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Humoral autoimmunity in multiple sclerosis

  • Edgar Meinl
    Correspondence
    Corresponding author. Institute of Clinical Neuroimmunology, Ludwig-Maximilians-University, Marchioninistr. 15, 81377 Munich, Germany. Tel.: +49 89 8578 3519; fax: +49 89 89950163.
    Affiliations
    Department of Neuroimmunology, Max Planck Institute of Neurobiology, Am Klopferspitz 18, 82152 Martinsried, Germany

    Institute of Clinical Neuroimmunology, Ludwig Maximilians University, Marchioninistr. 15, 81377 Munich, Germany
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  • Tobias Derfuss
    Affiliations
    Department of Neuroimmunology, Max Planck Institute of Neurobiology, Am Klopferspitz 18, 82152 Martinsried, Germany

    Institute of Clinical Neuroimmunology, Ludwig Maximilians University, Marchioninistr. 15, 81377 Munich, Germany

    Neurology, University of Erlangen-Nürnberg, Germany
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  • Markus Krumbholz
    Affiliations
    Department of Neuroimmunology, Max Planck Institute of Neurobiology, Am Klopferspitz 18, 82152 Martinsried, Germany

    Institute of Clinical Neuroimmunology, Ludwig Maximilians University, Marchioninistr. 15, 81377 Munich, Germany
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  • Anne-Katrin Pröbstel
    Affiliations
    Department of Neuroimmunology, Max Planck Institute of Neurobiology, Am Klopferspitz 18, 82152 Martinsried, Germany

    Institute of Clinical Neuroimmunology, Ludwig Maximilians University, Marchioninistr. 15, 81377 Munich, Germany
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  • Reinhard Hohlfeld
    Affiliations
    Department of Neuroimmunology, Max Planck Institute of Neurobiology, Am Klopferspitz 18, 82152 Martinsried, Germany

    Institute of Clinical Neuroimmunology, Ludwig Maximilians University, Marchioninistr. 15, 81377 Munich, Germany
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Published:September 06, 2010DOI:https://doi.org/10.1016/j.jns.2010.08.009

      Abstract

      The important role of B cells and autoantibodies in the pathogenesis of MS is increasingly appreciated. The recruitment and maintenance of B cells and plasma cells in MS lesions is presumably based on local production of lymphoid chemokines and B cell activation factor of the TNF family (BAFF). The failure of the clinical trial with Atacicept targeting BAFF and its relative APRIL was a great surprise and cannot readily be explained. A role for BAFF in CNS physiology, e.g. via targeting of the Nogo-66 receptor might have to be considered. The identification of patient subgroups based on autoantibodies is a future challenge. Currently patients with neuromyelitis optica (NMO) can be identified by antibodies to aquaporin 4 and about a third of children with acquired demyelinating diseases have antibodies against conformationally correct MOG, while such antibodies are hardly found in adult MS patients. Searching for new targets of the autoimmune response in adult MS patients, we have identified two axo-glial proteins focused around the node of Ranvier, namely neurofascin and contactin-2/TAG-1. Testing the functional relevance of such an autoimmune response in animal models revealed that antibodies to neurofascin may induce axonal injury and that T cells specific for contactin-2/TAG-1 mediate preferentially gray matter injury.

      Keywords

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