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

• Published in: Journal of internal medicine Vol. 275; no. 1; pp. 12 - 26
• Main Authors: Huijbers, M. G., Lipka, A. F., Plomp, J. J., Niks, E. H., Maarel, S. M., Verschuuren, J. J.
• Format: Journal Article
• Language: English
• Published: England 01.01.2014
• Subjects: acetylcholine receptor; Antigen-Antibody Reactions; Autoantibodies - metabolism; Autoimmunity; epitope mapping; Epitope Mapping - methods; Epitope Mapping - trends; Epitopes - metabolism; Humans; Immunoglobulin G - classification; Immunoglobulin G - immunology; muscle‐specific kinase; myasthenia gravis; Myasthenia Gravis - immunology; Myasthenia Gravis, Autoimmune, Experimental - drug therapy; neuromuscular junction; Neuromuscular Junction - immunology; Receptors, Cholinergic - immunology; Therapies, Investigational - methods; Therapies, Investigational - trends; myasthenia gravis; acetylcholine receptor; autoimmunity; muscle-specific kinase; neuromuscular junction; epitope mapping
• ISSN: 0954-6820; 1365-2796
• DOI: 10.1111/joim.12163

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.