ArticleThe Journal of physiology2010
Patient autoantibodies deplete postsynaptic muscle-specific kinase leading to disassembly of the ACh receptor scaffold and myasthenia gravis in mice.
Article in The Journal of physiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 93 citations in OpenAlex.
- Clinical effectiveness of efgartigimod in a broad population of patients with generalized myasthenia gravis: subgroup analyses from a randomized, double‑blind, placebo‑controlled, phase 3 trial (ADAPT).Journal of neurology · 2026Trial
- MuSK IgG4 autoantibodies cause myasthenia gravis by inhibiting binding between MuSK and Lrp4.Proceedings of the National Academy of Sciences of the United States of America · 2013Trial
- Muscle-Specific Kinase Signaling and Its Therapeutic Potential.Muscle & nerve · 2026Review
- MuSK myasthenia gravis: from antigen-antibody to clinical translation.Frontiers in immunology · 2026Review
- Myasthenia Gravis: Novel Findings and Perspectives on Traditional to Regenerative Therapeutic Interventions.Aging and disease · 2023Article
- IgG4 Antibodies Induced by Repeated Vaccination May Generate Immune Tolerance to the SARS-CoV-2 Spike Protein.Vaccines · 2023Review
- FcRN receptor antagonists in the management of myasthenia gravis.Frontiers in neurology · 2023Review
- Immunotherapies in MuSK-positive Myasthenia Gravis; an IgG4 antibody-mediated disease.Frontiers in immunology · 2023Review
- Structure and Function of the Mammalian Neuromuscular Junction.Comprehensive Physiology · 2022Article
- Is paravertebral muscles edema a consequence of neurogenic changes in MuSK-positive myasthenia gravis?Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology · 2022Article
- Muscle-Specific Kinase Myasthenia Gravis.Frontiers in immunology · 2020Review
- Myasthenia Gravis With Antibodies Against Muscle Specific Kinase: An Update on Clinical Features, Pathophysiology and Treatment.Frontiers in molecular neuroscience · 2020Review
- Review
- MuSK myasthenia gravis monoclonal antibodies: Valency dictates pathogenicity.Neurology(R) neuroimmunology & neuroinflammation · 2019Article
- Cannabinoid-induced increase of quantal size and enhanced neuromuscular transmission.Scientific reports · 2018Article
- IgG4-mediated autoimmune diseases: a niche of antibody-mediated disorders.Annals of the New York Academy of Sciences · 2018Review
- A New Classification System for IgG4 Autoantibodies.Frontiers in immunology · 2018Review
- Pathogenesis of myasthenia gravis: update on disease types, models, and mechanisms.F1000Research · 2016Review
- Animal models of myasthenia gravis: utility and limitations.International journal of general medicine · 2016Review
- Forced expression of muscle specific kinase slows postsynaptic acetylcholine receptor loss in a mouse model of MuSK myasthenia gravis.Physiological reports · 2015Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The postsynaptic muscle-specific kinase (MuSK) coordinates formation of the neuromuscular junction (NMJ) during embryonic development. Here we have studied the effects of MuSK autoantibodies upon the NMJ in adult mice. Daily injections of IgG from four MuSK autoantibody-positive myasthenia gravis patients (MuSK IgG; 45 mg day(1)i.p. for 14 days) caused reductions in postsynaptic ACh receptor (AChR) packing as assessed by fluorescence resonance energy transfer (FRET). IgG from the patients with the highest titres of MuSK autoantibodies caused large (51-73%) reductions in postsynaptic MuSK staining (cf. control mice; P < 0.01) and muscle weakness. Among mice injected for 14 days with control and MuSK patient IgGs, the residual level of MuSK correlated with the degree of impairment of postsynaptic AChR packing. However, the loss of postsynaptic MuSK preceded this impairment of postsynaptic AChR. When added to cultured C2 muscle cells the MuSK autoantibodies caused tyrosine phosphorylation of MuSK and the AChR beta-subunit, and internalization of MuSK from the plasma membrane. The results suggest a pathogenic mechanism in which MuSK autoantibodies rapidly deplete MuSK from the postsynaptic membrane leading to progressive dispersal of postsynaptic AChRs. Moreover, maintenance of postsynaptic AChR packing at the adult NMJ would appear to depend upon physical engagement of MuSK with the AChR scaffold, notwithstanding activation of the MuSK-rapsyn system of AChR clustering.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.