Evidence map›Paper›PMID 34022940›Full record

ArticleArthritis research & therapy2021

Circulating mature granzyme B+ T cells distinguish Crohn's disease-associated axial spondyloarthritis from axial spondyloarthritis and Crohn's disease.

Adam R Lefferts, Emilie H Regner, Andrew Stahly, Becky O'Rourke, Mark E Gerich, Blair P Fennimore, Frank I Scott, Alison E Freeman, Ken Jones, Kristine A Kuhn

Abstract read
In one paragraph

Article in Arthritis research & therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing 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

9 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. DBI Mediates the Progression of Ankylosing Spondylitis by Regulating CD56Analytical cellular pathology (Amsterdam) · 2025
    Article
  5. Review
  6. Big Data in Gastroenterology Research.International journal of molecular sciences · 2023
    Review
  7. Article
  8. Review
  9. Review
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

10 authors.

Adam R Lefferts *Division of Rheumatology, Department of Medicine, Anschutz Medical Campus, Aurora, CO, USA.
Emilie H Regner *Division of Gastroenterology and Hepatology, Department of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.
Andrew StahlyDivision of Rheumatology, Department of Medicine, Anschutz Medical Campus, Aurora, CO, USA.
Becky O'RourkeSection of Pediatric Hematology/Oncology/Bone Marrow Transplant, Department of Pediatrics, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.
Mark E GerichDivision of Gastroenterology and Hepatology, Department of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.
Blair P FennimoreDivision of Gastroenterology and Hepatology, Department of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.
Frank I ScottDivision of Gastroenterology and Hepatology, Department of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.
Alison E FreemanDivision of Gastroenterology and Hepatology, Department of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.
Ken JonesSection of Pediatric Hematology/Oncology/Bone Marrow Transplant, Department of Pediatrics, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.
Kristine A KuhnDivision of Rheumatology, Department of Medicine, Anschutz Medical Campus, Aurora, CO, USA. kristine.kuhn@cuanschutz.edu.ORCID 0000-0002-6900-4195

Funding

Defining the role of altered cytokine signaling pathways on autoimmunityU01AI101990 · NIAID · BENAROYA RESEARCH INST AT VIRGINIA MASON · PI BUCKNER, JANE HOYT · 2012 to 2016
$12.1M
Prevention Center U01: Early Targets for Antigen-Specific Tolerance Induction in Preclinical Rheumatoid ArthritisU01AI101981 · NIAID · UNIVERSITY OF COLORADO DENVER · PI HOLERS, VERNON MICHAEL · 2012 to 2021
$6.2M
Research Training in Rheumatology INCLUDE Down Syndrome SupplementT32AR007534 · NIAMS · UNIVERSITY OF COLORADO DENVER · PI Kristine A. Kuhn · 1986 to 2026
$6.1M
Development of colonic intraepithelial lymphocytes and their role in epithelial and immune functionK08DK107905 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI KUHN, KRISTINE A. · 2016 to 2020
$716k
NIAID NIH HHS U01 AI101981NIAID NIH HHS U01 AI101990NIAMS NIH HHS T32 AR007534NIDDK NIH HHS K08 DK107905
6 · The paper itself

Abstract

backgroundAxial spondyloarthritis (axSpA) has strong connections with intestinal inflammation as occurs in Crohn's disease (CD). However, the immunologic mechanisms that distinguish axSpA, CD, and those with features of both diseases (CD-axSpA) are unknown. This study aimed to address this question by initial unbiased single cell RNA-sequencing (scRNAseq) on a pilot cohort followed by validating findings using flow cytometry and ELISA in a larger cohort.

methodsTwo individuals each with CD, axSpA, CD-axSpA, and healthy controls (HC) were recruited for a pilot discovery scRNAseq cohort, and the validation cohort consisted of 18 axSpA, 24 CD, 13 CD-axSpA, and 17 HC that was evaluated by flow cytometry on PBMCs and ELISAs for plasma cytokines.

resultsUniquely, PBMCs from subjects with CD-axSpA demonstrated a significant increase in granzyme B+ T cells of both CD4+ and CD8+ lineages by both scRNAseq and flow cytometry. T cell maturation was also greater in those with CD-axSpA, particularly the CD4+ granzyme B+ population. Pathway analysis suggested increased interferon response genes in all immune cell populations within CD-axSpA. Although IFN-γ was elevated in the plasma of a subset of subjects with CD-axSpA, IL-6 was also significantly elevated.

conclusionsOur findings support the presence of a chronic interferonopathy in subjects with CD-axSpA characterized by interferon signaling by pathway analysis and an expansion of mature, cytotoxic T cells. These data indicate fundamental immunological differences between CD-axSpA and both of the putative "parent" conditions, suggesting that it is a distinct disease with unique natural history and treatment needs.

Indexed as

Crohn DiseaseSpondylarthritisSpondylitis, AnkylosingGranzymesHumansT-LymphocytesGranzymesAnkylosing spondylitisAxial spondyloarthritisCrohn’s diseaseCytotoxic T cellsInflammatory bowel diseaseInterferonopathy

Identifiers

PMID34022940
PMCPMC8140495

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Registered trials

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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.