Evidence map›Paper›PMID 37582613›Full record

ArticleNeurology(R) neuroimmunology & neuroinflammation2023

IgG1-3 MuSK Antibodies Inhibit AChR Cluster Formation, Restored by SHP2 Inhibitor, Despite Normal MuSK, DOK7, or AChR Subunit Phosphorylation.

Michelangelo Cao, Wei-Wei Liu, Susan Maxwell, Saif Huda, Richard Webster, Amelia Evoli, David Beeson, Judith A Cossins, Angela Vincent

Erratum issuedOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurology(R) neuroimmunology & neuroinflammation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
2.5field-weighted citation impact, top 10% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 12 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Missing Full Disclosures.Neurology(R) neuroimmunology & neuroinflammation · 2025
    Article
  6. Review
  7. Review
  8. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 2 countries.

Michelangelo CaoFrom the Nuffield Department of Clinical Neurosciences (M.C., W.W.L., S.M., R.W., D.B., J.A.C., A.V.), University of Oxford; Norfolk and Norwich University Hospital (M.C.); The Walton Centre NHS Foundation Trust (S.H.), Liverpool, United Kingdom; and Department of Neuroscience (A.E.), Catholic University, Rome, Italy.ORCID 0000-0001-6249-2870
Wei-Wei LiuFrom the Nuffield Department of Clinical Neurosciences (M.C., W.W.L., S.M., R.W., D.B., J.A.C., A.V.), University of Oxford; Norfolk and Norwich University Hospital (M.C.); The Walton Centre NHS Foundation Trust (S.H.), Liverpool, United Kingdom; and Department of Neuroscience (A.E.), Catholic University, Rome, Italy.ORCID 0009-0003-2424-4990
Susan MaxwellFrom the Nuffield Department of Clinical Neurosciences (M.C., W.W.L., S.M., R.W., D.B., J.A.C., A.V.), University of Oxford; Norfolk and Norwich University Hospital (M.C.); The Walton Centre NHS Foundation Trust (S.H.), Liverpool, United Kingdom; and Department of Neuroscience (A.E.), Catholic University, Rome, Italy.ORCID 0009-0009-6514-149X
Saif HudaFrom the Nuffield Department of Clinical Neurosciences (M.C., W.W.L., S.M., R.W., D.B., J.A.C., A.V.), University of Oxford; Norfolk and Norwich University Hospital (M.C.); The Walton Centre NHS Foundation Trust (S.H.), Liverpool, United Kingdom; and Department of Neuroscience (A.E.), Catholic University, Rome, Italy.ORCID 0000-0003-0980-3750
Richard WebsterFrom the Nuffield Department of Clinical Neurosciences (M.C., W.W.L., S.M., R.W., D.B., J.A.C., A.V.), University of Oxford; Norfolk and Norwich University Hospital (M.C.); The Walton Centre NHS Foundation Trust (S.H.), Liverpool, United Kingdom; and Department of Neuroscience (A.E.), Catholic University, Rome, Italy.ORCID 0000-0001-7893-1348
Amelia EvoliFrom the Nuffield Department of Clinical Neurosciences (M.C., W.W.L., S.M., R.W., D.B., J.A.C., A.V.), University of Oxford; Norfolk and Norwich University Hospital (M.C.); The Walton Centre NHS Foundation Trust (S.H.), Liverpool, United Kingdom; and Department of Neuroscience (A.E.), Catholic University, Rome, Italy.
David BeesonFrom the Nuffield Department of Clinical Neurosciences (M.C., W.W.L., S.M., R.W., D.B., J.A.C., A.V.), University of Oxford; Norfolk and Norwich University Hospital (M.C.); The Walton Centre NHS Foundation Trust (S.H.), Liverpool, United Kingdom; and Department of Neuroscience (A.E.), Catholic University, Rome, Italy.ORCID 0000-0001-9395-7132
Judith A CossinsFrom the Nuffield Department of Clinical Neurosciences (M.C., W.W.L., S.M., R.W., D.B., J.A.C., A.V.), University of Oxford; Norfolk and Norwich University Hospital (M.C.); The Walton Centre NHS Foundation Trust (S.H.), Liverpool, United Kingdom; and Department of Neuroscience (A.E.), Catholic University, Rome, Italy.ORCID 0000-0003-2323-622X
Angela VincentFrom the Nuffield Department of Clinical Neurosciences (M.C., W.W.L., S.M., R.W., D.B., J.A.C., A.V.), University of Oxford; Norfolk and Norwich University Hospital (M.C.); The Walton Centre NHS Foundation Trust (S.H.), Liverpool, United Kingdom; and Department of Neuroscience (A.E.), Catholic University, Rome, Italy. angela.vincent@ndcn.ox.ac.uk.
University of Liverpool · GBNorfolk and Norwich University Hospitals NHS Foundation Trust · GB

Funding

Medical Research Council MR/M006824/1
6 · The paper itself

Abstract

BACKGROUND AND

objectivesUp to 50% of patients with myasthenia gravis (MG) without acetylcholine receptor antibodies (AChR-Abs) have antibodies to muscle-specific kinase (MuSK). Most MuSK antibodies (MuSK-Abs) are IgG4 and inhibit agrin-induced MuSK phosphorylation, leading to impaired clustering of AChRs at the developing or mature neuromuscular junction. However, IgG1-3 MuSK-Abs also exist in MuSK-MG patients, and their potential mechanisms have not been explored fully.

methodsC2C12 myotubes were exposed to MuSK-MG plasma IgG1-3 or IgG4, with or without purified agrin. MuSK, Downstream of Kinase 7 (DOK7), and βAChR were immunoprecipitated and their phosphorylation levels identified by immunoblotting. Agrin and agrin-independent AChR clusters were measured by immunofluorescence and AChR numbers by binding of

resultsIgG1-3 MuSK-Abs impaired AChR clustering without inhibiting agrin-induced MuSK phosphorylation. Moreover, the well-established pathway initiated by MuSK through DOK7, resulting in βAChR phosphorylation, was not impaired by MuSK-IgG1-3 and was agrin-independent. Nevertheless, the AChR clusters did not form, and both the number of AChR microclusters that precede full cluster formation and the myotube surface AChRs were reduced. Transcriptomic analysis did not throw light on the pathways involved. However, the SHP2 inhibitor, NSC-87877, increased the number of microclusters and led to fully formed AChR clusters. DISCUSSION: MuSK-IgG1-3 is pathogenic but seems to act through a noncanonical pathway. Further studies should throw light on the mechanisms involved at the neuromuscular junction.

Indexed as

Myasthenia GravisReceptor Protein-Tyrosine KinasesAgrinHumansImmunoglobulin GMuscle ProteinsPhosphorylationReceptors, CholinergicAgrinDOK7 protein, humanImmunoglobulin GMuscle ProteinsReceptor Protein-Tyrosine KinasesReceptors, Cholinergic

Identifiers

PMID37582613
PMCPMC10427144
OpenAlexW4385830178

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.