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Auto-Immune Disease: The Viral Route Is Confirmed

Discussion in 'Other Health News and Research' started by Overstressed, Dec 23, 2012.

  1. Overstressed

    Overstressed Senior Member

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    Dec. 19, 2012 — Why would our immune system turn against our own cells?

    This is the question that the combined Inserm/CNRS/ Pierre and Marie Curie University/Association Institut de Myologie have strived to answer in their "Therapies for diseases of striated muscle," concentrating in particular on the auto-immune disease known as myasthenia gravis. Through the project known as FIGHT-MG (Fight Myasthenia Gravis), financed by the European Commission and coordinated by Inserm, Sonia Berrih-Aknin and Rozen Le Panse have contributed proof of the concept that a molecule imitating a virus may trigger an inappropriate immune response, causing muscular function to deteriorate.

    These results have been published in Annals of Neurology, accessible on line.

    Myasthenia, a rare auto-immune disease

    Myasthenia gravis is a rare auto-immune disease (5,000 to 6,000 patients in France) that produces muscular weakness and exhaustion. It generally affects the facial muscles first, and may then become generalised through the muscles of the limbs or the respiratory muscles, causing respiratory distress.

    This is due to the production of circulating auto-antibodies that block the acetylcholine receptors (RACh), these neurotransmitters being necessary for transmitting the motor nerve signal to the neuro-muscular junction.
    Could a viral infection be the origin of myasthenia?
    Myasthenia is a multi-factorial disease in which environmental factors seem to play a key triggering role. Viral infections are suspected but it is hard to prove the role of a virus in triggering the condition. In fact, diagnosis of myasthenia is often made months, or even years, after the actual start of the illness when the virus is no longer detectable, even though the signature left by the virus is visible long after the infection.
    Proof of the concept of a viral origin contributed by researchers
    Under the European FIGHT-MG project, the team of researchers managed to decode the trigger for the illness by using a molecule that mimics the RNA double viral strand (Poly(I:C)).
    To do this, they concentrated on the organ that plays a central role in the disease -- the thymus. It is in this gland located in the thorax that the T-lymphocytes mature, these being the key players in immune response that are normally programmed to avoid the development of any auto-immunity.
    The researchers were thus able to show in vitro that the Poly(I:C) was capable of specifically inducing an over-expression of RACh through thymal epithelial cells, while activating three proteins (the "toll-like" receptor 3 (TLR3), the protein kinase R (PKR) and interferon-beta (IFN-â)); it is this last that produces inflammation in the thymus.
    At the same time, they analysed pathological thymus glands of myasthenia sufferers in whom they observed over-expression of these same three proteins in the immune system, characteristic of a viral infection.
    Finally, the researchers also managed to identify the same molecular changes in the thymus glands of mice, after they had been injected with Poly(I:C). After a prolonged injection period, they also observed a proliferation in the mice of B anti-RACh cells, the presence of auto-antibodies blocking the RACh receptors and clinical signs synonymous with the muscular weakness found in myasthenia. These original results show that molecules that mimic a viral infection are capable of inducing myasthenia in the mouse, something that had never been demonstrated before.
    This set of papers published in the Annals of Neurology provides proof of the concept that a viral infection can cause inflammation of the thymus and lead to the development of auto-immune myasthenia.
    The next stages of the research will consist in determining which exogenous virus this may be or whether it is a case of the abnormal activation of an anti-viral response by endogenous molecules.
    FIGHT-MG (Fighting Myasthenia Gravis) -- a European collaboration making giant leaps forward
    The FIGHT-MG project seeks to determine the genetic and environmental risk factors associated with the occurrence of the illness and its development. The project aims also to identify the key immunological molecules associated with its appearance, and to study the pathogenic mechanisms at the neuromuscular junction, establish new diagnostic tests, as well as new treatments (cellular treatments, immuno-regulatory treatments, immuno-absorption of pathogenic auto-antibodies and other pharmacological treatments).
    "When one is working on a rare disease, it is essential to work through networking, so as to be able to share our facilities and resources to promote fundamental and clinical research. It is also crucial to communicate permanently with patient associations. It is this combination that enables us to take giant steps in the treatment of rare conditions," explains Sonia Berrih-Aknin.


    Personal note: This could be groundbreaking for all other 'autoimmune' diseases, especially when they find a/the virus!


    The link to the article: http://www.sciencedaily.com/releases/2012/12/121219133555.htm

    The reference to the paper:

    Journal Reference:
    Perrine Cufi, Nadine Dragin, Julia Miriam Weiss, Pilar Martinez-Martinez, Marc H. De Baets, Régine Roussin, Elie Fadel, Sonia Berrih-Aknin, Rozen Le Panse. Implication of dsRNA signaling in the etiology of autoimmune myasthenia gravis. Annals of Neurology, 2012; DOI: 10.1002/ana.23791

    Link to the research paper:

    http://onlinelibrary.wiley.com/doi/...ionid=29FDB09DAB9878CEB04F858AE70FFB53.d01t02

    Best wishes,
    OS.
     
  2. beaker

    beaker ME/cfs 1986

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    brain too shot to much more then skim. what caught my eye. Poly I: C is generic Ampligen. ( ok they may tweak it a bit in the formulation they give. )
    Anyone who has a working brain want to take a shot at what that would mean for ME/CFS ?
     
  3. Sing

    Sing Senior Member

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    I have had occasion to think of myasthenia gravis lately as one of the pills the autonomic specialist is trying me on is Mestinon (pyridogstimine) which is used for myasthenia gravis. It helps with nerve conduction in the sympathetic nervous system with the part of it which uses nicotinic receptors. (Aristotle Onassis, who married Jacqueline Kennedy, died of it--First time I had heard of it.) I have serious difficulties with Orthostatic Hypotension. Also have small fiber neuropathy and increasing motor incoordination, "dystaxias", etc. I suspect some connective tissue disease is involved too as blood vessels sometimes break spontaneously--not varicose veins. I don't know what is causing what, but believe that there is an autoimmune process underway now, though my intial problems were kicked off with viral infections. I don't believe I have mysasthenia gravis, per se, but some of the symptoms are the same as my ME/CFS develops and impairs my nervous system.

    My neurologist who specializes in autonomic dysfunction is approaching my OI in terms of treatment and trying to see what is going on, but can only hypothesize, I think, about cause. We here can speculate about causes and I hope they will be researched so that this process of degeneration could be treated more at its point of origin than at its consequences. But, of course, I am mainly concerned about treatment.
     
  4. lansbergen

    lansbergen Senior Member

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    If ampligen increases a7nAchR numbers on the nerves vagus and immunecellls there might be more not occupied by antibodies receptors available acetylcholine can bind to. That could explain why it helps.

    My immunemodulator improves achetylcholine effect on a7 nAchR.
     
  5. Sushi

    Sushi Moderator and Senior Member Albuquerque

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    How is the Mestinon going? I know several people who have taken it and my impression is that it is very helpful for some, but doesn't make a lot of difference for most. Again, it would be helpful to understand what treatments help what subsets (and it even identify the subsets!).

    Sushi
     
    merylg and SOC like this.
  6. SickOfSickness

    SickOfSickness Senior Member

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    Most of what you said applies to me too. All of this:

    It was really good for me, but the side effects were hard on me. And it didn't work half of the time for me, on my bad days.
     
  7. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    In what ways did mestinon help?
    I have heard mestinon can improve sleep and growth hormone release??
     
  8. Sing

    Sing Senior Member

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    When this autonomic specialist inches me higher off the bottom rung of Mestinon, I will let you know what value and side effects it has on me. Right now, at the lowest dose, I have some slight impressions about what it is doing, but don't want to mislead anyone with a premature judgment.
     

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