Evidence map›Paper›PMID 38776553›Full record

ArticleInflammatory bowel diseases2024

Activated HLA-DR+CD38+ Effector Th1/17 Cells Distinguish Crohn's Disease-associated Perianal Fistulas from Cryptoglandular Fistulas.

Laura F Ouboter, Ciska Lindelauf, Qinyue Jiang, Mette Schreurs, Tamim R Abdelaal, Sietse J Luk, Marieke C Barnhoorn, Willem E Hueting, Ingrid J Han-Geurts, Koen C M J Peeters and 4 more

Abstract read
In one paragraph

Article in Inflammatory bowel diseases, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed, 1 pooled it
–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 synthesis or guideline pooled it.

  1. Pooled it
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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

14 authors.

Laura F OuboterDepartment of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands.ORCID 0000-0002-7584-5644
Ciska LindelaufDepartment of Immunology, Leiden University Medical Center, Leiden, the Netherlands.
Qinyue JiangDepartment of Immunology, Leiden University Medical Center, Leiden, the Netherlands.
Mette SchreursDepartment of Immunology, Leiden University Medical Center, Leiden, the Netherlands.
Tamim R AbdelaalDepartment of Radiology, Leiden University Medical Center, Leiden, the Netherlands.
Sietse J LukDepartment of Hematology, Leiden University Medical Center, Leiden, the Netherlands.
Marieke C BarnhoornDepartment of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands.
Willem E HuetingDepartment of Surgery, Alrijne hospital, Leiderdorp, the Netherlands.
Ingrid J Han-GeurtsDepartment of Surgery, Proctos Clinic, Bilthoven, the Netherlands.
Koen C M J PeetersDepartment of Surgery, Leiden University Medical Center, Leiden, the Netherlands.
Fabian A HolmanDepartment of Surgery, Leiden University Medical Center, Leiden, the Netherlands.
Frits KoningDepartment of Immunology, Leiden University Medical Center, Leiden, the Netherlands.
Andrea E van der Meulen-de JongDepartment of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands.
Maria Fernanda PascuttiDepartment of Immunology, Leiden University Medical Center, Leiden, the Netherlands.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPerianal fistulas are a debilitating complication of Crohn's disease (CD). Due to unknown reasons, CD-associated fistulas are in general more difficult to treat than cryptoglandular fistulas (non-CD-associated). Understanding the immune cell landscape is a first step towards the development of more effective therapies for CD-associated fistulas. In this work, we characterized the composition and spatial localization of disease-associated immune cells in both types of perianal fistulas by high-dimensional analyses.

methodsWe applied single-cell mass cytometry (scMC), spectral flow cytometry (SFC), and imaging mass cytometry (IMC) to profile the immune compartment in CD-associated perianal fistulas and cryptoglandular fistulas. An exploratory cohort (CD fistula, n = 10; non-CD fistula, n = 5) was analyzed by scMC to unravel disease-associated immune cell types. SFC was performed on a second fistula cohort (CD, n = 10; non-CD, n = 11) to comprehensively phenotype disease-associated T helper (Th) cells. IMC was used on a third cohort (CD, n = 5) to investigate the spatial distribution/interaction of relevant immune cell subsets.

resultsOur analyses revealed that activated HLA-DR+CD38+ effector CD4+ T cells with a Th1/17 phenotype were significantly enriched in CD-associated compared with cryptoglandular fistulas. These cells, displaying features of proliferation, regulation, and differentiation, were also present in blood, and colocalized with other CD4+ T cells, CCR6+ B cells, and macrophages in the fistula tracts.

conclusionsOverall, proliferating activated HLA-DR+CD38+ effector Th1/17 cells distinguish CD-associated from cryptoglandular perianal fistulas and are a promising biomarker in blood to discriminate between these 2 fistula types. Targeting HLA-DR and CD38-expressing CD4+ T cells may offer a potential new therapeutic strategy for CD-related fistulas.

Indexed as

Crohn DiseaseHLA-DR AntigensRectal FistulaTh17 CellsTh1 CellsADP-ribosyl Cyclase 1AdultFemaleFlow CytometryHumansMaleMiddle AgedADP-ribosyl Cyclase 1HLA-DR AntigensCrohn’s diseasehigh-dimensional analysesperianal fistulas

Identifiers

PMID38776553
PMCPMC11812577

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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.