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

voner

Senior Member
Messages
592
here is a summary:

http://loonylabs.org/2015/10/10/blood-clotting-protein-immune-attack-on-the-brain/


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:

http://www.nature.com/ncomms/2015/150910/ncomms9164/full/ncomms9164.html


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:

Marco

Grrrrrrr!
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Location
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.