Serological and experimental studies in different forms of myasthenia gravis.

Abstract

Antibodies to the acetylcholine receptor (AChR) have been recognized for over 40 years and have been important in the diagnosis of myasthenia gravis (MG), and its recognition in patients of different ages and thymic pathologies. The 10-20% of patients who do not have AChR antibodies are now known to comprise different subgroups, the most commonly reported of which is patients with antibodies to muscle-specific kinase (MuSK). The use of cell-based assays has extended the repertoire of antibody tests to clustered AChRs, low-density lipoprotein receptor-related protein 4, and agrin. Autoantibodies against intracellular targets, namely cortactin, titin, and ryanodine receptor (the latter two being associated with the presence of thymoma), may also be helpful as biomarkers in some patients. IgG4 MuSK antibodies are clearly pathogenic, but the coexisting IgG1, IgG2, and IgG3 antibodies, collectively, have effects that question the dominance of IgG4 as the sole pathologic factor in MuSK MG. After a brief historical review, we define the different subgroups and summarize the antibody characteristics. Experiments to demonstrate the in vitro and in vivo pathogenic roles of MuSK antibodies are discussed.

• Authors: Angela Vincent, Saif Huda, Michelangelo Cao, Hakan Cetin, Inga Koneczny, Pedro M Rodriguez Cruz, Leslie Jacobson, Stuart Viegas, Saiju Jacob, Mark Woodhall, Akiko Nagaishi, Angelina Maniaol, Valentina Damato, M Isabel Leite, Judith Cossins, Richard Webster, Jacqueline Palace, David Beeson
• Journal: Annals of the New York Academy of Sciences (Ann N Y Acad Sci) Vol. 1413 Issue 1 Pg. 143-153 (02 2018) ISSN: 1749-6632 [Electronic] United States
• PMID: 29377162 (Publication Type: Journal Article, Review)
• Copyright: © 2018 New York Academy of Sciences.

Chemical References

• Agrin
• Autoantibodies
• Immunoglobulin G
• KCNA4 protein, human
• Kv1.4 Potassium Channel
• LDL-Receptor Related Proteins
• LRP4 protein, human
• Receptors, Cholinergic
• MUSK protein, human
• Receptor Protein-Tyrosine Kinases

Topics

• Agrin (immunology)
• Autoantibodies (immunology)
• Humans
• Immunoglobulin G (immunology)
• Kv1.4 Potassium Channel (immunology)
• LDL-Receptor Related Proteins (immunology)
• Myasthenia Gravis (classification, immunology)
• Receptor Protein-Tyrosine Kinases (immunology)
• Receptors, Cholinergic (immunology)