Trial reportProceedings of the National Academy of Sciences of the United States of America2013
MuSK IgG4 autoantibodies cause myasthenia gravis by inhibiting binding between MuSK and Lrp4.
Trial report in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
120 citing papers in PubMed, 2 syntheses or guidelines pooled it, 285 citations in OpenAlex.
- The efficacy and safety of efgartigimod for refractory myasthenia gravis: a systematic review and meta-analysis.European journal of medical research · 2025Pooled it
- The efficacy and safety of FcRn inhibitors in patients with myasthenia gravis: a systematic review and meta-analysis.Journal of neurology · 2024Pooled it
- IgG Subclass (IgG1-4) and IgA Autoantibody Profiles Against Muscle-Specific Kinase in a Greek Cohort.Muscle & nerve · 2026Article
- IgA autoantibodies demonstrate a novel mechanism of MuSK myasthenia gravis pathology.Brain : a journal of neurology · 2026Article
- Eyelid twitching in MuSK-myasthenia gravis.Acta neurologica Belgica · 2026Article
- Monoclonal antibody passive experimental autoimmune myasthenia gravis: current progress and future directions.Cell & bioscience · 2026Review
- B Cell Subsets and Atherosclerosis: Updates and Emerging Concepts.Immunological reviews · 2026Review
- Clinical utility of human leukocyte antigen genotyping and immunoglobulin G4 autoantibody testing in autoimmune neurological diseases: A focused minireview.World journal of biological chemistry · 2026Review
- Myasthenia gravis: from recognition of heterogeneity to a paradigm shift toward precision therapy.Frontiers in immunology · 2026Review
- MuSK myasthenia gravis: from antigen-antibody to clinical translation.Frontiers in immunology · 2026Review
- Dysbiosis of gut microbiota and metabolomic alterations in myasthenia gravis: insights from 16S rRNA sequencing and untargeted metabolomics.Frontiers in immunology · 2026Article
- The Neuromuscular Junction: A Shared Vulnerability in Aging and Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Review
- MuSK cysteine-rich domain antibodies are pathogenic in a mouse model of autoimmune myasthenia gravis.The Journal of clinical investigation · 2025Article
- Targeting the Neonatal Fc Receptor in Autoimmune Diseases: Pipeline and Progress.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025Review
- Patient-specific therapeutic benefit of MuSK agonist antibody ARGX-119 in MuSK myasthenia gravis passive transfer models.iScience · 2025Article
- Complement activation in immunological neurological disorders: mechanisms and therapeutic strategies.Frontiers in neurology · 2025Review
- A pilot study of the immunological profile and efficacy of rituximab in muscle-specific kinase antibody-positive myasthenia gravis.Frontiers in immunology · 2025Article
- Efgartigimod for induction and maintenance therapy in muscle-specific kinase myasthenia gravis.Therapeutic advances in neurological disorders · 2025Article
- Agonist antibody to MuSK protects mice from MuSK myasthenia gravis.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- IgLON5-IgG: Innocent Bystander or Perpetrator?International journal of molecular sciences · 2024Review
60 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
Myasthenia gravis (MG) is a severely debilitating autoimmune disease that is due to a decrease in the efficiency of synaptic transmission at neuromuscular synapses. MG is caused by antibodies against postsynaptic proteins, including (i) acetylcholine receptors, the neurotransmitter receptor, (ii) muscle-specific kinase (MuSK), a receptor tyrosine kinase essential for the formation and maintenance of neuromuscular synapses, and (iii) low-density lipoprotein receptor-related protein 4 (Lrp4), which responds to neural Agrin by binding and stimulating MuSK. Passive transfer studies in mice have shown that IgG4 antibodies from MuSK MG patients cause disease without requiring complement or other immune components, suggesting that these MuSK antibodies cause disease by directly interfering with MuSK function. Here we show that pathogenic IgG4 antibodies to MuSK bind to a structural epitope in the first Ig-like domain of MuSK, prevent binding between MuSK and Lrp4, and inhibit Agrin-stimulated MuSK phosphorylation. In contrast, these IgG4 antibodies have no direct effect on MuSK dimerization or MuSK internalization. These results provide insight into the unique pathogenesis of MuSK MG and provide clues toward development of specific treatment options.
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Registered trials
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.