Theoretical Immunology

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Leonard
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A common cause for a multitude of autoimmune disorders

Post by Leonard »

Following the recent ECTRIMS meeting and youtube reports on the all important role of the gut in autoimmunity,
I googled a bit on "gut induced autoimmune" and found many very interesting articles.

This article is top as it brings together many of the aspects that we have touched upon here before but then from a slightly different angle and perhaps more professional perspective. Amongst others, it reports about an experiment where researchers induced autoimmune disease by introducing specific bacteria to the gut, and resolved it by introducing another, making a compelling argument for a causal relationship between the gut microbiota and autoimmune activity. There is also a good explanation of the role of Vitamin D in progressive MS. The article is a must read for all who have followed this thread and agree to the broad lines that are seen to emerge from here.

http://www.townsendletter.com/June2012/ ... e0612.html

I can see MS as a collection of symptoms with a strong commonality in the gut, moving around somewhere in the space between lectins, protoxin, microbial peptides common to several major classes of bacteria, anti-microbial action and anti-microbial peptides and the like. And it all communicates together in some way. As a complex it is believed to be the underlying cause of many/all 'autoimmune' diseases. Where years of strict diet can change its course as has been shown by Swank, MacDougall, Walhs etc. Obviously, as far as MS is concerned, ccsvi is an important disease-enabling factor as explained before.
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Leonard
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Re: A new concept for MS

Post by Leonard »

http://americannewsreport.com/nationalp ... 22102.html

The article talks about the acute MS disease process. For this 21 year old woman, an acute attack is most likely as she is below mid-age and the gut lining has not yet become porous.

Unlike suggested by the article, I think that the acute relapse is an issue of receptor blocking by bacteria such as Cpn or virus such as EBV which quickly degrades nutritional conditions and ion-pump charging. But the acuteness of the relapse would not seem to point to real biological changes. The immune system just removes the infectious agent and we see remittance.

However, I think the bacteria is a good candidate for explaining the progressive phase of MS, the slow degeneration of myelin and axons. E-toxins are released, the OPC (Oligodendrocytes Precursor Cells) are affected and don't do their work anymore, and the myelin and axons slowly disintegrate. This is likely a process that affects both the CNS and the peripheral nerves. The typical time constant of that process - a biological process - is not acute, is not days or weeks, but many months or even years. Where the toxin hypothesis would seem to fit neatly with the slow biological degenerative process.

If there are people reading here who have contact with the institute that did this research, please tell them because the understanding of fundamentally different underlying mechanisms causing acute and progressive/degenerative MS may greatly help them to advance their thinking. In the case of this 21 year old woman, it can not be excluded at all that the acute relapse was caused by receptor blockage where the type of infectious agent may have had some relation with Clostridium Perfringens but may also have been related to others that occurred simultaneously.

Besides their association with nervous system cell membranes and their effect on myelin production, the E-toxin is also accumulating in the kidney. What is interesting here is this article suggesting the kidney contributes to host defence against the E-toxin. And maybe, it is a maybe, the urgency to urinate in MS is related in some way as well to this defence mechanism.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC187324/
http://www.jbc.org/content/276/19/15736.abstract

The progressive form of MS would then seem operate as follows:

- the gut is out of balance, too much Clostridium Perfringens type B / D of that gives E-protoxin, 33 kDaltons, which penetrates the permeable intestinal wall;

- the problem of the permeable intestinal wall is caued by something else e.g. by food, gliadin = gluten, fat, sugar. Fat and sugar could also contribute to the imbalance of the gut micro-biome. If it is the gliadin that is the issue, the relationship with lectins that was suggested before and resulted from its relation with the gliadin may need rethinking;

- as the E protoxin leaks into the circulation and is turned into potent toxin by enzymes etc (becomes a 1000x more toxic), the toxin attaches to the OPCs that maintain the myelin / axons. I saw an article that suggested that the broken BBB is important here again. The OPCs will not work properly anymore and the nerves degenerate slowly, year after year.

There was a little discussion about a pure medicine directed approach for myelin recovery on another webforum. While it can help to get quick recovery, it is probably not enough. Treatment of the gut unbalance by antibiotics/fecal transplant (as Borody has shown and as practiced frequently around the world for Clostridium Difficile) would seem to usefully complement the case.

I have updated the new concept on page 1 accordingly.
Last edited by Leonard on Tue Nov 05, 2013 3:11 am, edited 1 time in total.
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What is happening in the micro-cosmos of the endothelium?

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What is happening in the micro-cosmos of the endothelium?


http://www.ncbi.nlm.nih.gov/pubmed/21518257

quote: The crystal structure of ε-toxin reveals similarity to aerolysin from Aeromonas hydrophila, parasporin-2 from Bacillus thuringiensis and a lectin from Laetiporus sulphureus. Like these toxins, ε-toxin appears to form heptameric pores in target cell membranes. The exquisite specificity of the toxin for specific cell types suggests that it binds to a receptor found only on these cells.

What do we learn from here?

Lectins and E-toxin are similar in structure and molecular weight.

They attach to the membranes of target cells and form pores, as discussed before for the lectins.

Apparently, E-toxin binds to a receptor found only on specific cells. Could this be OPCs?


http://www.plosone.org/article/info%3Ad ... ne.0076359

quote: Although ETX binds to peripheral nervous system (PNS) myelin, as it does CNS myelin [25], autoradiograph studies show that ETX only targets the CNS and not the PNS [74]. We propose that ETX fails to bind to PNS endothelial cells that comprise the blood-nerve barrier; therefore PNS myelin is not exposed to the toxin.

Finally, binding of ETX to retinal veins that form the blood-retinal barrier (BRB), a CNS barrier analogous to the BBB, may explain the enigmatic observation of periphlebitis retinae in people with MS [55], [56]. The human retina is typically devoid of myelin, yet vascular scarring occurs [75]. Primary ETX action on the BRB may result in retinal phlebitis that is independent of oligodendrocytes or myelin. Furthermore, serum protein leakage and the accumulation of perivenular monocytes in the absence of oligodendrocyte apoptosis or demyelination are often observed in pathologic MS brain specimens [6]. These observations may similarly be due to subtle insult of the endothelium and a secondary innate immune response.

What do we learn from here?

E-toxin fails to bind to [PNS] endothelial cells that compromise the blood-nerve barrier. May we extend this to the CNS/BBB?

Is the broken BBB important here again, establishing the necessary condition that would allow ETX binding to endothelial cells?

Is our nerve degeneration all about an insult of the endothelium and how does that relate to OPC working? And to mitochondrial energy supply? And to ion pump charging?


This article is very recent.
http://link.springer.com/article/10.100 ... 8-9#page-1

On cross talk between cerebral endothelium and oligodendrocyte

quote .... interactions exist between cerebral endothelial cells and oligodendrocyte lineage cells.
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what seemed black and white turns into many shades of gray

Post by Leonard »

For decades, the medical sector has studied the individual organs in great detail. The effects of individual organs are well known. Everybody concentrated on his specific piece of the pie; it was not done to look across into the competency of others. This had led to a huge systemic failure.

The study of the effects of individual organs should not be divorced from the meta-level analysis, neither conceptually, nor in time. They must be viewed together, one can learn from the other and vice versa. I will give you an example.

Look at the double peak in the graph of age or onset of MS. That is a fact, at the meta-level. This was explained by neurologists even in 2011 as an imperfection in the statistics. But that is not so. My contention is that the second peak arises because after mid age a fundamentally different mechanism kicks in, that of an unbalanced permeable intestine. And this meta-level thinking of fundamentally different underlying mechanisms changes the whole appearance of MS, and with that the search for possible effects of organs on MS.

I now think that MS in the second progressive phase is - again – caused by different underlying mechanisms. Patients with MS may suffer from constipation possibly caused by Clostridium Difficile in the large intestine, or from spastic colon possibly caused by Clostridium Perfringens B in the large intestine, or a CYP450 enzyme deficiency in the small intestine, or a combination of all of these. Along with a permeable intestine, it is these 'imbalances' that cause lesions in the white matter. We see here a strong overlap with diseases such as mitochondrial energy failure where patients with mitochondrial energy failure have exactly the same lesions and intestinal problems.

In our specific case (MS), the consequences of ccsvi may give specific problems such as walking difficulties (longest neurological pathway) and possibly we have got some more lesions close to the outlet (drainage) whereas patients with mitochondrial energy failure - who also have the broken / unbalanced gut but not ccsvi - have very similar problems with muscle control but probably less neuro-disconnection in those places in the brains where the effects of ccsvi were felt the most. And what once seemed black and white turns now into so many shades of gray...

Several years ago, my brother was diagnosed with a mitochondrial energy failure, or at least it looks highly likely (diagnosis is positively confirmed only in 40% of cases). The incidence was 1:4000 but that is probably on the rise as a well. Now, there is a strong genetic component in the disease i.e. the possibility that brothers and sisters get the same disease (don't worry, it is not in the brains, it is the gut). Against this background, his diagnosis and my MS diagnosis were reassessed and both were confirmed. He does not have MS; I do have MS. Our symptoms are largely the same. But I have more difficulty walking; he does better. I have more energy to bike for 15 miles; he has less.

The problems concentrate in the gut. An IgG ELISA test to determine individual food intolerance may become a very important starting point for getting control on our diseases. But then the systemic failure is felt again: because I have MS I should see the neurologist... It remains an uphill struggle.
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autoimmunity is in the gut – the GAPS protocol

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I invite you all to look at these websites:
http://gaps.me/
http://www.doctor-natasha.com/
http://theglutensummit.com/natasha-camp ... d-mmedsci/
http://theglutensummit.com/

Dr. Natasha Campbell (neurologist and nutritional expert) gave a very convincing presentation at the Gluten Summit, namely that all autoimmunity is developing in the gut and that with a good diet it takes six months to a year before that autoimmunity has calmed down. She stressed that it is possible to heal the gut and normalise the immune system! (above link on glutensummit refers).

On the Gluten Summit, there was also the story of Dr. Hadjirassiliou who said that there are still questions about how autoimmunity is triggered in the brains and he mentions two things: the BBB and the cerebrospinal fluid. Of course, as patients we know very well where things go wrong: ccsvi is a necessary condition for MS to develop. On the breached BBB, we know. On the cerebrospinal fluid, these links are interesting:
http://journals.lww.com/neurosurgery/Ab ... re.21.aspx
and Joan's comment: http://ccsviinms.blogspot.nl/2012/11/no ... -once.html

I think that the GAPS Practitioners are the neurologists of the future (go to http://www.gaps.me and then in the right column you can search for a GAPS practitioner in your area). This alternative view of MS must now quickly turn into main stream, the establishment fade into the background. As Natasha Campbell says in her presentation, that will happen once. But there is so much to gain from a fast turnaround.

I do not think that MS has many secrets anymore; the problem is a huge systemic failure. The weight of the status quo is so immense that any call for change risks to collapse under that weight. I wonder what else we could do to get change underway..
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Re: A new concept for MS

Post by PointsNorth »

Hi Len,

And to close the loop - vit. D deficiency and gluten intolerance. Much here!

http://www.healthnowmedical.com/blog/20 ... eficiency/

Best, PN
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My Current Regimen http://www.thisisms.com/forum/regimens-f22/topic25634.html
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Re: A new concept for MS

Post by Leonard »

Thank you PointsNorth for your comment, very appropriate.

The video's from Dr. Kaplan on celiac disease also mention Vitamin D is an issue.


In fact the whole series of 7 parts is very worthwile to look at (just go to the above link and you find them).
It explains it all, many of the things we have seen before (cortisol, thyroid, stress etc etc) are put in context here!
I like the way he talks, the confidence in his voice and appearance.

I think if you would replace celiac disease with gastro-intestinal inflammation in general (for what ever reason this may be caused), you get very close to the root cause of our problem.
Last edited by Leonard on Sun Nov 17, 2013 11:42 pm, edited 1 time in total.
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Re: A new concept for MS

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http://www.ottawacitizen.com/health/Ott ... story.html

This is absolutely great!! The more dust this case causes, the better it will be for us. A jury trial could help turn around the whole picture, for the whole world...

It is a case we can not loose. Perhaps technically, in a pure legal sense, but morally we will always prevail. I hope the case will lead us to a new sense of things, conceding that significant systemic problems are pervasive and have hampered the course toward profoundly changing the autoimmune paradigm.
Last edited by Leonard on Sun Nov 17, 2013 11:38 pm, edited 1 time in total.
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Re: A new concept for MS

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I know this is totally off topic... Could someone point me in the right direction of how to use pm in the outbox?
Thank you
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Re: A new concept for MS

Post by Leonard »

With ref to the last posting, I'm in contact with Ann.

The medical sector better hurries up and starts to communicate openly and honestly with us because otherwise we - that is the patients - will have solved the problem before them...

Unfortunately I can not get back the presentation of Natasha Campbell that she gave at the Gluten Summit (it was in the open but now you have to pay for it..). It was not about gluten, it was about autoimmunity and how it all starts in the gut, and how you can heal your gut and normalise your immune system. It was just wonderful! Also the above presentations by Dr. Kaplan are great.

Whether it is lectins, Epsilon protoxin, or mimicry, is not very important either. What counts is that you can reverse things and stop the immune attacks. By a healthy gut, that restores the normal gut permeability and calms down the immune system.
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Re: A new concept for MS

Post by MSandI »

Hi Leo
I truly like the way you think. Do you believe that a leaky gut can be repaired through diet so that is not an issue anymore?
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Re: A new concept for MS

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MSandI wrote:Hi Leo
I truly like the way you think. Do you believe that a leaky gut can be repaired through diet so that is not an issue anymore?
Ann
You might be interested in the following post.

http://www.thisisms.com/forum/diet-f9/t ... ml#p213472
Leaky Gut and an Immune System Run Amok

The People's Pharmacy recently interviewed a mother of a three your old son who was diagnosed with juvenile idiopathic arthritis. The doctors had put her son on methotrexate, but the side effects were too much especially for a three year old. Instead, she tried treating him for leaky gut syndrome (intestinal permeability) using diet and supplements. After some time, her son, who had needed help getting out of bed due to pain in his joints, was up and running around again.

The interview will be freely available for about the next 3 weeks.
http://www.peoplespharmacy.com/2013/07/20/911/
The interview is still available at this time.
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Re: A new concept for MS

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Thank you NHE, very informative
Ann
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Re: A new concept for MS

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http://www.medicaldaily.com/parkinsons- ... ent-259364
quote: At the peak of disease, when the mice were most severe paralyzed, in just a number of days, you could almost not tell them from regular mice.

I found this article on the possible use of a Parkinson drug for MS on TIMS on the subject called Drug pipeline.
The article sounds quite hopeful where I do not exclude the possibility that something like this could indeed work for us.
Notwithstanding, the leaky gut will have to be addressed at the same time as otherwise they are pumping the ship without fixing the hole. If they would however help us fix the leaky gut, you may be able waning of yourself of the medication after sometime when the autoimmunity has been put to rest. And in reply to the question asked before, yes I think that it is possible to restore a healthy gut by good diet but it takes time, half a year to a year.

On the issue of a healthy gut, you may wish to have a look at these video's.
I know they do not quite substitute for the excellent presentation that Dr. Campbell gave at the Gluten Summit (unfortunately not available anymore under open access), but it shows the gist of the thinking...

http://articles.mercola.com/sites/artic ... -gaps.aspx
http://healthyprotocols.com/2_DOCTOR%20Natasha.htm

Dr. Campbell is right about the Sauerkraut, the antibiotic effects of fermented foods etc.
But I think there is a further dimension to it and that is the mineral content of our foods. This links in with the diet proposed by Terry Wahls, to eat lots of coloured vegetables and fruits. In a Dutch textbook, I found this table comparing the same foods in 1940 and 1990. It is actually quite alarming:

Food Decrease

Carrot Mg 75%, Ca 48%
Broccoli (cooked) Fe 46%, Cu 75%
Union Ca 75%
Spinach (cooked) Fe 60%, Cu 96%
Kohlrabi Fe 71%

Less minerals, perhaps less vitamins, less fytonutrients.
This is comparing 1940 with 1990. Not to think about 2013. It won't have gotten any better...

McCance RA & Widdowson EM (1940) The Chemical Composition of Foods, Medical Research Council Special Report Series No. 235. His Majesty’s Stationery Office: London.

Kirk RS & Sawyer R, ed. (1991) Pearson’s Composition and Analysis of Foods, 9th edn. Longman Scientific and Technical: Harlow, UK.

http://www.webmd.com/diet/phytonutrients-faq
http://en.wikipedia.org/wiki/Food_compo ... cite_ref-7

An other interesting issue is related to our high grain consumption. We know about the gluten problem, this was addressed before, but there may be an additional problem namely that our high grain consumption leads to extra mineral deficiencies. Phytates in grain bind minerals which then are not absorbed any more by the gut.

So you need a healthy gut lining (to make sure nothing gets in that does not belong there) with a good balanced bacterial content (to make sure vitamins are produced and micronutritients are absorbed). And your diet needs vegetables and fruits of high quality. It was said that the absorption of minerals from food is 1000 times more efficient than from supplementation.

But quality in our western food chain is average/low and added to that there is much refined carb in our diet which aggravates mineral absorption. And when taken all together, this may help explain the surge of (autoimmune) diseases in our western society where mitochondrial energy failure is probably an important component.

Last week, it was in the news that 5 million people in the Netherlands have some form of chronic disease; about one third of the total population. I am sure a majority of these people will have some form of autoimmune disease. Probably, it is not very different in the US or Canada or any other European country. In any event, if there is only a grain of truth in the above postings, I think there is quite some work to do.
Last edited by Leonard on Wed Jan 22, 2014 8:30 am, edited 1 time in total.
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Re: A new concept for MS

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GMOs linked to gluten disorders plaguing 18 million Americans - report
Published time: November 26, 2013 20:20
Edited time: November 27, 2013 06:28
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From Russia Today web site.

AFP Photo / Khaled Desouki
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Food, GMO, Health, Science, USA
Genetically modified foods such as soy and corn may be responsible for a number of gluten-related maladies including intestinal disorders now plaguing 18 million Americans, according to a new report released on Tuesday.
The report was released by the Institute for Responsible Technology (IRT), and cites authoritative data from the US Department of Agriculture, US Environmental Protection Agency records, medical journal reviews as well as international research.
“Gluten sensitivity can range in severity from mild discomfort, such as gas and bloating, to celiac disease, a serious autoimmune condition that can, if undiagnosed, result in a 4-fold increase in death,” said Jeffrey M. Smith, executive director of IRT in a statement released on their website.
Smith cited how a “possible environmental trigger may be the introduction of genetically modified organisms (GMOs) to the American food supply, which occurred in the mid-1990s,” describing the nine GM crops currently on the market.
In soy, corn, cotton (oil), canola (oil), sugar from sugar beets, zucchini, yellow squash, Hawaiian papaya, and alfalfa, “Bt-toxin, glyphosate, and other components of GMOs, are linked to five conditions that may either initiate or exacerbate gluten-related disorders,” according to Smith.
It’s the BT-toxin in genetically modified foods which kills insects by “puncturing holes in their cells.” The toxin is present in ‘every kernel’ of Bt-corn and survives human digestion, with a 2012 study confirming that it punctures holes in human cells as well.
The GMO-related damage was linked to five different areas: Intestinal permeability, imbalanced gut bacteria, immune activation and allergic response, impaired digestion, and damage to the intestinal wall.
The IRT release also indicated that glyphosate, a weed killer sold under the brand name ‘Roundup’ was also found to have a negative effect on intestinal bacteria. GMO crops contain high levels of the toxin at harvest.
“Even with minimal exposure, glyphosate can significantly reduce the population of beneficial gut bacteria and promote the overgrowth of harmful strains,” the report found.
Dr. Tom O’Bryan, internationally recognized expert on gluten sensitivity and Celiac Disease, says that “the introduction of GMOs is highly suspect as a candidate to explain the rapid rise in gluten-related disorders over the last 17 years.”
Internist, Emily Linder, offered some backup for the report’s findings. She removed GMO from her patients’ diets, finding that recovery from intestinal diseases was faster and more complete.
“I believe that GMOs in our diet contribute to the rise in gluten-sensitivity in the US population,” Linder said in the release.
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