Evidence map›Paper›PMID 32963045›Full record

ArticleAnnals of the rheumatic diseases2020

Unique expansion of IL-21+ Tfh and Tph cells under control of ICOS identifies Sjögren's syndrome with ectopic germinal centres and MALT lymphoma.

Elena Pontarini, William James Murray-Brown, Cristina Croia, Davide Lucchesi, James Conway, Felice Rivellese, Liliane Fossati-Jimack, Elisa Astorri, Edoardo Prediletto, Elisa Corsiero and 19 more

Open access · hybridAbstract read
In one paragraph

Article in Annals of the rheumatic diseases, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
106citing papers in PubMed, 2 pooled it
11.3field-weighted citation impact, top 1% 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

106 citing papers in PubMed, 2 syntheses or guidelines pooled it, 177 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Review
  5. Regulation of Tph cell differentiation via farnesoid X receptor of dendritic cells in inflammatory bowel disease.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
    Article
  6. Review
  7. Article
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  9. Proceedings of the 2Mediterranean journal of rheumatology · 2026
    Article
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  12. The CNS Meninges and the Synovial Joint: Parallel Immunological Structures in Autoimmune Disease.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026
    Review
  13. Article
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  16. Article
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46 more citing papers are in PubMed but not listed here.

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

29 authors at 10 institutions in 6 countries.

Elena Pontarini *Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, London, England, UK.ORCID 0000-0003-0439-0344
William James Murray-Brown *Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, London, England, UK.ORCID 0000-0001-9673-8787
Cristina Croia *Immuno-Allergology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.ORCID 0000-0003-3871-9427
Davide LucchesiCentre for Experimental Medicine and Rheumatology, William Harvey Research Institute, London, England, UK.ORCID 0000-0002-8019-556X
James ConwayOncology R&D, Astrazeneca, Gaithersburg, Maryland, USA.ORCID 0000-0002-1725-8193
Felice RivelleseCentre for Experimental Medicine and Rheumatology, William Harvey Research Institute, London, England, UK.ORCID 0000-0002-6759-7521
Liliane Fossati-JimackCentre for Experimental Medicine and Rheumatology, William Harvey Research Institute, London, England, UK.ORCID 0000-0003-3757-3999
Elisa AstorriCentre for Experimental Medicine and Rheumatology, William Harvey Research Institute, London, England, UK.
Edoardo PredilettoCentre for Experimental Medicine and Rheumatology, William Harvey Research Institute, London, England, UK.ORCID 0000-0001-6830-0614
Elisa CorsieroCentre for Experimental Medicine and Rheumatology, William Harvey Research Institute, London, England, UK.ORCID 0000-0003-2092-6778
Francesca Romana DelvecchioCentre for Experimental Medicine and Rheumatology, William Harvey Research Institute, London, England, UK.ORCID 0000-0002-3661-1212
Rachel ColebyCentre for Experimental Medicine and Rheumatology, William Harvey Research Institute, London, England, UK.ORCID 0000-0002-2490-0199
Eva GelbhardtCentre for Experimental Medicine and Rheumatology, William Harvey Research Institute, London, England, UK.
Aurora BonoCentre for Experimental Medicine and Rheumatology, William Harvey Research Institute, London, England, UK.
Chiara BaldiniUniversity of Pisa, Rheumatology Unit, Pisa, PI, Italy.ORCID 0000-0002-4454-1824
Ilaria PuxedduImmuno-Allergology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.ORCID 0000-0001-7293-7933
Piero RuscittiDepartment of Clinical Sciences and Applied Biotechnology, University of L'Aquila, L'Aquila, Abruzzo, Italy.ORCID 0000-0003-3487-8551
Roberto GiacomelliDepartment of Clinical Sciences and Applied Biotechnology, University of L'Aquila, L'Aquila, Abruzzo, Italy.ORCID 0000-0003-0670-9638
Francesca BaroneRRG, Institute of Inflamation and Ageing, University of Birmingham, Birmingham, UK, UK.ORCID 0000-0002-5287-9614
Benjamin FisherRRG, Institute of Inflamation and Ageing, University of Birmingham, Birmingham, UK, UK.ORCID 0000-0003-4631-549X
Simon J BowmanNIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.ORCID 0000-0001-9880-9948
Serena ColafrancescoDipartimento di Medicina Interna e Specilità Mediche, UOC Reumatologia, Universita degli Studi di Roma La Sapienza Facolta di Medicina e Odontoiatria, Roma, Lazio, Italy.ORCID 0000-0001-7802-1192
Roberta PrioriDipartimento di Medicina Interna e Specilità Mediche, UOC Reumatologia, Universita degli Studi di Roma La Sapienza Facolta di Medicina e Odontoiatria, Roma, Lazio, Italy.ORCID 0000-0002-6695-1445
Nurhan SutcliffeRheumatology, Barts Health NHS Trust, London, London, UK.ORCID 0000-0002-8150-6446
Stephen ChallacombeOral Medicine, KCL Dental Institute, London, UK.
Gianluca CarlessoEarly ICA Discovery, Early Oncology R&D, AstraZeneca, Gaithersburg, Maryland, USA.ORCID 0000-0002-9592-3267
Anwar TappuniInstitute of Dentistry, Barts and The London School of Medicine and Dentistry, London, London, UK.ORCID 0000-0002-5370-2423
Costantino PitzalisCentre for Experimental Medicine and Rheumatology, William Harvey Research Institute, London, England, UK.ORCID 0000-0003-1326-5051
Michele BombardieriCentre for Experimental Medicine and Rheumatology, William Harvey Research Institute, London, England, UK m.bombardieri@qmul.ac.uk.ORCID 0000-0002-3878-5216
Centre of Experimental Medicine of the Slovak Academy of Sciences · SKUniversity Hospitals Birmingham NHS Foundation Trust · GBUniversity of Pisa · ITSapienza University of Rome · ITUniversity of L'Aquila · ITAstraZeneca (Brazil) · BRAstraZeneca (United States) · USBarts Health NHS Trust · GBEastman Dental Hospital · GBQueen Mary University of London · GB

Funding

Cancer Research UK 26687Department of Health TRF-2018-11-ST2-002Medical Research Council MR/K020250/1Medical Research Council MR/N003063/1Versus Arthritis 20089Versus Arthritis 21268Versus Arthritis 21753Wellcome Trust
6 · The paper itself

Abstract

objectivesTo explore the relevance of T-follicular-helper (Tfh) and pathogenic peripheral-helper T-cells (Tph) in promoting ectopic lymphoid structures (ELS) and B-cell mucosa-associated lymphoid tissue (MALT) lymphomas (MALT-L) in Sjögren's syndrome (SS) patients.

methodsSalivary gland (SG) biopsies with matched peripheral blood were collected from four centres across the European Union. Transcriptomic (microarray and quantitative PCR) analysis, FACS T-cell immunophenotyping with intracellular cytokine detection, multicolor immune-fluorescence microscopy and

resultsTranscriptomic analysis in SG identified Tfh-signature, interleukin-21 (IL-21) and the inducible T-cell co-stimulator (ICOS) costimulatory pathway as the most upregulated genes in ELS+SS patients, with parotid MALT-L displaying a 400-folds increase in IL-21 mRNA. Peripheral CD4

conclusionsOverall, these findings highlight Tfh and Tph-cells, IL-21 and the ICOS costimulatory pathway as key pathogenic players in SS immunopathology and exploitable therapeutic targets in SS.

Indexed as

Germinal CenterAdultAgedChoristomaFemaleHumansImmunophenotypingInducible T-Cell Co-Stimulator ProteinInterleukin-21InterleukinsLymphoma, B-Cell, Marginal ZoneMaleMiddle AgedSalivary Gland DiseasesSjogren's SyndromeT Follicular Helper CellsICOS protein, humanInducible T-Cell Co-Stimulator ProteinInterleukin-21Interleukinsautoimmune diseasescytokinessjogren's syndromet-lymphocyte subsets

Identifiers

PMID32963045
PMCPMC7677495
OpenAlexW3089041431

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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.