Evidence map›Paper›PMID 26841353›Full record

ArticleArthritis & rheumatology (Hoboken, N.J.)2016

Activation-Induced Killer Cell Immunoglobulin-like Receptor 3DL2 Binding to HLA-B27 Licenses Pathogenic T Cell Differentiation in Spondyloarthritis.

Anna Ridley, Hiroko Hatano, Isabel Wong-Baeza, Jacqueline Shaw, Katherine K Matthews, Hussein Al-Mossawi, Kristin Ladell, David A Price, Paul Bowness, Simon Kollnberger

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

Article in Arthritis & rheumatology (Hoboken, N.J.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
5.1field-weighted citation impact, top 4% 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

33 citing papers in PubMed, 52 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. Review
  10. Review
  11. Article
  12. Review
  13. Review
  14. Review
  15. Article
  16. Review
  17. Article
  18. Review
  19. Review
  20. 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 at 5 institutions in 4 countries.

Anna RidleyBotnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Oxford University, Oxford, UK.
Hiroko HatanoBotnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Oxford University, Oxford, UK.
Isabel Wong-BaezaIsabel Wong-Baeza, PhD: Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Oxford University, Oxford, UK, and National School of Biological Sciences, National Polytechnic Institute, Mexico City, Mexico.
Jacqueline ShawBotnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Oxford University, Oxford, UK.
Katherine K MatthewsQIMR, Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Hussein Al-MossawiBotnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Oxford University, Oxford, UK.
Kristin LadellCardiff University School of Medicine, Cardiff, UK.
David A PriceCardiff University School of Medicine, Cardiff, UK, and National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland.
Paul BownessBotnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Oxford University, Oxford, UK.
Simon KollnbergerBotnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, Oxford University, Oxford, UK, and Cardiff University School of Medicine, Cardiff, UK.
University of Oxford · GBCardiff University · GBNuffield Orthopaedic Centre · GBInstituto Politécnico Nacional · MXQIMR Berghofer Medical Research Institute · AU

Funding

Arthritis Research UKWellcome Trust
6 · The paper itself

Abstract

objectiveIn the spondyloarthritides (SpA), increased numbers of CD4+ T cells express killer cell immunoglobulin-like receptor 3DL2 (KIR-3DL2). The aim of this study was to determine the factors that induce KIR-3DL2 expression, and to characterize the relationship between HLA-B27 and the phenotype and function of KIR-3DL2-expressing CD4+ T cells in SpA.

methodsIn total, 34 B27+ patients with SpA, 28 age- and sex-matched healthy controls (20 B27- and 8 B27+), and 9 patients with rheumatoid arthritis were studied. KIR-3DL2 expression and other phenotypic characteristics of peripheral blood and synovial fluid CD4+ T cells were studied by flow cytometry, quantitative polymerase chain reaction, and Western blotting. T cell receptor clonality was determined by template-switch anchored reverse transcription-polymerase chain reaction and sequencing analysis. Cytokines were measured by enzyme-linked immunosorbent assay.

resultsCellular activation induced KIR-3DL2 expression on both naive and effector CD4+ T cells. KIR-3DL2 binding to B27+ cells promoted expression of KIR-3DL2, the Th17-specific transcription factor retinoic acid receptor-related orphan nuclear receptor γt, and the antiapoptotic factor B cell lymphoma 2. KIR-3DL2+CD4+ T cells in patients with ankylosing spondylitis were oligoclonal and enriched for markers of T cell activation and for the gut homing receptor CCR9. In the presence of B27+ antigen-presenting cells, KIR-3DL2+CD4+ T cells produced less interleukin-2 (IL-2) but more IL-17. This effect was blocked by HC10, an antibody that inhibits the binding of KIR-3DL2 to B27 heavy chains.

conclusionKIR-3DL2 binding to HLA-B27 licenses Th17 cell differentiation in SpA. These findings raise the therapeutic potential of targeting HLA-B27-KIR-3DL2 interactions for the treatment of B27+ patients with SpA.

Indexed as

AdultAgedArthritis, PsoriaticArthritis, ReactiveArthritis, RheumatoidBlotting, WesternCase-Control StudiesCD4-Positive T-LymphocytesCell DifferentiationCytokinesEnzyme-Linked Immunosorbent AssayFemaleFlow CytometryHLA-B27 AntigenHumansMaleCytokinesHLA-B27 AntigenKIR3DL2 protein, humanReceptors, Antigen, T-CellReceptors, KIR3DL2

Identifiers

PMID26841353
PMCPMC4855641
OpenAlexW2417954352

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.