbiome, impaired gut microbial signaling negatively influences microglia function that normally should prevent viral induced neurological disease; hardened grains further deplete IgA which may already be scarce - celiac disease is not a black and white issue - leading to gut insufficiency; in our modern society with an oversupply of food we lost famine and periods of fasting which are important because they reset the microbiome, starvation leads to new mitochondrial dynamics that enhances the anti-viral properties of the cell; we wash away/destroy the natural microbiome of ourselves/our food; infant formula feeding weakens the microbiome until many year after childhood; vaccine adjuvant activity may help viral spreading while vaccinations with viruses (e.g. Hepatitis B) may bring retroviral components into cells that trigger the RNA interference complex thereby inhibiting silencing genes and causing new cellular expression.

On top of this, and that makes it even more worrying, there are the environmentally induced responses of the microbiome - epigenetic - RNA interference complex that result in epigenetic marks. These marks may lead to new gene expression and are part of an indirect more short-cycle evolutionary or adaptation mechanism and may be heritable and transmitted from one generation to the next.

We may add to this that herpes proliferation is promoted by oxidative stress conditions and thus creates a vicious cycle. Saturated fats help herpes viral spreading.


The need for a paradigm change

I am convinced that if we look back at the old (= our current) health paradigm in say 2030, we will look at it in much the same way that people looked at our solar system before Kepler when the movement of each planet was described by 40 or so superimposed circles around the Earth. In Kepler’s paradigm, this was greatly simplified by putting the Sun in the centre and an ellipse to describe each planet’s orbit. Likewise, instead of all the multiple pathologies and (overlapping) co-morbidities we have today, we will look at autoimmune diseases in a much simplified manner i.e. as a herpes virally induced disease in a variety of permissible cells that come to expression because of gut microbiome insufficiency.

But change won't come easy. Today, we are faced with a health system that is completely locked up. The inertia of the status quo is so great that every change initiative seems impeded. Public intervention at scale is required to open up the system and involve thousands of interested parties discovering the alternatives and connecting interdependent innovations and new insights. Because there is not a patentable molecule involved - this is an orphan hypothesis - public intervention and funding would seem logical.

I think government has an important role to play here. It is the task of government, any government, to provide security for its citizens. And that goes way beyond a military security or a cyber security. Hence, I believe that governments from around the world should initiate new medical health initiatives. The scourge of autoimmune diseases which will soon affect over 25 percent of our societies and is growing fast merits an urgent effort at scale to clarify and address the underlying causes.


The author is an MS patient who made this analysis against the background of his own experiences and with the help of social forums and the vast amount of medical literature on the Internet as well as some professional advice.
Hundreds of references from the medical literature backing this thesis may be found on this thread.

Refs:
1. https://www.clinicaleducation.org/resou ... -a-review/
2. https://elifesciences.org/articles/47117
3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5174094/
4. viewtopic.php?f=1&t=15188&start=825#p251748
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Re: A new concept for MS and other autoimmune diseases

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Petr75 wrote: Sun Sep 22, 2019 2:38 am 2019 Jul 16
Department of Pathology, Division of Microbiology and Immunology, University of Utah School of Medicine, Salt Lake City
The microbiota protects from viral-induced neurologic damage through microglia-intrinsic TLR signaling
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6634972/

Abstract

Symbiotic microbes impact the function and development of the central nervous system (CNS); however, little is known about the contribution of the microbiota during viral-induced neurologic damage. We identify that commensals aid in host defense following infection with a neurotropic virus through enhancing microglia function. Germfree mice or animals that receive antibiotics are unable to control viral replication within the brain leading to increased paralysis. Microglia derived from germfree or antibiotic-treated animals cannot stimulate viral-specific immunity and microglia depletion leads to worsened demyelination. Oral administration of toll-like receptor (TLR) ligands to virally infected germfree mice limits neurologic damage. Homeostatic activation of microglia is dependent on intrinsic signaling through TLR4, as disruption of TLR4 within microglia, but not the entire CNS (excluding microglia), leads to increased viral-induced clinical disease. This work demonstrates that gut immune-stimulatory products can influence microglia function to prevent CNS damage following viral infection.
The link did not work but I found the full article on viral-induced disease here: https://elifesciences.org/articles/47117

Although the article does not mention specifically the herpes virus, it does make reference to this study that links MS to herpes. https://www.ncbi.nlm.nih.gov/pubmed/22583435
Possibly, as we have seen, there may be other viruses such as Hepatitis B that trigger disease or that carry a smaller retro virus that triggers disease.
And from other references mentioned in the Introduction, we could infer that multiple viruses have been associated with neurological disease or have been implicated (Itzhaki et al., 2016; Kakalacheva et al., 2011; Stoessl, 1999; Tesoriero et al., 2016; Virtanen and Jacobson, 2012).

The article further seems to confirm Swank's low saturated fat hypothesis i.e that short chain fatty acids are able to influence microglia and thus the protection to viral-induced neurological disease.
The article also suggests that reductions in microbial stimulation through increased antibiotic use and sanitation contribute to the significant increase in autoimmunity and neurological disorders.

The article may be interesting for the neurologists because it connects the current work on the microbiome with many of the facets, language and jargon they are best known with, from within their own domain. It refers in particular to the very mechanisms that underly (the onset of) the inflammatory phase, see also Step 3 of the updated skeleton of MS on the specialised T cells general-discussion-f1/topic15188-825.html#p251748

But at the same time, the article fully confirms the bigger picture that emerges here on this thread, see the above essay on the mystery of autoimmune disease revealed. viewtopic.php?f=1&t=15188&start=885#p258372
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Re: A new concept for MS and other autoimmune diseases

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Besides the medical technical aspects, we have encountered here many times the systemic aspects of the problem.

As regards the latter, we may feel encouraged by this article where we learn that ever more prominent doctors speak out against the medical establishment and that it is starting to look like systems are no longer able to contain or censor inner dissent: https://www.collective-evolution.com/20 ... d-doctors/

This is not far from the very cynical and sceptical remarks that I recently heard from MS professionals about the latest ECTRIMS 2019 meeting and the usefulness or not of these big jamborees and the material presented there.
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Re: A new concept for MS and other autoimmune diseases

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From the other thread on Why Don't We Have a Vaccine Against Autoimmune Diseases?
Petr75 wrote: Fri Sep 27, 2019 10:07 pm 2019
Roseman University College of Medicine, Las Vegas
Why Don't We Have a Vaccine Against Autoimmune Diseases? - A Review.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6640150/

Abstract
This review examines some of the reasons why we don't have a vaccine against autoimmune diseases and highlights the progress that has been made. Many autoimmune diseases, such as rheumatoid arthritis (RA), multiple sclerosis (MS) and type 1 diabetes (T1D), are driven by autoimmune T cell responses. Unlike vaccines for most infectious diseases, which elicit antibody responses, are intended for immuno-naive individuals and considered preventative, a vaccine for an autoimmune disease must be therapeutic and resolve or control the on-going autoimmune response and condition in the diseased host. Despite these differences, many of the same considerations for infectious disease vaccines must also be addressed to develop a therapeutic vaccine for autoimmune diseases. The disease initiator/triggers, antigens and autoantigens, nature of the immunopathogenic and protective/therapeutic immune response will be compared for infectious and autoimmune diseases as will approaches for developing vaccines including formulations, animal models and indicators of success. The rationale for a therapeutic vaccine for RA will be discussed in greater detail with a relatively limited discussion of T1D, MS and other autoimmune diseases.


https://pdfs.semanticscholar.org/0e4f/f ... e44f6f.pdf

Vaccination and Autoimmunity—‘Vaccinosis’: A Dangerous Liaison?

quote
The question of a connection between vaccination and autoimmune illness(or phenomena) is surrounded by controversy. A heated debate is going on regarding the causality between vaccines, such as measles and anti-hepatits B virus (HBV), and multiple sclerosis (MS). Brain antibodies as well as clinical symptoms have been found in patients vaccinated against those diseases. Other autoimmune illnesses have been associated with vaccinations. Tetanus toxoid, influenza vaccines, polio vaccine, and others, have been related to phenomena ranging from autoantibodies production to full-blown illness (such as rheumatoid arthritis (RA)). Conflicting data exists regarding also the connection between autism and vaccination with measles vaccine. unquote


As regards the remark on autism: 100 years ago, the incidence of autism was about 1:10,000. Now it is about 1:100.
There is a doctor in the US who has about 3,500 patients who were not vaccinated for measles. The total number of people among them with an autism: ZERO! while you would expect 35!

As regards the link between Hepatitis B vaccinations and MS, the results of a country wide epidemiological study following the mass vaccination campaign against hepatitis B in France show a significant correlation https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4266455/
Or see for instance the video of the Vaccine Safety Conference Session 13 36:30 on https://forbetterscience.com/2019/06/26 ... l-academy/

I was vaccinated for Hepatitis B in 1999 (2x) and 2000 at the age of 44. Three years later I was diagnosed with MS. I think it mainly affects mid-aged people who have a problem with the gut (IBS, EBV Peyer's patches relationship) and who already have 'thin nerves' like me i.e. those people who have other conditions that pre-destine towards MS. I think young people will be less affected.

The role of Toll like Receptors ligands including TLR ligands from the microbiota and vaccine adjuvants are of particular concern. For Hepatitis, I think retro viral elements may contribute through the RNA interference mechanism. This means that different mechanisms may underly or contribute.
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Re: A new concept for MS and other autoimmune diseases

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Copied from the other thread on genetic and environmental risk factors on viewtopic.php?f=1&t=31202

In my case, the left Internal Jugular Vein (IJV) is dominant. Which is a kind of strange. Normally left and right IJVs should be equal. So why is that? That is because the right IJV was blocked already during the foetal phase, a birth defect. During the foetal phase, the left IJV grew larger, to compensate for the blockage on the right.
The blockage of the right IJV was a truncation, almost the perfect truncation as in the text books. I still keep a picture of the situation before it was opened, from before I was liberated from CCSVI.

My family lived for generations in the shadow of the heavy metal industry. So yes, location matters.
The studies from the industrial cluster south of Boston and from Texas (that you may find earlier on this thread) show a clear causal relationship between living in the vicinity of the heavy metal industry and vascular insufficiencies, insufficiencies that may even be passed on from generation to generation.
In our small countries over here, evidence of the relationship between MS, vascular insufficiencies and the heavy metal industry is at best anecdotal. From the nurse who moved from Leeuwarden, a small provincial town in the north of The Netherlands, to Beverwijk, a town of similar size in the west and in the shadow of the heavy metal industry. Where in Leeuwarden there were a few MS patients in the whole town, in Beverwijk she found several patients in each suburb. Or in Belgium where one MS center is located close to Brussels, a metropolitan area with millions of inhabitants. As you would expect. But then there is another one, in Overpelt, close to the Dutch border, in a rural area. So why is that, why there? The heavy metal industry was concentrated there and they may have seen a relatively high number of MS cases in the area.
In fact, I was born on the other side of the border, at half a mile from the borderline where, as a young kid in the 1960's, I saw the chimneys spreading their dark dust and ashes over the area.

My grandfather died from a NasoPharyngeal Carcinoma which is rare on our lattitudes and which I attribute to a weakened immunity of the nasopharynx. Why? Exactly, because of hypoperfusion due to IJV blockage. Which defect was then genetically passed on to me.
My two eldest children don't have it, they were checked by the best doctor who must have seen and liberated over a 1000 MS patients. My youngest daughter still needs to be checked.

Pitty that CCSVI was completely denied or ignored by neurologists and the medical sector. Because it is most definitely a factor that may lead to MS. But yes, I would agree, the situation is complicated and the cascade is long and bring us back billions of years to the origins of the development of biological life.

Why did I get MS? It must have started with the blocked IJV. And after BBB breach, herpes found its way. And I got neurological symptoms. But my immune system dealt with the situation. Until a bad gut developed at mid-age - there may be some relationship with EBV working on Peyer's Patches and causing IgA deficiency. And epigenetic control weakened. But even then, my immune system managed. But the nerves must have been 'thin'.
Then, around 2000, I was vaccinated three times for Hepatitis B. At the age of 45. Three years later there was the big flare up and I was diagnosed with MS. Why? Adjuvants may have been a factor but it is more likely the vaccination introduced a virus (possibly a smaller retro virus carried by the double stranded Hepatitis B virus) that entered cells, folded, was cut into pieces and fragments then fitted on open genes that then changed cell function. Cells came to expression and T cells came to rescue and caused the flare up and the lesions. And all the rest followed, including an acceleration of the progressive phase - a progressive phase that we all have and is a normal part of aging but now was accelerated because of iNOS at lesion sites and muscular hardening because of insufficient and diffuse muscle control. [To note here as well that a high EBV B cell concentration which is also part in progression is seen in many people, not only in MS patients, and may even have some protective effects]
Which is all explained in the above postings on MS and autoimmunity.

Is this all delusional thinking? I don't think so. I firmly believe that this is what caused my own MS. And I think that my case is not unique here, that there will be many MS patients like me.
Last edited by Leonard on Mon Jan 13, 2020 10:56 am, edited 6 times in total.
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Leonard
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Re: A new concept for MS and other autoimmune diseases

Post by Leonard »

Our understanding of the cellular biology is focussed on the energy metabolism; the evolutionary path of our cells is described under undisturbed physiological conditions. But in reality, cellular development took place under very unfriendly and harsh conditions, with agression of bacteria, viruses and fungi. Some of these pathogens may even be species from an ancient RNA world that preceded our DNA world. Therefore, besides the energy metabolism, it may be assumed that our cells developed highly sophisticated internal mechanisms to deal with foreign pathogens as viruses and retroviruses, right from the very beginning and that these mechanisms are fully integrated with the cell’s machinery and are as important as the ATP energy cycle.

I wish to focus here on the anti-viral properties of our cells which seem most important in the context of auto-immunity and MS. This article on “Effects of Interferons and Viruses on Metabolism” reviews our knowledge on the immune metabolism. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5174094/ But as the article in its concluding remarks rightly suggests, we could turn around the title as follows: “Effects of Metabolism on Interferons and Viruses”. As such, individual metabolic pathways may be important for specific immunological functions. The article adds that more study is needed to elucidate whether a metabolic shift is the cause or the consequence of a change in cellular phenotype. The article then concludes that the reciprocal regulation of interferons and metabolic processes advances our understanding of the immunometabolism and may hold future surprises for our understanding of immunity in health and disease.

As regards the direction of causality, I tend to believe that a shift of the energy metabolism causes a change of cellular phenotype. Identical twins that get separated and relocate before adolescence (= main phase of cellular growth) have different risks to develop MS. The reason is that the one who moves further south will have more sunshine, higher vitamin D, more mitochondria per cell and a better ATP metabolism [postscript: and better mitochondrial fitness; latest insights suggest that mitochondria are involved in pathologies, not just in energy production and metabolites for growth. Mitochondrial fitness determines cell fate and cell function. See e.g.
on Mitochondria control of physiology and disease: beyond ATP ]. The increase in ATP and mitochondrial fitness and number will support the energetic demands of high cytokine and interferon production upon viral infection [postscript: and also the quality of mitochondrial signaling].

The other person will have a reduced mitochondrial respiration which may lead to the accumulation of succinate which in turn can drive NO and mitochondrial ROS production, a conserved response of evolution against many pathogens. In this down regulated scenario, the viral infection will lead to cell damage and death; in the upregulated scenario, several hundred interferon stimulated genes will inhibit viral replication. So in other words, the issue is one of viral clearance versus tissue pathology, or; while one remains healthy, the other will get sick, exactly as we see with MS. SNPs or combinations of SNPs have a critical role in mitochondria anti-viral signaling (MAVS) and to alert the innate immunity.

The article provides for an interesting reading as it brings the generation of NO (NOS2, iNOS) and the formation of peroxynitrite into the picture (possibly in combination with superoxide from EBV B cells). The article also elaborates on interferon-mediated metabolic effects by epigenetic modifications such as methylation. In other words, some cells become more vulnerable than others if the epigenetics goes wrong because of gut microbiome insufficiency.

Hence, the article fully aligns with the above essay on autoimmunity and our society viewtopic.php?f=1&t=15188&p=258372#p258372 And combined we may see here the seeds of a whole new grand theory on health and disease.
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Leonard
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Re: A new concept for MS and other autoimmune diseases

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A perspective on the link between mitochondrial functioning and disease

Most of our body’s nucleated cells contain 500 to 2000 mitochondria, some sources say 1500 to 3000, the heart muscle up to 5000. In the cone cell photoreceptors of the eye, mitochondria make up 80% of the intracellular volume. In extraocular muscles like the lateral rectus, they account for 60%, and in heart muscle they comprise 40% of the volume of the cell. Mitochondria are the only cellular organelles in animals known to have their own DNA, distinct from the nuclear DNA, maternally inherited. It is thought that mitochondria became an integral part of eukaryotic cells more than two billion years ago when the oxygen concentration in the earth's atmosphere sharply rose, giving the cells the ability to fuel a much more efficient way of releasing energy.

Mitochondria play a vital role in bioenergetic and biosynthetic pathways and can rapidly adjust to meet the metabolic needs of the cells through mitochondrial biogenesis and fusion of individual mitochondria into dynamic networks. A decrease in demand then results in the removal of superfluous mitochondria through fission and mitophagy. Mitochondria frequently fuse and divide potentially allowing wild-type mitochondria to compensate for defects in mutant mitochondria by the transfer of wild-type RNA. Mitochondria signal into the nucleus and as such may determine cell fate and cell function (ROS).

Malfunctions of mitochondria are thought to be associated with a host of serious neurodegenerative and other chronic diseases. Therefore, overall mitochondrial fitness may be an important factor in health and disease. Fit mitochondria will provide robust metabolic pathways, mitochondrial function and metabolism-related signalling pathways. Upregulation of several hundred interferon stimulated genes inhibits cellular and viral translation, inhibits protein expression and viral replication. In less fit cells, viral proteins may interfere with signalling pathways subverting its anti-viral effect, causing an evasion of host cell immune response and, in the end, even virus control of host cell metabolic activity. (Ref. 1 - 4)

Innate immune responses are the first line of defence that protects the host from viral invasion. What is relatively new is that mitochondria take center stage in this cellular antiviral immunity. Little is known about the effect of the quality of mitochondrial antiviral signalling protein (MAVS) on diseases. It appears that MAVS variations may result in serious diseases. Single Nucleotide Polymorphisms (SNPs) in MAVS are functionally associated with susceptibility to viral infection and altered antiviral signalling is seen by MAVS SNPs. (Ref. 5)

Cellular innate immunity is highly complex. With multiple signalling pathways to systemic immunity, the picture becomes even more complicated, see for instance the numerous immune cell subsets in Fig. 7 of Ref. 6. And when there is something impaired, the system is trying to compensate in many ways. For instance, oxidative stress may activate genes that act as a brake for T cells (Ref. 7). What is correlative, which genes are upregulated and which genes are downregulated, what sort of reaction, what reciprocal regulations, with the number of permutations growing, the complexity is staggering…

I think that the vitamin D level (= sun exposure and cholesterol) during the main phases of cellular growth (foetal phase and adolescence) is an important factor that determines mitochondrial fitness (and number). In fact, this seems confirmed by the risk of developing MS in identical twins that were separated and the critical time when this separation must have occured. Cellular anti-oxidant activity (activity of enzymes and gut-provided metabolic intermediates) may also be an influence that determines mitochondrial fitness.

My experience also tells me that the reaction of the immune system to foreign pathogens is a ‘measured reponse’. In innate immunity, the cell will hold back the (interferon) trigger if beneficial. The task to be performed is to clear the infected tissue with minimal damage done. I think over many hundreds of millions of years of evolution the system has learned to limit as much as possible damage done, to achieve the best possible outcome for the patient. For example, the response to herpes (autoimmunity in Ref. 8 ) may be different to the response on Hepatitis B (virus infection in Ref. 8 ), the former being more mild. This points to different patterns in MS plaques, depending on the type of pathogen and the specific immune reaction. This is indeed what is seen.

I think we should now put it all together in the big melting pot and develop a new grand theory on health and disease. Let us liberate old structures and build a new knowledge community.

Ref. 1: Virus Control of Cell Metabolism for Replication and Evasion of Host Immune Responses
https://www.frontiersin.org/articles/10 ... 00095/full
Ref. 2: Mitochondrial double-stranded RNA triggers antiviral signalling in humans
https://europepmc.org/article/PMC/6570621
Ref. 3: Functional Mitochondria in Health and Disease
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5675848/
Ref. 4: Mitochondrial Dynamics: Coupling Mitochondrial Fitness with Healthy Aging
https://www.sciencedirect.com/science/a ... 1417300035
Ref. 5: Alteration of Antiviral Signalling by Single Nucleotide Polymorphisms (SNPs) of Mitochondrial Antiviral Signalling Protein (MAVS)
https://journals.plos.org/plosone/artic ... ne.0151173
Ref. 6: Multiplexed imaging of immune cells in staged multiple sclerosis lesions by mass cytometry
https://elifesciences.org/articles/48051
Ref. 7: Activation of genes linked to “oxidative stress”
https://news.ki.se/unexpected-effect-of ... 1577123303
Ref. 8: Heterogeneity of multiple sclerosis lesions: Implications for the pathogenesis of demyelination
https://www.researchgate.net/publicatio ... yelination
Last edited by Leonard on Fri Feb 28, 2020 1:57 am, edited 14 times in total.
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