Evidence map›Paper›PMID 34862250›Full record

ArticleGut2022

Neutrophils prevent rectal bleeding in ulcerative colitis by peptidyl-arginine deiminase-4-dependent immunothrombosis.

Moritz Leppkes, Aylin Lindemann, Stefanie Gößwein, Susanne Paulus, Dominik Roth, Anne Hartung, Eva Liebing, Sebastian Zundler, Miguel Gonzalez-Acera, Jay V Patankar and 15 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Gut, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
3.8field-weighted citation impact, top 5% 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

47 citing papers in PubMed, 74 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Review
  5. Gut · 2026
    Article
  6. Review
  7. Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Review
  14. Beyond Killing: The Overlooked Contribution of Neutrophils to Tissue Repair.International journal of molecular sciences · 2025
    Review
  15. Review
  16. Article
  17. Article
  18. Article
  19. Neutrophils: emerging perspectives on the pathogenesis of oral mucosal diseases.Frontiers in cellular and infection microbiology · 2025
    Review
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

25 authors at 5 institutions in 1 country.

Moritz LeppkesMedical Clinic 1, University Clinic, Friedrich Alexander University, Erlangen, Germany moritz.leppkes@uk-erlangen.de.ORCID 0000-0003-2311-090X
Aylin LindemannMedical Clinic 1, University Clinic, Friedrich Alexander University, Erlangen, Germany.
Stefanie GößweinMedical Clinic 1, University Clinic, Friedrich Alexander University, Erlangen, Germany.
Susanne PaulusMedical Clinic 1, University Clinic, Friedrich Alexander University, Erlangen, Germany.
Dominik RothMedical Clinic 1, University Clinic, Friedrich Alexander University, Erlangen, Germany.
Anne HartungMedical Clinic 1, University Clinic, Friedrich Alexander University, Erlangen, Germany.
Eva LiebingMedical Clinic 1, University Clinic, Friedrich Alexander University, Erlangen, Germany.
Sebastian ZundlerMedical Clinic 1, University Clinic, Friedrich Alexander University, Erlangen, Germany.ORCID 0000-0003-0888-2784
Miguel Gonzalez-AceraMedical Clinic 1, University Clinic, Friedrich Alexander University, Erlangen, Germany.
Jay V PatankarMedical Clinic 1, University Clinic, Friedrich Alexander University, Erlangen, Germany.
Fabrizio MasciaMedical Clinic 1, University Clinic, Friedrich Alexander University, Erlangen, Germany.
Kristina ScheibeMedical Clinic 1, University Clinic, Friedrich Alexander University, Erlangen, Germany.
Markus HoffmannMedical Clinic 3, University Clinic, Friedrich Alexander University, Erlangen, Germany.
Stefan UderhardtDeutsches Zentrum Immuntherapie, Erlangen, Germany.
Christine SchauerMedical Clinic 3, University Clinic, Friedrich Alexander University, Erlangen, Germany.
Sebastian FoerschInstitute of Pathology, University Medical Center, Mainz, Germany.
Clemens NeufertMedical Clinic 1, University Clinic, Friedrich Alexander University, Erlangen, Germany.ORCID 0000-0003-1418-7921
Michael ViethFriedrich Alexander University, Institute of Pathology, Klinikum Bayreuth, Erlangen, Germany.
Georg SchettDeutsches Zentrum Immuntherapie, Erlangen, Germany.
Raja AtreyaMedical Clinic 1, University Clinic, Friedrich Alexander University, Erlangen, Germany.
Anja A KühlCharité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Andre BleichInstitute for Laboratory Animal Science, Hannover Medical School, Hannover, Germany.
Christoph BeckerMedical Clinic 1, University Clinic, Friedrich Alexander University, Erlangen, Germany.ORCID 0000-0002-1388-1041
Martin HerrmannMedical Clinic 3, University Clinic, Friedrich Alexander University, Erlangen, Germany.
Markus F NeurathMedical Clinic 1, University Clinic, Friedrich Alexander University, Erlangen, Germany.ORCID 0000-0003-4344-1474
Friedrich-Alexander-Universität Erlangen-Nürnberg · DEBayreuth Medical Center · DEHumboldt-Universität zu Berlin · DEJohannes Gutenberg University Mainz · DEMedizinische Hochschule Hannover · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveBleeding ulcers and erosions are hallmarks of active ulcerative colitis (UC). However, the mechanisms controlling bleeding and mucosal haemostasis remain elusive.

designWe used high-resolution endoscopy and colon tissue samples of active UC (n = 36) as well as experimental models of physical and chemical mucosal damage in mice deficient for peptidyl-arginine deiminase-4 (PAD4), gnotobiotic mice and controls. We employed endoscopy, histochemistry, live-cell microscopy and flow cytometry to study eroded mucosal surfaces during mucosal haemostasis.

resultsErosions and ulcerations in UC were covered by fresh blood, haematin or fibrin visible by endoscopy. Fibrin layers rather than fresh blood or haematin on erosions were inversely correlated with rectal bleeding in UC. Fibrin layers contained ample amounts of neutrophils coaggregated with neutrophil extracellular traps (NETs) with detectable activity of PAD. Transcriptome analyses showed significantly elevated

conclusionOur findings uncover that neutrophils induce secondary immunothrombosis by PAD4-dependent mechanisms. Insufficient immunothrombosis may favour rectal bleeding in UC.

Indexed as

Colitis, UlcerativeNeutrophilsAnimalsFibrinHydrolasesMiceProtein-Arginine Deiminase Type 4Thromboinflammationarginine deiminaseFibrinHydrolasesProtein-Arginine Deiminase Type 4bleedingIBDleukocytesmucosal injuryulcerative colitis

Identifiers

PMID34862250
PMCPMC9667856
OpenAlexW3216258971

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.