Evidence map›Paper›PMID 26815131›Full record

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

Next-Generation Sequencing Reveals Restriction and Clonotypic Expansion of Treg Cells in Juvenile Idiopathic Arthritis.

Lauren A Henderson, Stefano Volpi, Francesco Frugoni, Erin Janssen, Susan Kim, Robert P Sundel, Fatma Dedeoglu, Mindy S Lo, Melissa M Hazen, Mary Beth Son and 9 more

Open access · greenAbstract readComparative Study
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 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
3.3field-weighted citation impact, top 8% 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

43 citing papers in PubMed, 61 citations in OpenAlex.

  1. Trial
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  9. The 'TNature reviews. Rheumatology · 2025
    Review
  10. Article
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  12. Review
  13. Article
  14. Review
  15. Article
  16. Review
  17. Article
  18. Juvenile idiopathic arthritis.Nature reviews. Disease primers · 2022
    Review
  19. NovelFrontiers in pediatrics · 2022
    Article
  20. Article
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

19 authors at 6 institutions in 1 country.

Lauren A HendersonBoston Children's Hospital, Boston, Massachusetts.
Stefano VolpiBoston Children's Hospital, Boston, Massachusetts.
Francesco FrugoniBoston Children's Hospital, Boston, Massachusetts.
Erin JanssenBoston Children's Hospital, Boston, Massachusetts.
Susan KimBoston Children's Hospital, Boston, Massachusetts.
Robert P SundelBoston Children's Hospital, Boston, Massachusetts.
Fatma DedeogluBoston Children's Hospital, Boston, Massachusetts.
Mindy S LoBoston Children's Hospital, Boston, Massachusetts.
Melissa M HazenBoston Children's Hospital, Boston, Massachusetts.
Mary Beth SonBoston Children's Hospital, Boston, Massachusetts.
Ronald MathieuBoston Children's Hospital, Boston, Massachusetts.
David ZurakowskiBoston Children's Hospital, Boston, Massachusetts.
Neng YuAmerican Red Cross Blood Services-East Division, New England HLA Services, Dedham, Massachusetts.
Tatiana LebedevaAmerican Red Cross Blood Services-East Division, New England HLA Services, Dedham, Massachusetts.
Robert C FuhlbriggeBoston Children's Hospital and Brigham and Women's Hospital, Boston, Massachusetts.
Jolan E WalterBoston Children's Hospital and Massachusetts General Hospital for Children, Boston, Massachusetts.
Yu Nee LeeBoston Children's Hospital, Boston, Massachusetts.
Peter A NigrovicBoston Children's Hospital and Brigham and Women's Hospital, Boston, Massachusetts.
Luigi D NotarangeloBoston Children's Hospital, Harvard Medical School, and Harvard Stem Cell Institute, Boston, Massachusetts.
Boston Children's Hospital · USBoston Children's Museum · USAmerican Red Cross · USBrigham and Women's Hospital · USHarvard Stem Cell Institute · USMassachusetts General Hospital · US

Funding

MOLECULAR BASIS OF ALLERGIC AND IMMUNOLOGIC DISEASET32AI007512 · NIAID · CHILDREN'S HOSPITAL BOSTON · PI Janet Chou, Peter A Nigrovic · 1996 to 2026
$13.1M
Ly6 family members in neutrophil biologyR01AR065538 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI NIGROVIC, PETER A · 2014 to 2024
$4.0M
NIAID NIH HHS T32 AI007512NIAMS NIH HHS L40 AR065238NIAMS NIH HHS R01 AR065538
6 · The paper itself

Abstract

objectiveTreg cell-mediated suppression of Teff cells is impaired in juvenile idiopathic arthritis (JIA); however, the basis for this dysfunction is incompletely understood. Animal models of autoimmunity and immunodeficiency demonstrate that a diverse Treg cell repertoire is essential to maintain Treg cell function. The present study was undertaken to investigate the Treg and Teff cell repertoires in JIA.

methodsTreg cells (CD4+CD25+CD127(low) ) and Teff cells (CD4+CD25-) were isolated from peripheral blood and synovial fluid obtained from JIA patients, healthy controls, and children with Lyme arthritis. Treg cell function was measured in suppressive assays. The T cell receptor β chain (TRB) was amplified by multiplex polymerase chain reaction and next-generation sequencing was performed, with amplicons sequenced using an Illumina HiSeq platform. Data were analyzed using ImmunoSEQ, International ImMunoGeneTics system, and the Immunoglobulin Analysis Tools.

resultsCompared to findings in controls, the JIA peripheral blood Treg cell repertoire was restricted, and clonotypic expansions were found in both blood and synovial fluid Treg cells. Skewed usage and pairing of TRB variable and joining genes, including overuse of gene segments that have been associated with other autoimmune conditions, was observed. JIA patients shared a substantial portion of synovial fluid Treg cell clonotypes that were private to JIA and not identified in Lyme arthritis.

conclusionWe identified restriction and clonotypic expansions in the JIA Treg cell repertoire with sharing of Treg cell clonotypes across patients. These findings suggest that abnormalities in the Treg cell repertoire, possibly engendered by shared antigenic triggers, may contribute to disease pathogenesis in JIA.

Indexed as

AdolescentArthritis, JuvenileCells, CulturedChildChild, PreschoolCross-Sectional StudiesFemaleHumansMaleSynovial FluidT-Lymphocytes, RegulatoryT-Lymphocyte Subsets

Identifiers

PMID26815131
PMCPMC5398095
OpenAlexW2331514369

What OpenQuestion holds

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LicenceTDM
Read underepoch 390

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.