Evidence map›Paper›PMID 25130613›Full record

ArticleEuropean journal of immunology2014

Carbamylation of immunoglobulin abrogates activation of the classical complement pathway.

Catalin Koro, Ewa Bielecka, Anders Dahl-Knudsen, Jan J Enghild, Carsten Scavenius, Johan G Brun, Veronika Binder, Annelie Hellvard, Brith Bergum, Roland Jonsson and 3 more

Open access · hybridAbstract read
In one paragraph

Article in European journal of immunology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.9field-weighted citation impact, top 15% 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

15 citing papers in PubMed, 26 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Mechanisms and consequences of carbamoylation.Nature reviews. Nephrology · 2017
    Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Protein carbamylation is a hallmark of aging.Proceedings of the National Academy of Sciences of the United States of America · 2016
    Article
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

13 authors at 5 institutions in 5 countries.

Catalin KoroBroegelmann Research Laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway.
Ewa Bielecka
Anders Dahl-Knudsen
Jan J Enghild
Carsten Scavenius
Johan G Brun
Veronika Binder
Annelie Hellvard
Brith Bergum
Roland Jonsson
Jan Potempa
Anna M Blom
Piotr Mydel
University of Bergen · NOAarhus University · DKJagiellonian University · PLHaukeland University Hospital · NOLund University · SE

Funding

BACTERIAL PROTEINASES IN PERIODONTAL DISEASER01DE009761 · NIDCR · UNIVERSITY OF LOUISVILLE · PI POTEMPA, JAN S · 1991 to 2012
$3.8M
Bacterial peptidylarginine deiminase, a link between gums and joint diseaseR01DE022597 · NIDCR · UNIVERSITY OF LOUISVILLE · PI POTEMPA, JAN S · 2013 to 2023
$3.7M
NIDCR NIH HHS DE 022597NIDCR NIH HHS DE 09761NIDCR NIH HHS R01 DE009761NIDCR NIH HHS R01 DE022597
6 · The paper itself

Abstract

Post-translational modifications of proteins significantly affect their structure and function. The carbamylation of positively charged lysine residues to form neutral homoitrulline occurs primarily under inflammatory conditions through myeloperoxidase-dependent cyanate (CNO-) formation. We analyzed the pattern of human IgG1 carbamylation under inflammatory conditions and the effects that this modification has on the ability of antibodies to trigger complement activation via the classical pathway. We found that the lysine residues of IgG1 are rapidly modified after brief exposure to CNO- . Interestingly, modifications were not random, but instead limited to only few lysines within the hinge area and the N-terminal fragment of the CH2 domain. A complement activation assay combined with mass spectrometry analysis revealed a highly significant inverse correlation between carbamylation of several key lysine residues within the hinge region and N-terminus of the CH2 domain and the proper binding of C1q to human IgG1 followed by subsequent complement activation. This severely hindered complement-dependent cytotoxicity of therapeutic IgG1 . The reaction can apparently occur in vivo, as we found carbamylated antibodies in synovial fluid from rheumatoid arthritis patients. Taken together, our data suggest that carbamylation has a profound impact on the complement-activating ability of IgG1 and reveals a pivotal role for previously uncharacterized lysine residues in this process.

Indexed as

Adhesins, BacterialAntibodies, Monoclonal, Murine-DerivedAntibody-Dependent Cell CytotoxicityArthritis, RheumatoidCitrullineComplement ActivationComplement C1qComplement Pathway, ClassicalCyanatesCysteine EndopeptidasesGingipain Cysteine EndopeptidasesHumansImmunoglobulin GImmunologic FactorsInflammationLysineAdhesins, BacterialAntibodies, Monoclonal, Murine-DerivedCitrullineComplement C1qCyanatesCysteine EndopeptidasesGingipain Cysteine EndopeptidaseshomocitrullineImmunoglobulin GImmunologic FactorsLysineRituximabCarbamylationComplementIgG1InflammationRheumatoid arthritis

Identifiers

PMID25130613
PMCPMC4232992
OpenAlexW2036847148

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.