Research:Pathogenic Antibodies, Autoimmunity in MS

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Pathological and clinical studies implicate antibody-dependent mechanisms in the immunopathogenesis of multiple sclerosis.
We tested this hypothesis directly by investigating the ability of
patient-derived immunoglobulins to mediate demyelination and axonal
injury in vitro. Using a myelinating culture system, we developed a
sensitive and reproducible bioassay to detect and quantify these effects
and applied this to investigate the pathogenic potential of
immunoglobulin G preparations obtained from people with
multiple sclerosis
(n = 37), other neurological diseases (n = 10) and healthy control
donors (n = 13). This identified complement-dependent demyelinating
immunoglobulin G responses in approximately 30% of patients with
multiple sclerosis,
which in two cases was accompanied by significant complement-dependent
antibody mediated axonal loss. No pathogenic immunoglobulin G responses
were detected in people with other neurological disease or healthy
controls, indicating that the presence of these demyelinating/axopathic
autoantibodies is specific for a subset of people with
multiple sclerosis.
Immunofluorescence microscopy revealed immunoglobulin G preparations
with demyelinating activity contained antibodies that specifically
decorated the surface of myelinating oligodendrocytes and their
contiguous myelin sheaths. No other binding was observed indicating that
the response is restricted to autoantigens expressed by terminally
differentiated myelinating oligodendrocytes. In conclusion, our study
identifies axopathic and/or demyelinating autoantibody responses in a
subset of patients with
multiple sclerosis. This observation underlines the mechanistic heterogeneity of multiple sclerosis and provides a rational explanation why some patients benefit from antibody depleting treatments.
Green (myelin) Red (Axons) on Right Noode of Ranvier proteins suchas caspr (blue) and in II sodium channels in green also.
If you remember we were recently taking about lesion heterogeneity in MS and some lesions had evidence of antibody binding and complement activation. This combination is a way of damaging and killing the target cell. 
There has been much tooing and frowing about whether there is any autoimmunity occuring in MS and we have said that we know that there are undesirable antibodies in the blood because they can cause symptoms when delivered to the brains of animals, this is yet further example of this. 
The authors have developed a myelinating culture system whereby they have rat nerves and myelinated them in cell culture. They have added antibodies from  the blood of people with MS and about 30% of them had demyelinating antibody. This means that 70% didn’t which can mean there is heterogeneity and a different mechanism between MSers. 
It could be that there are different levels in the blood dependent on disease activity and could vary over time, although this was not revent in the samples they tested, as we know MRI activity varies, or there are more antibodies in the CNS compared the blood. Alternatively the antibodies may not react with rat proteins used in the asssay, although this is less likely as there is conservation of many myelin proteins. 

The target was not only myelin proteins such as myelin oligodendrocyte glycoprotein as some killng antibodies were directed to nerve proteins such as neurofascin-186 that is present at the Nodes of Ranvier. 

Whilst this does not say that MS is an autoimmune disease, it clearly show that B cell autoimmunity can be pathogenic . It may suggest that only a subset of MSers would respond B cell inhibitory therapy. They they also showed that plasma exchange could remove the myelin damaging antibodies. This study clearly shows that some form of autoimmunity exsists in at least some MSers

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MouseDoctor

6 comments

  • Deleted post by Andy by Mistake

    Andy Clarke has left a new comment on your post "Research:Pathogenic Antibodies, Autoimmunity in MS…":

    Hi all,
    Read with interest the paper above, I've been trying attach another study re Autonomic dysfunction: A unifying MS theory, linking CCSVI, vitamin D3, and Epstein-Barr virus.
    If you can take a look I would appreciate your thoughts.

    Regards Andy Clarke
    (name and address available)

  • Hi Mouse Doctor2, thanks for elucidating I'm sure my wheelchair dependent, and today confined to bed Wife will be most appreciative and encouraged.
    If any one could be less callous I would still appreciate your thoughts.

    Regards Andy Clarke

  • Dear Andy
    I am sorry to hear your news about your wife, send her my regards.

    Maybe you can watch the video today about the nervous system so that you are familiarize yourself about the nervous and autonomic nervous system.

    In brief the paper by Sternberg is trying to link CCSVI, virus and sunlight and immunity together.

    If you accept that CCSVI is an entity, which many people don't, my take is that this idea says that CCSVI is not the cause, but a consequence of MS

    The autonomic nervous system which controls involuntary actions, like breathing, can innervate both the immune glands and also the blood vessels so it can control blood pressure. This can be through control by affecting muscles in arteries and on the heart etc.

    Because of damage to signalling within the autonomic nervous system, it is suggested that there can be relaxation of vessels and that they collapse and restrict blood flow and this can lead to obstruction of the vein. There can also be collapse of the vessels in veins also because of autonomic nervous activity so you have CCSVI.

    Inflammation leads to part of the autonomic defects and can affect the blood vessels. The author then says that the autonomic nerve system can affect the immune system and that virus can affect the autonomic nerve system.

    Therefore this paper is not much for treating CCSVI as the condition will come straight back. It affects arteries and reflux and back jets are not mentioned so I am surprised VV has not been to post on this idea.

    As ever this is another example of armchair science, which as you know is not my favourite type of science.

    This area is not my field so please accept my apologies if it is not quite spot-on or sufficiently described. There is information about how the arteries may collapse but I'm sure there will be people saying it is all veins

  • Dear Andy,
    I am sorry to hear about your wife and don't wish to appear callous and I'm sorry if I have offended you. We're just trying to filter the good and bad stuff that gets published and give an opinion on itas we see it. We may not be right all the time but they are honest opinions. As MouseDoctor says this is armchair speculation based on a very dubious premise (in the case of CCSVI) with no personal research by the author to back it up. The evidence for Vitamin D and EBV in MS is much more robust.

By MouseDoctor

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