Evidence map›Paper›PMID 31033594›Full record

ArticleClinical and translational gastroenterology2019

Activated T-Follicular Helper 2 Cells Are Associated With Disease Activity in IgG4-Related Sclerosing Cholangitis and Pancreatitis.

Tamsin Cargill, Mateusz Makuch, Ross Sadler, Laura C Lighaam, Rory Peters, Marieke van Ham, Paul Klenerman, Adrian Bateman, Theo Rispens, Eleanor Barnes and 1 more

Erratum issuedOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical and translational gastroenterology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
5.3field-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

27 citing papers in PubMed, 51 citations in OpenAlex.

  1. Review
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  9. Implication of allergy and atopy in IgG4-related disease.The World Allergy Organization journal · 2023
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  18. IgG4 as a Biomarker in Graves' Orbitopathy.Mediators of inflammation · 2021
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  20. Observational
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 7 institutions in 2 countries.

Tamsin CargillPeter Medawar Building for Pathogen Research and Oxford NIHR BRC, Nuffield Department of Medicine, University of Oxford, South Parks Road, Oxford, UK.
Mateusz MakuchSanquin, Division Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
Ross SadlerDepartment of Immunology, Churchill Hospital, Oxford University Hospitals NHS Trust, Oxford, UK.
Laura C LighaamSanquin, Division Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
Rory PetersPeter Medawar Building for Pathogen Research and Oxford NIHR BRC, Nuffield Department of Medicine, University of Oxford, South Parks Road, Oxford, UK.
Marieke van HamSanquin, Division Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
Paul KlenermanPeter Medawar Building for Pathogen Research and Oxford NIHR BRC, Nuffield Department of Medicine, University of Oxford, South Parks Road, Oxford, UK.
Adrian BatemanDepartment of Pathology, Southampton General Hospital, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
Theo RispensSanquin, Division Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
Eleanor BarnesPeter Medawar Building for Pathogen Research and Oxford NIHR BRC, Nuffield Department of Medicine, University of Oxford, South Parks Road, Oxford, UK.
Emma L CulverPeter Medawar Building for Pathogen Research and Oxford NIHR BRC, Nuffield Department of Medicine, University of Oxford, South Parks Road, Oxford, UK.
Medawar Building for Pathogen Research · GBSanquin · NLUniversity of Oxford · GBAcademic Medical Center · NLJohn Radcliffe Hospital · GBOxford University Hospitals NHS Trust · GBUniversity of Amsterdam · NL

Funding

Department of HealthMedical Research CouncilWellcome Trust 091663MAWellcome Trust 095160/Z10/ZWellcome Trust 109965/Z/15/ZWellcome Trust 211042/Z/18/Z
6 · The paper itself

Abstract

objectivesImmunoglobulin G4-related sclerosing cholangitis (IgG4-SC) and autoimmune pancreatitis (AIP) are characterized by an abundance of circulating and tissue IgG4-positive plasma cells. T-follicular helper (Tfh) cells are necessary for B-cell differentiation into plasma cells. We aimed at elucidating the presence and phenotype of Tfh cells and their relationship with disease activity in IgG4-SC/AIP.

methodsCirculating Tfh-cell subsets were characterized by multiparametric flow cytometry in IgG4-SC/AIP (n = 18), disease controls with primary sclerosing cholangitis (n = 8), and healthy controls (HCs, n = 9). Tissue Tfh cells were characterized in IgG4-SC/AIP (n = 12) and disease control (n = 10) specimens. Activated PD1+ Tfh cells were cocultured with CD27+ memory B cells to assess their capacity to support B-cell differentiation. Disease activity was assessed using the IgG4-responder index and clinical parameters.

resultsActivated circulating PD-1+CXCR5+ Tfh cells were expanded in active vs inactive IgG4-SC/AIP, primary sclerosing cholangitis, and HC (P < 0.01), with enhanced PD-1 expression on all Tfh-cell subsets (Tfh1, P = 0.003; Tfh2, P = 0.0006; Th17, P = 0.003). Expansion of CD27+CD38+CD19lo plasmablasts in active disease vs HC (P = 0.01) correlated with the PD-1+ Tfh2 subset (r = 0.69, P = 0.03). Increased IL-4 and IL-21 cytokine production from stimulated cells of IgG4-SC/AIP, important in IgG4 class switch and proliferation, correlated with PD-1+ Tfh2 (r = 0.89, P = 0.02) and PD-1+ Tfh17 (r = 0.83, P = 0.03) subsets. Coculture of PD1+ Tfh with CD27+ B cells induced higher IgG4 expression than with PD1- Tfh (P = 0.008). PD-1+ Tfh2 cells were strongly associated with clinical markers of disease activity: sIgG4 (r = 0.70, P = 0.002), sIgE (r = 0.66, P = 0.006), and IgG4-responder index (r = 0.60, P = 0.006). Activated CXCR5+ Tfh cells homed to lymphoid follicles in IgG4-SC/AIP tissues.

conclusionsCirculating and tissue-activated Tfh cells are expanded in IgG4-SC/AIP, correlate with disease activity, and can drive class switch and proliferation of IgG4-committed B cells. PD1+ Tfh2 cells may be a biomarker of active disease and a potential target for immunotherapy.

Indexed as

AdultAgedAged, 80 and overBiliary TractBiopsyB-LymphocytesCells, CulturedCell SeparationCholangitis, SclerosingCoculture TechniquesFemaleFlow CytometryHumansImmunoglobulin GLymphocyte ActivationMaleImmunoglobulin G

Identifiers

PMID31033594
PMCPMC6602789
OpenAlexW2942673276

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.