Evidence map›Paper›PMID 34724042›Full record

ArticleInflammatory bowel diseases2022

Neutrophil Extracellular Trap Density Increases With Increasing Histopathological Severity of Crohn's Disease.

Angie L Schroder, Belal Chami, Yuyang Liu, Chloe M Doyle, Mary El Kazzi, Golo Ahlenstiel, Gulfam Ahmad, Nimalan Pathma-Nathan, Geoff Collins, James Toh and 4 more

Open access · hybridAbstract read
In one paragraph

Article in Inflammatory bowel diseases, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed, 1 pooled it
3.1field-weighted citation impact, top 7% 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

38 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.

  1. Pooled it
  2. Nutrients · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 4 institutions in 1 country.

Angie L SchroderThe University of Sydney, School of Medical Sciences, Faculty of Medicine and Health, NSW, Australia.
Belal ChamiThe University of Sydney, School of Medical Sciences, Faculty of Medicine and Health, NSW, Australia.
Yuyang LiuThe University of Sydney, School of Medical Sciences, Faculty of Medicine and Health, NSW, Australia.
Chloe M DoyleThe University of Sydney, School of Medical Sciences, Faculty of Medicine and Health, NSW, Australia.
Mary El KazziThe University of Sydney, School of Medical Sciences, Faculty of Medicine and Health, NSW, Australia.
Golo AhlenstielWestern Sydney University, Westmead Clinical School and The Westmead Institute for Medical Research, Blacktown Hospital, Blacktown, NSW, Australia.ORCID 0000-0003-0026-1457
Gulfam AhmadThe University of Sydney, School of Medical Sciences, Faculty of Medicine and Health, NSW, Australia.
Nimalan Pathma-NathanWestmead Institute for Medical Research, Centre for Immunology and Allergy Research, Westmead, NSW, Australia.
Geoff CollinsWestmead Institute for Medical Research, Centre for Immunology and Allergy Research, Westmead, NSW, Australia.
James TohWestmead Institute for Medical Research, Centre for Immunology and Allergy Research, Westmead, NSW, Australia.
Andrew HarmanThe University of Sydney, School of Medical Sciences, Faculty of Medicine and Health, NSW, Australia.
Scott ByrneThe University of Sydney, School of Medical Sciences, Faculty of Medicine and Health, NSW, Australia.
Grahame CterctekoWestmead Institute for Medical Research, Centre for Immunology and Allergy Research, Westmead, NSW, Australia.
Paul K WittingThe University of Sydney, School of Medical Sciences, Faculty of Medicine and Health, NSW, Australia.ORCID 0000-0003-2237-7004
The University of Sydney · AUWestmead Hospital · AUWestmead Institute for Medical Research · AUBlacktown & Mount Druitt Hospital · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundIntestinal neutrophil recruitment is a characteristic feature of the earliest stages of inflammatory bowel disease (IBD). Neutrophil elastase (NE) and myeloperoxidase (MPO) mediate the formation of neutrophil extracellular traps (NETs); NETs produce the bactericidal oxidant hypochlorous acid (HOCl), causing host tissue damage when unregulated. The project aim was to investigate the relationship between NET formation and clinical IBD in humans.

methodsHuman intestinal biopsies were collected from Crohn's disease (CD) patients, endoscopically categorized as unaffected, transitional, or diseased, and assigned a histopathological score.

resultsA significant linear correlation was identified between pathological score and cell viability (TUNEL+). Immunohistochemical analysis revealed the presence of NET markers NE, MPO, and citrullinated histone (CitH3) that increased significantly with increasing histopathological score. Diseased specimens showed greater MPO+-immunostaining than control (P < .0001) and unaffected CD (P < .0001), with transitional CD specimens also showing greater staining than controls (P < .05) and unaffected CD (P < .05). Similarly, NE+-immunostaining was elevated significantly in diseased CD than controls (P < .0001) and unaffected CD (P < .0001) and was significantly higher in transitional CD than in controls (P < .0001) and unaffected CD (P < .0001). The CitH3+-immunostaining of diseased CD was significantly higher than controls (P < .05), unaffected CD (P < .0001) and transitional CD (P < .05), with transitional CD specimens showing greater staining than unaffected CD (P < .01). Multiplex immunohistochemistry with z-stacking revealed colocalization of NE, MPO, CitH3, and DAPI (cell nuclei), confirming the NET assignment.

conclusionThese data indicate an association between increased NET formation and CD severity, potentially due to excessive MPO-mediated HOCl production in the extracellular domain, causing host tissue damage that exacerbates CD.

Indexed as

Crohn DiseaseExtracellular TrapsHistonesHumansNeutrophil InfiltrationNeutrophilsPeroxidaseHistonesPeroxidaseinflammatory bowel diseasemyeloperoxidaseneutrophil extracellular traps

Identifiers

PMID34724042
PMCPMC9036391
OpenAlexW3210441646

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.