ArticleThe Journal of clinical investigation2013
Antibodies against low-density lipoprotein receptor-related protein 4 induce myasthenia gravis.
Article in The Journal of clinical investigation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.
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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.
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Who cites it
99 citing papers in PubMed, 210 citations in OpenAlex.
- Randomized study of adjunctive belimumab in participants with generalized myasthenia gravis.Neurology · 2018Trial
- Monoclonal antibody passive experimental autoimmune myasthenia gravis: current progress and future directions.Cell & bioscience · 2026Review
- Comprehensive review on myasthenia gravis: patho-physiology, diagnosis, management strategies.Wiener medizinische Wochenschrift (1946) · 2026Review
- Low Prevalence and Inconsistency of LRP4-IgG Detection in Suspected Myasthenia Gravis: A Multicenter CBA Comparison.Neurology(R) neuroimmunology & neuroinflammation · 2026Observational
- Complement deposition, IgG subtyping and endplate destruction in LRP4-ab-positive myasthenia gravis.Acta neuropathologica communications · 2026Observational
- Diagnostic Challenges of LRP4 Antibody Testing in Myasthenia Gravis: A Case Series of Four LRP4 Positive Cases With Uncertain Diagnostic Significance.Case reports in neurological medicine · 2026Article
- MuSK myasthenia gravis: from antigen-antibody to clinical translation.Frontiers in immunology · 2026Review
- Structural Proteins at Neuromuscular Junction Are Downgraded While NRG1 and Agrin Gene Expression Increases After Muscle Injury.Biomedicines · 2025Article
- Immunological Targets in Generalized Myasthenia Gravis Treatment: Where Are We Going Now?Brain sciences · 2025Review
- Post-Translational Modifications of Lipoproteins: Emerging Players Linking Inflammation and Cardiovascular Disease in Rheumatoid Arthritis-A Narrative Review.International journal of molecular sciences · 2025Review
- MuSK cysteine-rich domain antibodies are pathogenic in a mouse model of autoimmune myasthenia gravis.The Journal of clinical investigation · 2025Article
- Therapeutic strategies targeting complement in myasthenia gravis patients.Journal of neurology · 2025Review
- Optimization of Induction Protocols for Experimental Autoimmune Myasthenia Gravis.International journal of molecular sciences · 2025Article
- Targeting the Neonatal Fc Receptor in Autoimmune Diseases: Pipeline and Progress.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025Review
- Consensus guidelines on the diagnosis and management of myasthenia gravis by the Saudi Arabia Neuromuscular and Electrodiagnostic Medicine and neuromuscular specialists from the Gulf Cooperation Council region.Therapeutic advances in neurological disorders · 2025Review
- Heterogeneous Presentations and Serologies in Myasthenia Gravis Patients Presenting with Dysphagia.The Laryngoscope · 2024Article
- Sirt6 Mono-ADP-Ribosylates YY1 to Promote Dystrophin Expression for Neuromuscular Transmission.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- The MuSK agonist antibody protects the neuromuscular junction and extends the lifespan in C9orf72-ALS mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- FcRn Inhibitor Therapies in Neurologic Diseases.CNS drugs · 2024Review
- Building, Breaking, and Repairing Neuromuscular Synapses.Cold Spring Harbor perspectives in biology · 2024Review
39 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Myasthenia gravis (MG) is the most common disorder affecting the neuromuscular junction (NMJ). MG is frequently caused by autoantibodies against acetylcholine receptor (AChR) and a kinase critical for NMJ formation, MuSK; however, a proportion of MG patients are double-negative for anti-AChR and anti-MuSK antibodies. Recent studies in these subjects have identified autoantibodies against low-density lipoprotein receptor-related protein 4 (LRP4), an agrin receptor also critical for NMJ formation. LRP4 autoantibodies have not previously been implicated in MG pathogenesis. Here we demonstrate that mice immunized with the extracellular domain of LRP4 generated anti-LRP4 antibodies and exhibited MG-associated symptoms, including muscle weakness, reduced compound muscle action potentials (CMAPs), and compromised neuromuscular transmission. Additionally, fragmented and distorted NMJs were evident at both the light microscopic and electron microscopic levels. We found that anti-LRP4 sera decreased cell surface LRP4 levels, inhibited agrin-induced MuSK activation and AChR clustering, and activated complements, revealing potential pathophysiological mechanisms. To further confirm the pathogenicity of LRP4 antibodies, we transferred IgGs purified from LRP4-immunized rabbits into naive mice and found that they exhibited MG-like symptoms, including reduced CMAP and impaired neuromuscular transmission. Together, these data demonstrate that LRP4 autoantibodies induce MG and that LRP4 contributes to NMJ maintenance in adulthood.
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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.