title: Pathogenic IgG4 subclass autoantibodies in MuSK myasthenia gravis.
abstract: Autoantibodies against muscle-specific kinase (MuSK), a protein essential for clustering of acetylcholine receptors at the neuromuscular junction (NMJ), are detected in the serum of a proportion of myasthenia gravis (MG) patients. In most MuSK MG patients the anti-MuSK activity resides in the IgG4 subclass, a minor IgG component without very well-defined, but presumably anti-inflammatory, roles in immunity. In recent years, several animal model studies showed that anti-MuSK autoantibodies can cause muscle weakness by directly affecting NMJ function and, therefore, are likely not simply bystander disease markers in MuSK MG patients. In passive transfer mice, we recently provided proof that MuSK MG patient IgG4 is severely myasthenogenic, causing functional defects at NMJs. Against the clinical, serological, and pharmacological background of MuSK MG, here we discuss the MuSK MG animal models generated by our laboratory and others that have been instrumental in elucidating the etiological and pathophysiological roles of anti-MuSK antibodies.
authors.affiliation: Department of Neurology, Medical Genetics Center, Leiden University Medical Center, Leiden, the Netherlands. j.j.plomp@lumc.nl
authors.forename: Jaap J
authors.initials: JJ
authors.lastname: Plomp
authors.forename: Maartje G
authors.initials: MG
authors.lastname: Huijbers
authors.forename: Silvère M
authors.initials: SM
authors.lastname: van der Maarel
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Verschuuren
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000097:blood*; D004195:Disease Models, Animal; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D051379:Mice; D009157:Myasthenia Gravis / Q000276:immunology* / Q000503:physiopathology; D020794:Receptor Protein-Tyrosine Kinases / Q000276:immunology*; D011950:Receptors, Cholinergic / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D011950:Receptors, Cholinergic; C095714:MUSK protein, human; D020794:Receptor Protein-Tyrosine Kinases