Sunday, 13 December 2015

Human EAE and MS are similar

Höftberger R, Leisser M, Bauer J, Lassmann H.Autoimmune encephalitis in humans: how closely does it reflect multiple sclerosis ? Acta Neuropathol Commun. 2015;3(1):80. doi: 10.1186/s40478-015-0260-9.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. Immunological studies suggest that it is a T-cell mediated autoimmune disease, although an MS-specific target antigen for autoimmunity has so far not been identified. Models of experimental autoimmune encephalomyelitis in part reproduce features of MS, but none of the models so far covers the entire spectrum of pathology and immunology. Autoimmune disease of the nervous system has occasionally been observed in humans after active sensitization with brain tissue or brain cells, giving rise to acute demyelinating polyradiculoneuritis, acute disseminated encephalomyelitis and in rare cases reflecting an inflammatory demyelinating condition similar to acute multiple sclerosis. In this study we analyzed in detail the immunopathology in archival autopsy tissue of a patient who died with an MS like disease after repeated exposure to subcutaneous injections of lyophilized brain cells.
RESULTS: The pathology of this patient fulfilled all pathological diagnostic criteria of MS. Demyelination and tissue injury was associated with antibody (IgM) deposition at active lesion sites and complement activation. Major differences to classical EAE models were seen in the composition of inflammatory infiltrates, being dominated by B-cells, infiltration of IgM positive plasma cells, profound infiltration of the tissue by CD8(+) T-lymphocytes and a nearly complete absence of CD4(+) T-cells.
CONCLUSIONS: Our study shows that auto-sensitization of humans with brain tissue can induce a disease, which closely reflects the pathology of MS, but that the mechanisms leading to demyelination and tissue injury differ from those, generally implicated in the pathophysiology of MS through studies in experimental autoimmune encephalomyelitis

So human EAE is like MS, so all the more reason to study animal EAE....... yeah. There are B cell infiltrates and CD8 cells and near absence of CD4. 

You can get this in EAE but you start with a CD4 rich infiltrate and with time the T cell infiltrates burn away. You can get B cell rich cuffs etc full of CD8 too, we showed this when we transplanted IL-10 producing cells into the brains of mice with EAE.  However this report highlights the differences of mouse EAE and human MS.

However, are the pathologists comparing apples and pears, EAE taking a copy to a few weeks verses this patient that had been developing neurological symptoms for 4 years. This case was apparently reported in 1958 and they were treated with brain cells and placental cells for a year and half....and after the seventh injection they got signs. I guess the first question is what were they thinking when giving brain and placenta..may be DrK can read the original text (in German) to give us some logic.  However some people are currently injecting myelin proteins into the skin of people with MS. Will disaster occur too?

Of course there are differences between EAE in animals and that in humans but the point is that sensitization to brain material can induce a condition that has similarities with MS, therefore maybe MS has an autoimmune cause.


  1. I just don't understand why the overreaction of the immune system the placental cells in people with MS? And studies on the use of placental mesenchymal cells in progress?

  2. in mesenchymal stems they thing there are stem cells and that is why they are being used, however in 1958 i have no clue of the logic.

  3. What is the mechanism behind EAE? It seems that most of the research community believes that a virus targets the immune system, is it true? What are the evidence for the immune system causing the inflammation? (a cut provokes an inflammation, but the immune system comes only as a consequence not a cause).

    What if the virus targets mainly the nervous system. The virus would make the nervous cells produce an antigen driving the immune response. This could be a clever way to spread and infect other cells without the virus having to kill the cell to get out (immune system is here for that). What are your arguments against this proposal?

    1. The mechanism behind EAE is peripheral autoimmunity directed against the CNS. In MS they have looked for virus and have not found a consistent one

    2. I guess my question is: "what is the origin of the autoimmunity?".

    3. In EAE......the origin is usually MD2 :-)

    4. There is a viral model of MS in mice using Theiler's virus.


  4. XoR Xor have not posted your question as it shows links
    Exp Neurol. 2014 Nov;261:620-32. doi: 10.1016/j.expneurol.2014.07.020. Epub 2014 Aug 8.
    Progressive multiple sclerosis cerebrospinal fluid induces inflammatory demyelination, axonal loss, and astrogliosis in mice.
    Cristofanilli M1, Rosenthal H1, Cymring B1, Gratch D1, Pagano B1, Xie B1, Sadiq SA2.

    This shows there are products in csf that cause damage , in some cases these are definately antibodies

  5. From the paper "In short a 51-year-old male patient presented with a mild slowly progressive hemi-Parkinson syndrome, starting 4 years before his death. Due to the lack of other therapeutic options the patient was treated over a period of 17 months with 7 injections of lyophilized calf brain cells (derived from cortex, thalamus, hypothalamus, and striatum) and placenta cells (0.02 g dry weight in 6 to 8 ml of physiological saline) at two to four month intervals. The first 6 injections were well tolerated. Twenty two days after the seventh injection the patient developed progressive right-sided hemiparesis. This was followed by rapid deterioration of the neurological status, leading to paraparesis, spasticity of the lower extremities, positive Babinski reflex, and tremor, and finally progressed to a comatous state."

    Another warning of the potential harm of quack therapies folks!!

    1. Pretty damn interesting. I wonder what possessed them to treat this specific patient with such an odd "therapy"? I must admit I kind of like their creativity. It is likely that injections with stem cells of various types will form part of the treatment for MS one day.


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