Pathogenic immune mechanisms at the neuromuscular synapse: the role of specific antibody-binding epitopes in myasthenia gravis

Authors

  • M. G. Huijbers,

    Corresponding author
    1. Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands
    2. Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands
    • Correspondence: Maartje G. Huijbers, Departments of Human Genetics and Neurology, Leiden University Medical Center, Research Building, S3-05, P.O. Box 9600, 2300 RC Leiden, the Netherlands.

      (fax: +31 (0)71 526 8285; e-mail: M.G.M.Huijbers@lumc.nl).

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  • A. F. Lipka,

    1. Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands
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  • J. J. Plomp,

    1. Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands
    2. Department of Molecular Cell Biology-Neurophysiology, Leiden University Medical Center, Leiden, the Netherlands
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  • E. H. Niks,

    1. Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands
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  • S. M. van der Maarel,

    1. Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands
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  • J. J. Verschuuren

    1. Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands
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Abstract

Autoantibodies against three different postsynaptic antigens and one presynaptic antigen at the neuromuscular junction are known to cause myasthenic syndromes. The mechanisms by which these antibodies cause muscle weakness vary from antigenic modulation and complement-mediated membrane damage to inhibition of endogenous ligand binding and blocking of essential protein–protein interactions. These mechanisms are related to the autoantibody titre, specific epitopes on the target proteins and IgG autoantibody subclass. We here review the role of specific autoantibody-binding epitopes in myasthenia gravis, their possible relevance to the pathophysiology of the disease and potential implications of epitope mapping knowledge for new therapeutic strategies.

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