Wednesday, 25 September 2013

Neural Components as targets for autoimmuntity

Puentes F, van der Star BJ, Victor M, Kipp M, Beyer C, Peferoen-Baert R, Ummenthum K, Pryce G, Gerritsen W, Huizinga R, Reijerkerk A, van der Valk P, Baker D, Amor S.Characterization of immune response to neurofilament light in experimental autoimmune encephalomyelitis. J Neuroinflammation. 2013 Sep ;10(1):118. [Epub ahead of print]

BACKGROUND:
Autoimmunity to neuronal proteins occurs in several neurological syndromes, where cellular and humoral responses are directed to surface as well as intracellular antigens. Similar to myelin autoimmunity, pathogenic immune response to neuroaxonal components such as neurofilaments may contribute to neurodegeneration in multiple sclerosis.
METHODS:We studied the immune response to the axonal protein neurofilament light (NF-L) in the experimental autoimmune encephalomyelitis animal model of multiple sclerosis. To examine the association between T cells and axonal damage, pathology studies were performed on NF-L immunized mice. The interaction of T cells and axons was analyzed by confocal microscopy of central nervous system tissues and T-cell and antibody responses to immunodominant epitopes identified in ABH (H2-Ag7) and SJL/J (H2-As) mice. These epitopes, algorithm-predicted peptides and encephalitogenic motifs within NF-L were screened for encephalitogenicity.
RESULTS:Confocal microscopy revealed both CD4+ and CD8+ T cells alongside damaged axons in the lesions of NF-L immunized mice. CD4+ T cells dominated the areas of axonal injury in the dorsal column of spastic mice in which the expression of granzyme B and perforin was detected. Identified NF-L epitopes induced mild neurological signs similar to the observed with the NF-L protein, yet distinct from those characteristic of neurological disease induced with myelin oligodendrocyte glycoprotein.
CONCLUSIONS: Our data suggest that CD4+ T cells are associated with spasticity, axonal damage and neurodegeneration in NF-L immunized mice. In addition, defined T-cell epitopes in the NF-L protein might be involved in the pathogenesis of the disease.


More many years EAEologists soley focused on myelin as a potential target.This study shows that immune responses to nerve proteins can cause a disease that is comparable to that induced  myelin although grey matter lesions can occur and the clinical disease can be abit different. Is this relevant to MS well maybe we see that is often antibodies against neurofilament light in the tissues from MSers. Are these harmless well I am sorry to say no but that's another story. 
CoI This is work by Team G

4 comments:

  1. Mouse,

    Why couldn't this research have been done on humans?

    ReplyDelete
    Replies
    1. Good question for Dr Love.
      The simple answer is it has been done, but it is is not always easy to see if the response is disease causing or protective. The antibody response is the former. This is being used as a biomarker for MS trials and so it is important that we understand what it is doing in MS.

      Delete
  2. A MS-like disease EAE can be induced using NF-L protein instead of myelin proteins. If grey matter is targeted initially using NF-L will there be eventual myelin damage? Does myelin/adjuvant elicit more robust T-cell response than NF-L ?

    ReplyDelete
    Replies
    1. It depends on which myelin antigen some do very little but that dependson their immune genes

      Delete

Please note that all comments are moderated and any personal or marketing-related submissions will not be shown.