Evidence map›Paper›PMID 21814823›Full record

ArticleJournal of neurology2012

Anti-LRP4 autoantibodies in AChR- and MuSK-antibody-negative myasthenia gravis.

Alexandra Pevzner, Benedikt Schoser, Katja Peters, Nicoleta-Carmen Cosma, Andromachi Karakatsani, Berthold Schalke, Arthur Melms, Stephan Kröger

Abstract read
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In one paragraph

Article in Journal of neurology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
124citing papers in PubMed, 6 pooled it
16.7field-weighted citation impact, top 1% 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

124 citing papers in PubMed, 6 syntheses or guidelines pooled it, 334 citations in OpenAlex.

  1. Pooled it
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  6. Thymectomy for non-thymomatous myasthenia gravis.The Cochrane database of systematic reviews · 2013
    Pooled it
  7. Trial
  8. 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 · 2013
    Trial
  9. Review
  10. Review
  11. Observational
  12. Observational
  13. Article
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  15. Article
  16. Open-label study of efgartigimod in seronegative myasthenia gravis.Therapeutic advances in neurological disorders · 2025
    Article
  17. Article
  18. Article
  19. Review
  20. Article

64 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

8 authors at 3 institutions in 1 country.

Alexandra PevznerDepartment of Physiological Genomics, Institute for Physiology, Ludwig-Maximilians University, Pettenkoferstrasse 12, 80336, Munich, Germany.
Benedikt Schoser
Katja Peters
Nicoleta-Carmen Cosma
Andromachi Karakatsani
Berthold Schalke
Arthur Melms
Stephan Kröger
Ludwig-Maximilians-Universität München · DEUniversity of Regensburg · DEUniversity of Tübingen · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Myasthenia gravis (MG) is an autoimmune disorder characterized by a defect in synaptic transmission at the neuromuscular junction causing fluctuating muscle weakness with a decremental response to repetitive nerve stimulation or altered jitter in single-fiber electromyography (EMG). Approximately 80% of all myasthenia gravis patients have autoantibodies against the nicotinic acetylcholine receptor in their serum. Autoantibodies against the tyrosine kinase muscle-specific kinase (MuSK) are responsible for 5-10% of all myasthenia gravis cases. The autoimmune target in the remaining cases is unknown. Recently, low-density lipoprotein receptor-related protein (LRP4) has been identified as the agrin receptor. LRP4 interacts with agrin, and the binding of agrin activates MuSK, which leads to the formation of most if not all postsynaptic specializations, including aggregates containing acetylcholine receptors (AChRs) in the junctional plasma membrane. In the present study we tested if autoantibodies against LRP4 are detectable in patients with myasthenia gravis. To this end we analyzed 13 sera from patients with generalized myasthenia gravis but without antibodies against AChR or MuSK. The results showed that 12 out of 13 antisera from double-seronegative MG patients bound to proteins concentrated at the neuromuscular junction of adult mouse skeletal muscle and that approximately 50% of the tested sera specifically bound to HEK293 cells transfected with human LRP4. Moreover, 4 out of these 13 sera inhibited agrin-induced aggregation of AChRs in cultured myotubes by more than 50%, suggesting a pathogenic role regarding the dysfunction of the neuromuscular endplate. These results indicate that LRP4 is a novel target for autoantibodies and is a diagnostic marker in seronegative MG patients.

Indexed as

AdolescentAdultAgedAgrinAnimalsAutoantibodiesBungarotoxinsCells, CulturedFemaleGreen Fluorescent ProteinsHumansLDL-Receptor Related ProteinsMaleMiceMiddle AgedMuscle Fibers, SkeletalAgrinAutoantibodiesBungarotoxinsenhanced green fluorescent proteinGreen Fluorescent ProteinsLDL-Receptor Related ProteinsLRP4 protein, humanReceptor Protein-Tyrosine KinasesReceptors, Nicotinic

Identifiers

PMID21814823
OpenAlexW1963748908

What OpenQuestion holds

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Read underepoch 390

Registered trials

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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.