Evidence map›Paper›PMID 23645838›Full record

ArticleBlood2013

Inhibition of HPA-1a alloantibody-mediated platelet destruction by a deglycosylated anti-HPA-1a monoclonal antibody in mice: toward targeted treatment of fetal-alloimmune thrombocytopenia.

Tamam Bakchoul, Andreas Greinacher, Ulrich J Sachs, Annika Krautwurst, Harald Renz, Habi Harb, Gregor Bein, Peter J Newman, Sentot Santoso

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
3.7field-weighted citation impact, top 6% 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

24 citing papers in PubMed, 51 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Frontiers in immunology · 2023
    Article
  6. Article
  7. Article
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  12. FcRn, but not FcγRs, drives maternal-fetal transplacental transport of human IgG antibodies.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  13. Review
  14. Article
  15. Article
  16. Article
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  18. Article
  19. Review
  20. Fetal/Neonatal Alloimmune Thrombocytopenia: Pathogenesis, Diagnostics and Prevention.Archivum immunologiae et therapiae experimentalis · 2016
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 2 countries.

Tamam BakchoulInstitute for Immunology and Transfusion Medicine, Ernst Moritz Arndt University, Greifswald, Germany.
Andreas Greinacher
Ulrich J Sachs
Annika Krautwurst
Harald Renz
Habi Harb
Gregor Bein
Peter J Newman
Sentot Santoso
University of Giessen · DEPhilipps University of Marburg · DEVersiti Blood Center of Wisconsin · US

Funding

Transgenic/Knockout CoreP01HL044612 · NHLBI · VERSITI WISCONSIN, INC. · PI NEWMAN, PETER J · 1990 to 2015
$33.4M
NHLBI NIH HHS HL44612NHLBI NIH HHS P01 HL044612
6 · The paper itself

Abstract

Fetal/neonatal alloimmune thrombocytopenia (FNAIT) is often caused by maternal alloantibodies against the human platelet antigen (HPA)-1a, which opsonizes fetal platelets (PLTs). Subsequent PLT destruction is mediated via the Fc part of the alloantibodies. The monoclonal antibody (mAb) SZ21 binds to the HPA-1a epitope and inhibits the binding of maternal alloantibodies. However, it also promotes complement activation and phagocytosis. Deglycosylation of antibodies abrogates the Fc-related effector functions. We modified the N-glycan of SZ21 by endoglycosidase F. The in vivo transplacental transport of N-glycan-modified (NGM)-SZ21 was not impaired. When injected into pregnant mice, both native-SZ21 and NGM-SZ21 were transported equally into fetal circulation (8.9% vs 8.7%, respectively, P = .58). Neither the binding properties of NGM-SZ21 to HPA-1a in surface plasmon resonance, nor the inhibition of anti-HPA-1a-induced PLT phagocytosis, were affected by N-glycan modification. NGM-SZ21 prevented PLT destruction induced by maternal anti-HPA-1a antibodies in vivo in a mouse model (PLT clearance after 5 hours; 18% vs 62%, in the presence or absence of NGM-SZ21, respectively, P = .013). Deglycosylation of SZ21 abrogates Fc-effector functions without interfering with placental transport or the ability to block anti-HPA-1a binding. Humanized, deglycosylated anti-HPA-1a mAbs may represent a novel treatment strategy to prevent anti-HPA-1a-mediated PLT destruction in FNAIT.

Indexed as

Molecular Targeted TherapyAnimalsAntibodies, MonoclonalAntigens, Human PlateletBiological TransportBlood PlateletsDisease Models, AnimalFemaleGlycosylationHumansIntegrin beta3IsoantibodiesMannosyl-Glycoprotein Endo-beta-N-AcetylglucosaminidaseMiceMice, Inbred BALB CMice, SCIDAntibodies, MonoclonalAntigens, Human PlateletIntegrin beta3IsoantibodiesITGB3 protein, humanMannosyl-Glycoprotein Endo-beta-N-AcetylglucosaminidasePolysaccharides

Identifiers

PMID23645838
PMCPMC3716199
OpenAlexW2052265126

What OpenQuestion holds

Textmetadata
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.