Evidence map›Paper›PMID 34233932›Full record

ArticleNeurology2021

Characterization of LRP4/Agrin Antibodies From a Patient With Myasthenia Gravis.

Zheng Yu, Meiying Zhang, Hongyang Jing, Peng Chen, Rangjuan Cao, Jinxiu Pan, Bin Luo, Yue Yu, Brandy M Quarles, Wencheng Xiong and 2 more

Open access · greenAbstract readComment
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 1 pooled it
2.7field-weighted citation impact, top 8% 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

16 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Observational
  4. Review
  5. Article
  6. Review
  7. Review
  8. Myasthenia gravis: the future is here.The Journal of clinical investigation · 2024
    Review
  9. Functional Signature of LRP4 Antibodies in Myasthenia Gravis.Neurology(R) neuroimmunology & neuroinflammation · 2024
    Article
  10. Article
  11. Pathophysiology of Childhood-Onset Myasthenia: Abnormalities of Neuromuscular Junction and Autoimmunity and Its Background.Pathophysiology : the official journal of the International Society for Pathophysiology · 2023
    Review
  12. Article
  13. Review
  14. Article
  15. Article
  16. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 1 institution in 1 country.

Zheng YuFrom the Department of Neurosciences (Z.Y., M.Z., H.J., P.C., R.C., J.P., B.L., W.X., L.M.), School of Medicine, Case Western Reserve University, Cleveland; Beachwood High School (Y.Y.), OH; Department of Neurology (B.M.Q., M.H.R.), Augusta University, GA; and Louis Stokes Cleveland Veterans Affairs Medical Center (W.X., L.M.), OH.
Meiying ZhangFrom the Department of Neurosciences (Z.Y., M.Z., H.J., P.C., R.C., J.P., B.L., W.X., L.M.), School of Medicine, Case Western Reserve University, Cleveland; Beachwood High School (Y.Y.), OH; Department of Neurology (B.M.Q., M.H.R.), Augusta University, GA; and Louis Stokes Cleveland Veterans Affairs Medical Center (W.X., L.M.), OH.
Hongyang JingFrom the Department of Neurosciences (Z.Y., M.Z., H.J., P.C., R.C., J.P., B.L., W.X., L.M.), School of Medicine, Case Western Reserve University, Cleveland; Beachwood High School (Y.Y.), OH; Department of Neurology (B.M.Q., M.H.R.), Augusta University, GA; and Louis Stokes Cleveland Veterans Affairs Medical Center (W.X., L.M.), OH.
Peng ChenFrom the Department of Neurosciences (Z.Y., M.Z., H.J., P.C., R.C., J.P., B.L., W.X., L.M.), School of Medicine, Case Western Reserve University, Cleveland; Beachwood High School (Y.Y.), OH; Department of Neurology (B.M.Q., M.H.R.), Augusta University, GA; and Louis Stokes Cleveland Veterans Affairs Medical Center (W.X., L.M.), OH.
Rangjuan CaoFrom the Department of Neurosciences (Z.Y., M.Z., H.J., P.C., R.C., J.P., B.L., W.X., L.M.), School of Medicine, Case Western Reserve University, Cleveland; Beachwood High School (Y.Y.), OH; Department of Neurology (B.M.Q., M.H.R.), Augusta University, GA; and Louis Stokes Cleveland Veterans Affairs Medical Center (W.X., L.M.), OH.
Jinxiu PanFrom the Department of Neurosciences (Z.Y., M.Z., H.J., P.C., R.C., J.P., B.L., W.X., L.M.), School of Medicine, Case Western Reserve University, Cleveland; Beachwood High School (Y.Y.), OH; Department of Neurology (B.M.Q., M.H.R.), Augusta University, GA; and Louis Stokes Cleveland Veterans Affairs Medical Center (W.X., L.M.), OH.
Bin LuoFrom the Department of Neurosciences (Z.Y., M.Z., H.J., P.C., R.C., J.P., B.L., W.X., L.M.), School of Medicine, Case Western Reserve University, Cleveland; Beachwood High School (Y.Y.), OH; Department of Neurology (B.M.Q., M.H.R.), Augusta University, GA; and Louis Stokes Cleveland Veterans Affairs Medical Center (W.X., L.M.), OH.
Yue YuFrom the Department of Neurosciences (Z.Y., M.Z., H.J., P.C., R.C., J.P., B.L., W.X., L.M.), School of Medicine, Case Western Reserve University, Cleveland; Beachwood High School (Y.Y.), OH; Department of Neurology (B.M.Q., M.H.R.), Augusta University, GA; and Louis Stokes Cleveland Veterans Affairs Medical Center (W.X., L.M.), OH.
Brandy M QuarlesFrom the Department of Neurosciences (Z.Y., M.Z., H.J., P.C., R.C., J.P., B.L., W.X., L.M.), School of Medicine, Case Western Reserve University, Cleveland; Beachwood High School (Y.Y.), OH; Department of Neurology (B.M.Q., M.H.R.), Augusta University, GA; and Louis Stokes Cleveland Veterans Affairs Medical Center (W.X., L.M.), OH.
Wencheng XiongFrom the Department of Neurosciences (Z.Y., M.Z., H.J., P.C., R.C., J.P., B.L., W.X., L.M.), School of Medicine, Case Western Reserve University, Cleveland; Beachwood High School (Y.Y.), OH; Department of Neurology (B.M.Q., M.H.R.), Augusta University, GA; and Louis Stokes Cleveland Veterans Affairs Medical Center (W.X., L.M.), OH.
Michael H RivnerFrom the Department of Neurosciences (Z.Y., M.Z., H.J., P.C., R.C., J.P., B.L., W.X., L.M.), School of Medicine, Case Western Reserve University, Cleveland; Beachwood High School (Y.Y.), OH; Department of Neurology (B.M.Q., M.H.R.), Augusta University, GA; and Louis Stokes Cleveland Veterans Affairs Medical Center (W.X., L.M.), OH. lin.mei@case.edu mrivner@augusta.edu.
Lin MeiFrom the Department of Neurosciences (Z.Y., M.Z., H.J., P.C., R.C., J.P., B.L., W.X., L.M.), School of Medicine, Case Western Reserve University, Cleveland; Beachwood High School (Y.Y.), OH; Department of Neurology (B.M.Q., M.H.R.), Augusta University, GA; and Louis Stokes Cleveland Veterans Affairs Medical Center (W.X., L.M.), OH. lin.mei@case.edu mrivner@augusta.edu.
Augusta University · US

Funding

Characterization of Agrin/LRP4 Antibody-Positive Myasthenia GravisR01NS090083 · NINDS · CASE WESTERN RESERVE UNIVERSITY · PI MEI, LIN · 2015 to 2019
$2.9M
NINDS NIH HHS R01 NS090083
6 · The paper itself

Abstract

BACKGROUND AND

objectiveTo determine whether human anti-LRP4/agrin antibodies are pathogenic in mice and to investigate underpinning pathogenic mechanisms.

methodsImmunoglobulin (Ig) was purified from a patient with myasthenia gravis (MG) with anti-LRP4/agrin antibodies and transferred to mice. Mice were characterized for body weight, muscle strength, twitch and tetanic force, neuromuscular junction (NMJ) functions including compound muscle action potential (CMAP) and endplate potentials, and NMJ structure. Effects of the antibodies on agrin-elicited muscle-specific tyrosine kinase (MuSK) activation and AChR clustering were studied and the epitopes of these antibodies were identified.

resultsPatient Ig-injected mice had MG symptoms, including weight loss and muscle weakness. Decreased CMAPs, reduced twitch and tetanus force, compromised neuromuscular transmission, and NMJ fragmentation and distortion were detected in patient Ig-injected mice. Patient Ig inhibited agrin-elicited MuSK activation and AChR clustering. The patient Ig recognized the β3 domain of LRP4 and the C-terminus of agrin and reduced agrin-enhanced LRP4-MuSK interaction. DISCUSSION: Anti-LRP4/agrin antibodies in the patient with MG is pathogenic. It impairs the NMJ by interrupting agrin-dependent LRP4-MuSK interaction.

Indexed as

AgrinMyasthenia GravisAnimalsAntibodiesHumansLDL-Receptor Related ProteinsMiceNeuromuscular JunctionAgrinAntibodiesLDL-Receptor Related ProteinsLRP4 protein, humanLrp4 protein, mouse

Identifiers

PMID34233932
PMCPMC8448554
OpenAlexW3182492511

What OpenQuestion holds

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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.