Evidence map›Paper›PMID 41233527›Full record

ArticleCommunications biology2025

Pyroglutamation of cell surface proteins CD47 and TRP1 by glutaminyl cyclase modulates therapeutic antibody binding.

Anneloes van der Plas-van Duijn, Levi M T Winkelman, Claire Lensen, Maaike van Duivendijk, Ian Derksen, Jacqueline M F van Veenendaal, Gaby Schaap, Marjolein Sluijter, Tim J B van Groningen, Remco van Doorn and 6 more

Abstract read
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In one paragraph

Article in Communications biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Review
  2. Melanocyte loss dominates the vitiligo transcriptome: a rank-based meta-analysis.medRxiv : the preprint server for health sciences · 2026
    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

16 authors.

Anneloes van der Plas-van DuijnDepartment of Dermatology, Leiden University Medical Center, Leiden, the Netherlands.ORCID http://orcid.org/0000-0003-4708-0952
Levi M T WinkelmanDivision of Cell Systems and Drug Safety, Leiden Academic Centre for Drug Research, Leiden University, Leiden, the Netherlands.ORCID http://orcid.org/0009-0001-9105-7840
Claire LensenDepartment of Dermatology, Leiden University Medical Center, Leiden, the Netherlands.
Maaike van DuivendijkDepartment of Dermatology, Leiden University Medical Center, Leiden, the Netherlands.
Ian DerksenDepartment of Dermatology, Leiden University Medical Center, Leiden, the Netherlands.
Jacqueline M F van VeenendaalDepartment of Dermatology, Leiden University Medical Center, Leiden, the Netherlands.ORCID http://orcid.org/0009-0006-0519-9292
Gaby SchaapDepartment of Medical Oncology, Oncode institute, Leiden University Medical Center, Leiden, the Netherlands.
Marjolein SluijterDepartment of Medical Oncology, Oncode institute, Leiden University Medical Center, Leiden, the Netherlands.
Tim J B van GroningenDepartment of Dermatology, Leiden University Medical Center, Leiden, the Netherlands.ORCID http://orcid.org/0000-0002-5851-5192
Remco van DoornDepartment of Dermatology, Leiden University Medical Center, Leiden, the Netherlands.
Thorbald van HallDepartment of Medical Oncology, Oncode institute, Leiden University Medical Center, Leiden, the Netherlands.ORCID http://orcid.org/0000-0002-9115-558X
Roderick C SliekerDepartment of Dermatology, Leiden University Medical Center, Leiden, the Netherlands.ORCID http://orcid.org/0000-0003-0961-9152
Thomas H SharpSchool of Biochemistry, University of Bristol, Bristol, United Kingdom.ORCID http://orcid.org/0000-0002-1990-2333
Joost B BeltmanDivision of Cell Systems and Drug Safety, Leiden Academic Centre for Drug Research, Leiden University, Leiden, the Netherlands.ORCID http://orcid.org/0000-0001-9215-3087
Kaspar BresserT Cell Differentiation Lab, Department of Research, Sanquin Blood Supply Foundation, Amsterdam, the Netherlands.
Ferenc A ScheerenDepartment of Dermatology, Leiden University Medical Center, Leiden, the Netherlands. f.a.scheeren@lumc.nl.ORCID http://orcid.org/0000-0002-8304-9023

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Monoclonal antibodies are important modalities in the treatment of cancer. Post-translational modifications of proteins, such as glycosylation, can affect the binding affinity of therapeutic antibodies. Whether other PTMs modulate therapeutic antibody binding to different surface proteins is currently underexplored. Pyroglutamation is the post-translational cyclization of an N-terminal glutamine or glutamic acid residue into a pyroglutamate by glutaminyl cyclase. In this study, we investigated the impact of pyroglutamation on the binding affinity of three therapeutic antibodies targeting CD47 and TRP1. Here, we show that pyroglutamation on CD47 and TRP1 modulates the binding of anti(α)-CD47 magrolimab and αTRP1 TA99 and flanvotumab. Furthermore, the N-terminal glutamine on CD47 is crucial for effective antibody recognition, while pyroglutamation of TRP1 is involved in trafficking to the cell surface. These findings highlight that the pyroglutamation by glutaminyl cyclase can modulate the binding affinity of antibodies with therapeutic potential.

Indexed as

AminoacyltransferasesAntibodies, MonoclonalCD47 AntigenPyrrolidonecarboxylic AcidAnimalsAntibodies, Monoclonal, HumanizedHumansProtein BindingProtein Processing, Post-TranslationalAminoacyltransferasesAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedCD47 AntigenCD47 protein, humanglutaminyl-peptide cyclotransferasePyrrolidonecarboxylic Acid

Identifiers

PMID41233527
PMCPMC12615796

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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.