Autoimmunity is not just a theory in MS

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Re: Autoimmunity is not just a theory in MS

Postby CVfactor » Mon Jan 09, 2012 8:57 am

Here is an interesting article that looks at immune reconstruction after HSCT in children:

http://www.ncbi.nlm.nih.gov/pubmed/12621464

So, in children the CD4+/CD8+ ratio becomes normal after about a year (CD8+ population is normal immediately after HSCT).

It looks like the reversal is influenced by age:

The regeneration of CD4+ cells seems to be dependant on a thymic pathway as well as peripheral expansion of mature CD4+ cells.
Age-associated thymic involution restricts the thymic pathway and may be responsible for prolonged depletion in older children and adults.
The recovery ofCD4+ cells has been shown to be inversely correlated to age.


This is due to thymic involution which is a thought to be a decrease in thymic efficency as a person ages:

http://en.wikipedia.org/wiki/Thymic_involution
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Re: Autoimmunity is not just a theory in MS

Postby georgegoss » Mon Jan 09, 2012 10:34 am

Good post, CV. And if my memory serves me correctly this is also very consistent with everything I have read regarding thymus contributory functionality to immune cellular functionality and rcovery following HSCT.

It seems that as one ages the thymus substantially shrinks in size and becomes (for lack of a better term) less efficient and perhaps less useful. I read somewhere that for many old people the thymus may almost dissappear and actually perform virtually no function at all.

So I can easily imagine that immune repretoir recovery is strongly influenced by age.
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Re: Autoimmunity is not just a theory in MS

Postby CVfactor » Wed Jan 11, 2012 8:43 am

Gerorge,

Yes, from what I read the thymus would at some point stop functioning all together. So in my mind I think HSCT should be viewed as a once in a lifetime procedure at middle age because of the length of time it takes for immune reconstruction.

In the last few weeks, I have begun to experience Lhermitte's sign which I never had before. I think maybe HSCT will be in my future if I continue to decline, but I think I will choose the myeoblative method.
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Re: Autoimmunity is not just a theory in MS

Postby georgegoss » Wed Jan 11, 2012 8:57 am

CVfactor wrote:Gerorge,

Yes, from what I read the thymus would at some point stop functioning all together. So in my mind I think HSCT should be viewed as a once in a lifetime procedure at middle age because of the length of time it takes for immune reconstruction.

In the last few weeks, I have begun to experience Lhermitte's sign which I never had before. I think maybe HSCT will be in my future if I continue to decline, but I think I will choose the myeoblative method.

Good point CV. Another good explantation for why older people may want to consider steering toward the non-myeloablative protocol (with the age cutoff usually around 60 for the myeloablative protocol anyway).

Sorry to hear that L'hermitte's is now added to your symptoms. I also had periodic L'hermitte's sign (not often, but noticeable when it did happen, especially when putting my chin near my chest), and following my HSCT it was one of the first symptoms for me that completely disappeared. It's never happened since.
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Re: Autoimmunity is not just a theory in MS

Postby CVfactor » Fri Jan 13, 2012 8:50 am

Here is a new review article that summarizes the evidence that Epstein-Barr virus and Vitamin D deficiency causes MS:

http://www.expert-reviews.com/doi/pdfplus/10.1586/ern.11.97

Multiple sclerosis (MS) is a complex immune-mediated disorder of the CNS, which results from a combination of
genetic and environmental factors and their interactions [1]. Although genomewide association studies have discovered
numerous genetic variants predisposing to MS, the environment exerts a greater influence on susceptibility [2]. That
nurture is fundamental in MS has been known for decades. Monozygotic twins are, at most, 30% concordant, and familial MS risk is
significantly influenced by location and season of birth and the childhood environment [1,2]. Growing evidence lends strong
support to vitamin D deficiency and Epstein–Barr virus (EBV) infection as being key environmental risk factors.
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Re: Autoimmunity is not just a theory in MS

Postby Asher » Fri Jan 13, 2012 11:30 am

Hi CV, I too suffer from Lhermitte's sign, but then in my right knee. HSCT (7 moths post transplantation) has, so far,brought me no relief. How strange this disease is. I buy into the autoimmunity explanation, but the jury is still out as to what it actually is that causes this seemingly irrational Immune response. I also never heard a plausible explanation, consistent with the autoimmunity theory, as to how it is possible that only the right half of my body is afflicted by MS symptoms? This seems so complex that I doubt I will ever live to see this enigma resolved.
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Re: Autoimmunity is not just a theory in MS

Postby CVfactor » Fri Jan 13, 2012 2:22 pm

Hi Asher,

In my mind I believe MS is like a demented puzzle in that you have to have the unfortunate situation of having all of the pieces fall together for it to manifest itself. It is definitely a disease of the immune system but I agree it will probably take many more years to come to a conclusion about all of the factors involed. And once this is known, finding a drug based cure will likely be realized not to be a solution for those already afflicted but should give insight on how to prevent acquring MS and similar diseases in the first place.

Hopefully your disabilities will resolve with time as your nerves try to adapt. But at the worst you can breath easy in the assurance that you have most likely halted the disease. I have already come to grips with the fact that my disabilities are permanent. Now I need to stop further progression.
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Re: Autoimmunity is not just a theory in MS

Postby CureOrBust » Fri Jan 13, 2012 4:33 pm

CVfactor wrote:In my mind I believe MS is like a demented puzzle in that you have to have the unfortunate situation of having all of the pieces fall together for it to manifest itself.
The demented part is that the one who played with it previously lost some of the key pieces, and may of also mixed in a couple of pieces from a different jigsaw! :evil:
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Re: Autoimmunity is not just a theory in MS

Postby Asher » Mon Jan 16, 2012 7:51 am

My hunch is that this Prof is on the right track!

An article published Friday Dec. 23 in the December 2011 issue of The Quarterly Review of Biology argues that multiple sclerosis, long viewed as primarily an autoimmune disease, is not actually a disease of the immune system. Dr. Angelique Corthals, a forensic anthropologist and professor at the John Jay College of Criminal Justice in New York, suggests instead that MS is caused by faulty lipid metabolism, in many ways more similar to coronary atherosclerosis (hardening of the arteries) than to other autoimmune diseases.

Framing MS as a metabolic disorder helps to explain many puzzling aspects of the disease, particularly why it strikes women more than men and why cases are on the rise worldwide, Corthals says. She believes this new framework could help guide researchers toward new treatments and ultimately a cure for the disease.


http://www.medicalnewstoday.com/release ... 1.php#post

I recently saw a video of a lecture by a Prof. (Technion - Israel's MIT equivalent) who researches arterial sclerotic processes and the related immune responses. This lecture triggered my curiosity and I wondered whether this may provide a clue as to what is going on in MS. Fascinating. I hope this article will recieve the attention it deserves from the scientific community.
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Re: Autoimmunity is not just a theory in MS

Postby CVfactor » Mon Jan 16, 2012 10:44 am

Here are my thoughts:

1. MS is a disease that affects a specific portion of the CNS, namely the myelin sheath (white matter) as well as the axons (gray matter).

2. Neurons are spared in MS. If MS was simply a matter of the immune system indiscriminately causing damage to the central nervous system, it seems neurons would be affected more. You would see more symptoms in people that have similar characteristics of Alzheimers which is a disease that only effects neurons (loss of memory of self, friends, family, etc).

Alzheimer’s disease results in extensive damage to the gray matter of the brain, which is basically a buildup of proteins in the brain in the form of “plaques” and “tangles,” which are associated with dying or injured neurons.

3. MS has a specific pattern of disease, hence the EDSS score which looks specifically at these defects:

■ pyramidal - weakness or difficulty moving limbs
■ cerebellar - ataxia, loss of coordination or tremor
■ brainstem - problems with speech, swallowing and nystagmus
■ sensory - numbness or loss of sensations
■ bowel and bladder function
■ visual function
■ cerebral (or mental) functions

4. There is a huge amount of evidence that shows MS is a disease that has genetic as well as environmental components. If MS was strictly genetic (like CCSVI or a metabolic disorder as described above), it would be seen in 100% in identical twins (same DNA). But the reality is that one twin is only 30% as likely to acquire MS if the other twin has MS.

5. The phenotype of MS will not always be the same. Here is a good article on this:

http://www.direct-ms.org/pdf/ImmunologyMS/Frohman%20Mechanisms.pdf

It is also important to recognize that the aggregate contribution of germline genetic variants to the disease course of a given patient with MS may be modest. This is highlighted by observations that the clinical expression of MS may be very different even between monozygotic twin siblings who both have the disease. It is therefore likely that several postgermline events influence the clinical expression of MS.
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Re: Autoimmunity is not just a theory in MS

Postby georgegoss » Mon Jan 16, 2012 12:29 pm

.
Last edited by georgegoss on Thu Jan 19, 2012 8:00 am, edited 1 time in total.
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Re: Autoimmunity is not just a theory in MS

Postby CVfactor » Mon Jan 16, 2012 12:53 pm

My dentist says MS is probably caused by using too much toothpaste. I am switching to baking soda.
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Re: Autoimmunity is not just a theory in MS

Postby lyndacarol » Mon Jan 16, 2012 1:15 pm

CVfactor – switching to baking soda may not be a bad idea. I think the sugar alcohol, sorbitol, in most toothpastes triggers the pancreas to produce extra…… insulin!
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Re: Autoimmunity is not just a theory in MS

Postby Asher » Mon Jan 16, 2012 2:33 pm

Looking forward to hear when any of you come forth with a plausible unifying theory for MS. I laugh a lot and enjoy humor but cynicism has a way of putting me off. I'll go off to focus on my healing process and my toothpaste, I seem to have forgotten that I actually never really liked the concept of mob sourcing and social media.
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Re: Autoimmunity is not just a theory in MS

Postby CVfactor » Mon Jan 16, 2012 4:20 pm

Asher,

Personally I don't develop hypothesis, but many researchers believe MS is caused by a loss of self tolrance.

Also the prevailing theory is that a latent virus causes cross-reactivity of effector T cells in the presence of the virus when it becomes active. This virus remains dormant in the body until it is reactivated. This is the premise behind the relapsing-remitting phase of the disease. The main candidate virus is Epstein-Barr a.k.a. human herpes virus 4 (HHV-4).

There is a immune cell called regulatory Tcell (or Treg) which was discovered in the last decade who's purpose is to moderate immune responses and shut them down when they get out of control to prevent autoimmunity. These cells have been found to be less effective and/or less numerous in people with MS. In addition it has been shown that vitamin D has a direct affect on these regulatory T cells in terms of development and/or function.

Here is one of many papers that describe a unified theory for MS that incorporates all of these aspects:

http://www.ncbi.nlm.nih.gov/m/pubmed/18387750/

A unifying multiple sclerosis etiology linking virus infection, sunlight, and vitamin D, through viral interleukin-10.

Hayes CE, et al. Show all
Med Hypotheses. 2008;71(1 ):85-90. Epub 2008 Apr 2.

Department of Biochemistry, University of
Wisconsin, Madison, 433 Babcock Drive, Madison,
WI 53706, USA. hayes@biochem. wisc.edu

Abstract
Multiple sclerosis (MS) is a neurodegenerative disease of uncertain etiology. In MS, neurodegeneration is thought to be secondary to
autoimmune-mediated damage. However, no cohesive explanation yet exists as to how environmental factors interact to induce a
neurodegenerative autoimmune response. Insufficient sunlight exposure and chronic viral infections have been proposed as unrelated
environmental risk factors for MS. We suggest that these risk factors may act synergistically to enable the pathogenic autoimmune response.
Low ultraviolet light (UVL) exposure depletes vitamin D3 stores, and low vitamin D3 levels correlate strongly with high MS risk. The central
nervous system converts vitamin D3 into 1,25 -dihydroxyvitamin D3 (1,25 -(OH)2 D3), a biologically active hormone with
anti-inflammatory and neuro-protective functions that depend on IL-10-producing regulatory lymphocytes. Herpesvirus infection also
correlates with MS risk. Some herpesviruses like Epstein-Barr virus produce an IL-10-like cytokine termed vIL-10.

We hypothesize that vIL-10 may induce a dysfunction of IL-10-producing regulatory lymphocytes, thereby undermining the protective
functions of sunlight, vitamin D3, and 1,25 -(OH)2D3. The vIL-10 could elicit a host immune response capable of neutralizing or depleting
IL-10, or the vIL-10 could compete with IL-10 but fail to perform an essential IL-10 function. In either case, the lack of sunlight exposure and
the herpes virus infection might synergize to induce a defect in IL-10-producing regulatory lymphocyte function that undermines self-tolerance
mechanisms and enables a pathogenic autoimmune response to neural proteins.
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