Evidence map›Paper›PMID 30882021›Full record

ArticleNeurology(R) neuroimmunology & neuroinflammation2019

MuSK myasthenia gravis monoclonal antibodies: Valency dictates pathogenicity.

Maartje G Huijbers, Dana L Vergoossen, Yvonne E Fillié-Grijpma, Inge E van Es, Marvyn T Koning, Linda M Slot, Hendrik Veelken, Jaap J Plomp, Silvère M van der Maarel, Jan J Verschuuren

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

Article in Neurology(R) neuroimmunology & neuroinflammation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed
8.8field-weighted citation impact, top 2% 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

61 citing papers in PubMed, 94 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. Review
  9. Review
  10. Review
  11. Autoimmune encephalitis.Nature reviews. Disease primers · 2025
    Review
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Review
  18. Agonist antibody to MuSK protects mice from MuSK myasthenia gravis.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  19. Review
  20. Review

1 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 1 institution in 1 country.

Maartje G HuijbersDepartment of Neurology (M.G.H., Y.E.F.-G., I.E.v.E., J.J.P., J.J.V.), Department of Human Genetics (M.G.H., D.L.V., Y.F.-G., I.E.v.E., S.M.v.d.M.), Department of Hematology (M.T.K., H.V.), and Department of Rheumatology (L.M.S.), Leiden University Medical Center, The Netherlands.
Dana L VergoossenDepartment of Neurology (M.G.H., Y.E.F.-G., I.E.v.E., J.J.P., J.J.V.), Department of Human Genetics (M.G.H., D.L.V., Y.F.-G., I.E.v.E., S.M.v.d.M.), Department of Hematology (M.T.K., H.V.), and Department of Rheumatology (L.M.S.), Leiden University Medical Center, The Netherlands.
Yvonne E Fillié-GrijpmaDepartment of Neurology (M.G.H., Y.E.F.-G., I.E.v.E., J.J.P., J.J.V.), Department of Human Genetics (M.G.H., D.L.V., Y.F.-G., I.E.v.E., S.M.v.d.M.), Department of Hematology (M.T.K., H.V.), and Department of Rheumatology (L.M.S.), Leiden University Medical Center, The Netherlands.
Inge E van EsDepartment of Neurology (M.G.H., Y.E.F.-G., I.E.v.E., J.J.P., J.J.V.), Department of Human Genetics (M.G.H., D.L.V., Y.F.-G., I.E.v.E., S.M.v.d.M.), Department of Hematology (M.T.K., H.V.), and Department of Rheumatology (L.M.S.), Leiden University Medical Center, The Netherlands.
Marvyn T KoningDepartment of Neurology (M.G.H., Y.E.F.-G., I.E.v.E., J.J.P., J.J.V.), Department of Human Genetics (M.G.H., D.L.V., Y.F.-G., I.E.v.E., S.M.v.d.M.), Department of Hematology (M.T.K., H.V.), and Department of Rheumatology (L.M.S.), Leiden University Medical Center, The Netherlands.
Linda M SlotDepartment of Neurology (M.G.H., Y.E.F.-G., I.E.v.E., J.J.P., J.J.V.), Department of Human Genetics (M.G.H., D.L.V., Y.F.-G., I.E.v.E., S.M.v.d.M.), Department of Hematology (M.T.K., H.V.), and Department of Rheumatology (L.M.S.), Leiden University Medical Center, The Netherlands.
Hendrik VeelkenDepartment of Neurology (M.G.H., Y.E.F.-G., I.E.v.E., J.J.P., J.J.V.), Department of Human Genetics (M.G.H., D.L.V., Y.F.-G., I.E.v.E., S.M.v.d.M.), Department of Hematology (M.T.K., H.V.), and Department of Rheumatology (L.M.S.), Leiden University Medical Center, The Netherlands.
Jaap J PlompDepartment of Neurology (M.G.H., Y.E.F.-G., I.E.v.E., J.J.P., J.J.V.), Department of Human Genetics (M.G.H., D.L.V., Y.F.-G., I.E.v.E., S.M.v.d.M.), Department of Hematology (M.T.K., H.V.), and Department of Rheumatology (L.M.S.), Leiden University Medical Center, The Netherlands.
Silvère M van der MaarelDepartment of Neurology (M.G.H., Y.E.F.-G., I.E.v.E., J.J.P., J.J.V.), Department of Human Genetics (M.G.H., D.L.V., Y.F.-G., I.E.v.E., S.M.v.d.M.), Department of Hematology (M.T.K., H.V.), and Department of Rheumatology (L.M.S.), Leiden University Medical Center, The Netherlands.
Jan J VerschuurenDepartment of Neurology (M.G.H., Y.E.F.-G., I.E.v.E., J.J.P., J.J.V.), Department of Human Genetics (M.G.H., D.L.V., Y.F.-G., I.E.v.E., S.M.v.d.M.), Department of Hematology (M.T.K., H.V.), and Department of Rheumatology (L.M.S.), Leiden University Medical Center, The Netherlands.
Amsterdam UMC Location Vrije Universiteit Amsterdam · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Objective: To isolate and characterize muscle-specific kinase (MuSK) monoclonal antibodies from patients with MuSK myasthenia gravis (MG) on a genetic and functional level. Methods: We generated recombinant MuSK antibodies from patient-derived clonal MuSK-specific B cells and produced monovalent Fab fragments from them. Both the antibodies and Fab fragments were tested for their effects on neural agrin-induced MuSK phosphorylation and acetylcholine receptor (AChR) clustering in myotube cultures. Results: The isolated MuSK monoclonal antibody sequences included IgG1, IgG3, and IgG4 that had undergone high levels of affinity maturation, consistent with antigenic selection. We confirmed their specificity for the MuSK Ig-like 1 domain and binding to neuromuscular junctions. Monovalent MuSK Fab, mimicking functionally monovalent MuSK MG patient Fab-arm exchanged serum IgG4, abolished agrin-induced MuSK phosphorylation and AChR clustering. Surprisingly, bivalent monospecific MuSK antibodies instead activated MuSK phosphorylation and partially induced AChR clustering, independent of agrin. Conclusions: Patient-derived MuSK antibodies can act either as MuSK agonist or MuSK antagonist, depending on the number of MuSK binding sites. Functional monovalency, induced by Fab-arm exchange in patient serum, makes MuSK IgG4 antibodies pathogenic.

Indexed as

AdultAntibodies, MonoclonalAutoantibodiesCells, CulturedHumansMuscle Fibers, SkeletalMyasthenia GravisReceptor Protein-Tyrosine KinasesReceptors, CholinergicRecombinant ProteinsAntibodies, MonoclonalAutoantibodiesMUSK protein, humanReceptor Protein-Tyrosine KinasesReceptors, CholinergicRecombinant Proteins

Identifiers

PMID30882021
PMCPMC6410930
OpenAlexW2917058438

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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 OpenQuestion graph.