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-
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. email@example.com
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.