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drop of blood in the brain activates an autoimmune response akin to multiple sclerosis

Discussion in 'Other Health News and Research' started by voner, Oct 13, 2015.

  1. voner

    voner Senior Member

    here is a summary:

    some quotes from the article:

    In the current study, the scientists created a new animal model of disease to determine if BBB leakage can cause autoimmunity. They discovered that injecting just one drop of blood into the brain set off the brain’s immune response, kick-starting a chain reaction that resulted in inflammation and myelin damage. Myelin is the protective sheath that insulates nerve fibers in the brain, and it is the primary site of injury in MS. What’s more, the scientists were able to pinpoint a specific protein in the blood, the blood-clotting factor fibrinogen, as the trigger for the disease-causing process.........

    ......“These findings question a long-held paradigm that myelin-specific T cells initiate inflammation in the brain through activation of microglia and brain macrophages,” says Scott Zamvil, MD, PhD, a professor of neurology at the University of California, San Francisco and co-author on the paper.

    “This study demonstrates that the original paradigm may also occur in reverse. Namely, initial activation of microglia and brain macrophages may activate T cells.”......

    so from what I read they think that fibriogen (from the blood) is deposited as fibrin, which triggers an neuroinflammation cascade and seems to induce an autoimmune response.... I think it's very interesting that the findings cast doubt on the belief that T cells initiate the autoimmune response.

    it is a open access paper – here it is:

    here is the abstract( my bold emphasis added):

    Autoimmunity and macrophage recruitment into the central nervous system (CNS) are cri-

    tical determinants of neuroinflammatory diseases. However, the mechanisms that drive

    immunological responses targeted to the CNS remain largely unknown. Here we show that

    fibrinogen, a central blood coagulation protein deposited in the CNS after blood–brain barrier

    disruption, induces encephalitogenic adaptive immune responses and peripheral macrophage

    recruitment into the CNS leading to demyelination. Fibrinogen stimulates a unique tran-

    scriptional signature in CD11b þ antigen-presenting cells inducing the recruitment and local

    CNS activation of myelin antigen-specific Th1 cells. Fibrinogen depletion reduces Th1

    cells in the multiple sclerosis model, experimental autoimmune encephalomyelitis. Major

    histocompatibility complex (MHC) II-dependent antigen presentation, CXCL10- and CCL2-

    mediated recruitment of T cells and macrophages, respectively, are required for fibrinogen-

    induced encephalomyelitis. Inhibition of the fibrinogen receptor CD11b/CD18 protects from

    all immune and neuropathologic effects. Our results show that the final product of the

    coagulation cascade is a key determinant of CNS autoimmunity.

    Comments anyone? @Marco @Jonathan Edwards

    Last edited: Oct 15, 2015
  2. Marco

    Marco Grrrrrrr!

    Near Cognac, France
    I'm no expert (understatement) and I've yet to read the full paper but I don't see why this model differs from a localised bleed in the brain which you would expect to activate microglia as the brain's immune 'first responders' which then recruit other immune cells including T cells. I'm pretty sure that fibrinogen/fibrin is one of many DAMPs that activates microglia via TLR's. How this then leads to an autoimmune disease I'm sure they've explained?

    But presumably the idea that T cells 'must' initiate an inflammatory cascade derives from models of T cell mediated autoimmunity in MS? Apparently there are forms of MS where these lesions are primarily hypoxic without demyelination where there is very little T cell infiltration found in tissues and where microglial activation is proposed as playing the key role.

    Hard to say how this might relate to ME/CFS.
    voner likes this.
  3. Marco

    Marco Grrrrrrr!

    Near Cognac, France

    I spotted the thread but didn't receive a tag notification for some reason - just to let you know.

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