Immune system activation in CCSVI

A forum to discuss Chronic Cerebrospinal Venous Insufficiency and its relationship to Multiple Sclerosis.

Immune system activation in CCSVI

Postby cheerleader » Sun May 17, 2009 7:59 am

Marie is on the road, and NHE brought up some important points regarding the immune system, autoimmunity in MS, and how this may fit in the model of CCSVI. Here are NHE's thoughts...
http://www.thisisms.com/ftopicp-57620.html#57620

I am of the opinion that the immune activation is secondary to venous insufficiency , that it is a response, and the "autoimmune" reaction of MS will be halted once venous insufficiency is corrected. It will be interesting to see Jeff's MRIs after his stent procedure, since he is relatively treatment naive (copaxone 2 years.)

To back this supposition up- we need to look at other diseases linked to venous insufficiency- and study how the immune system is activated-

Scleroderma
link

Chronic venous insufficiency - a potential trigger for localized scleroderma.Ludwig RJ, Werner RJ, Winker W, Boehncke WH, Wolter M, Kaufmann R.
Department of Dermatology, Klinikum der Johann Wolfgang Goethe Universität, Theodor-Stern-Kai 7, Frankfurt am Main, Germany. r.ludwig@em.uni-frankfurt.de
Localized scleroderma is a cutaneous disease that is characterized by an initial inflammatory response, followed by sclerosis of the skin. The cause of localized scleroderma has not yet been determined. Seifarth et al. reported two cases of localized scleroderma at sites of chronic venous insufficiency. We document here three more patients in whom localized scleroderma was located at insufficient veins. Treatment of underlying chronic venous insufficiency (CVI) leads to a substantial clinical improvement of scleroderma at the site of insufficient veins, but not elsewhere. Experimental data support the concept of chronic venous insufficiency creating a microenvironment, which may lead to localized scleroderma. Local hypoxaemia, which is present in CVI, induces the release of endothelium-derived cytokines, such as IL-1. Subsequently, expression of endothelial adhesion molecules and consequently leucocyte extravasation are induced. Infiltrating leucocytes secrete a number of inflammatory mediators, including transforming growth factor beta, which is a potent stimulus for collagen synthesis. Therefore, it may well be that CVI is a potential trigger factor for localized scleroderma. In addition, localized scleroderma may only develop if a certain amount of trigger factors are present - and resolves if one or more of the contributing factors (i.e. CVI) can be treated.


It is the initial inflammatory response and hypoxaemia (lack of oxygen) at the site which precedes the autoimmune response

This model is the same in Chronic Venous Insufficiency in the Legs-
An immune-mediated response to severe CVI is an increase in inflammatory cells such as macrophages and T-lymphocytes, which can cause endothelial damage. As CVI progresses, increased microvascular blood flow causes the capillaries to become dilated and tortuous. Increasing hydrostatic forces lead to the accumulation of perivascular and lymph fluids causing edema; decreased oxygenation to surrounding tissues; and skin changes, particularly stasis dermatitis. Hyperpigmentation, an irreversible red-purple hue, is the result of RBCs leaking from the blood vessels and becoming trapped under the skin. Complications of severe CVI result in the formation of thromboses, reducing blood flow and depriving the skin of nutrients and oxygen. The result is ulceration and microedema and, ultimately, the development of venous ulcers.

http://www.accessmylibrary.com/coms2/su ... 791597_ITM

Dr. Zamboni put all of this together in his paper The Big Idea-
Here, Zamboni traces the path from iron deposition to inflammation to damage and immune activation.

From Marie's write up on the sticky:
There are a variety of materials in that link related to venous cause of MS, the Zamboni paper is the second one down and it outlines the hypothesis of how MS might be caused by venous insufficiency. This paper starts the journey for the Ferrara team forming the basis for the idea that MS might be related to venous issues and setting the stage for later research to see if that is correct or not. The other materials on that "lab project" paper are worth reading as well.

http://www.physics.ubc.ca/~rauscher/labproject.pdf
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Postby cheerleader » Sun May 17, 2009 12:49 pm

Another thought on the immune system and CCSVI...

Zamboni noted in the 2008 study, that every MS patient tested, whether on immune modulating medication or not, HAD STENOSIS in the jugular and/or azygos veins. There was no difference between treated and non-treated patients in the levels of blockage.

Jeff was treated with Copaxone for two years, and had bilateral jugular stenosis.
If the "faulty immune system" is the initiating event in MS and CCSVI, than why doesn't immune modulating medication result in the clearing of stenosis?

It will be interesting to see if patients who have had complete immune ablation still have stenosis.
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Re: Immune system activation in CCSVI

Postby NHE » Sun May 17, 2009 2:32 pm

Hi Cheerleader,
cheerleader wrote:Marie is on the road, and NHE brought up some important points regarding the immune system, autoimmunity in MS, and how this may fit in the model of CCSVI. Here are NHE's thoughts...
http://www.thisisms.com/ftopicp-57620.html#57620

I am of the opinion that the immune activation is secondary to venous insufficiency , that it is a response, and the "autoimmune" reaction of MS will be halted once venous insufficiency is corrected. It will be interesting to see Jeff's MRIs after his stent procedure, since he is relatively treatment naive (copaxone 2 years.)


I think that you may have misread my post. I'm actually in agreement with you. I think that CCSVI presents itself as a reasonable hypothesis for having a role in the initiation of the immune system's attack against myelin and not the other way around.

Though, I wonder if the immune system will give up its assault so easily. It may indeed be the case that fixing CCSVI related stenosis will stop the immune attack. However, MS patients have been found to have misregulated genes which are important in the process of apoptosis. This could be part of the genetic predisposition found in MS patients. In contrast, it could also be due to the chronic activation of the immune system. Please see the links on this subject from one of my prior posts...

NHE wrote:There are also some links to the misregulation of the BCL gene family leading to a faulty apoptotic pathway and an increased risk for MS.


My suggestion that patients may need both treatment for CCSVI and an immune modulating/cleanup treatment such as Tovaxin or Revimmune was based on the idea that even after removing any stenoses, the chronically activated and genetically misregulated t-cells targeting myelin proteins may not cease their attack. A treatment such as Tovaxin could help to expedite the healing process after treatment for CCSVI since it was found to reduce myelin reactive t-cells. However, it would be great if a follow-up treatment was not needed and the t-cell gene regulation went back to a more normal level after CCSVI treatment.

In summary, I still think that we are in agreement with eachother regarding the hypothesis on the order of events in MS, i.e., CCSVI followed by immune activation.

NHE
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Postby mrhodes40 » Sun May 17, 2009 5:28 pm

I responded to this on the other thread also
here http://www.thisisms.com/ftopicp-57620.html#57620

But I want to add that this is going to open up a great lot of new research and it will be a fair number of years before everything is well understood.

It should be known that CVI-- the stasis ulcer-- in the leg is not all totally understood even though they know that if it is caused by blockage, removing it results in healing. There is still a lot of reserach into how it happens to begin with, for example people with it have different collagen it seems. I expect that to be going on here as well and because we have so much MS reseach there will be a huge ripepot to peek at. It is going to be fun! I love puzzles...

However, MS patients have been found to have misregulated genes which are important in the process of apoptosis. This could be part of the genetic predisposition found in MS patients.


There is so much research like this--I think all of it will be reevaluated in terms of this new model over the coming years. Some of it will prove to be insignificant to the pathology, and some if it I suspect will be really just oddities. Like the HLA types and things of that nature, perhaps those genes are associated with alleles that regulate endothelial function as well, you know? I'll bet you anything no one looked for tht association, --why would they have done?--, but people will now we can be sure.

Or maybe the apoptosis issue has to do with endothelial function in a way not looked at, and I reference endothelium in regards to the issues of atresia or blockage why was this allowed to grow/occur in the veins leading from the head?

I am getting random so I will quit. marie

ANd that is just the problem; they have'nt been looking at MS from THIS point of veiw, starting there and seeing what these thing mean if anything.
I'm not offering medical advice, I am just a patient too! Talk to your doctor about what is best for you...
http://www.thisisms.com/ftopic-7318-0.html This is my regimen thread
http://www.ccsvibook.com Read my book published by McFarland Health topics
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Postby cheerleader » Sun May 17, 2009 7:10 pm

wow...we agree (??!!??)
Sorry, NHE- guess I've been on the defensive for too long, I have trouble recognizing a convergence of ideas...you're right, we can only wait and see if the immune system gives up the assault.
And thanks to Marie for acting like a true oligodendrocyte, and mending my patchy thoughts :)
Get some rest and let us know how tomorrow goes.
nighty night-
cheer
Husband dx RRMS 3/07
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Postby jimmylegs » Mon May 18, 2009 3:06 pm

an interesting article, may already be in the mix somewhere, but if not..

http://www.jbc.org/cgi/content/full/283/8/5168
Zinc Deficiency-induced Iron Accumulation, a Consequence of Alterations in Iron Regulatory Protein-binding Activity, Iron Transporters, and Iron Storage Proteins
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Postby cheerleader » Mon May 18, 2009 3:22 pm

jimmylegs wrote:an interesting article, may already be in the mix somewhere, but if not..

http://www.jbc.org/cgi/content/full/283/8/5168
Zinc Deficiency-induced Iron Accumulation, a Consequence of Alterations in Iron Regulatory Protein-binding Activity, Iron Transporters, and Iron Storage Proteins


Jimmy!!! Thanks for this. Iron deposition is a big part of Dr. Zamboni's study "The big idea" - how the brain and spinal tissue is damaged by reflux. Zinc supplementation can really help clean up and heal.
Could you start another thread on your research on zinc here at CCSVI? Will be really helpful. I still believe supplements and diet/nutrition continue to play a big part in healing and continued health for MSers...even with stents, Jeff's still following the supp. program you helped us put together. I miss yacking with you!!
cheer
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Postby peekaboo » Mon May 18, 2009 3:54 pm

Jimmy it would be nice to see you on this thread...contributing greatly as usual :)

Great idea Cheer :D
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Postby cheerleader » Sat Feb 06, 2010 4:20 pm

Bump- for those discussing iron deposition.
OK...back to the fam. Just don't want these important threads to be overlooked.
Cheer
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Postby Johnson » Sat Feb 06, 2010 11:41 pm

cheerleader wrote:Bump- for those discussing iron deposition.
OK...back to the fam. Just don't want these important threads to be overlooked.
Cheer


Ha! Good bump.

You are a dynamo. Your Dad could not have a better advocate.

Will you adopt me?
My name is not really Johnson. MSed up since 1993
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Postby cheerleader » Sun Feb 07, 2010 10:51 am

Thanks, Johnson...
My Dad's neurosurgeon and neurologist have been great. They were glad to speak to someone who understood the lingo. It's so strange how life takes you places you never wanted to go or dreamt you'd end up :)
(My son would tell you not to bother getting adopted....I'm a taskmaster and make him shower and pick up his room and stuff...)

I really hope that these threads with actual papers and good discussions will be read and the research will be referred to, rather than getting buried by hyperbole and nasty ad hominem attacks. I'd love it if folks would go back to the oldies but goodies threads by MRhodes (Marie) and bump them. Go to the first posts about CCSVI- some real gems. bump away.

cheer
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Glad to see you back

Postby fogdweller » Sun Feb 07, 2010 2:11 pm

It was great to see you posting I thought you were taking a break.

Wonder why Haake sceduled his workshop for Superbowl Sunday? Canadian I guess.
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