Evidence map›Paper›PMID 41591822›Full record

Observational studyKidney3602026

IgA-Producing B Cells Exert Regulatory Function through Granzyme B in Kidney Allograft Tolerance.

Laureline Berthelot, Nicolas Degauque, Laura Cappelier, Nicolas Sailliet, Camille Mathé, François Brinas, Amandine Dupuy, Léo Boussamet, Gaelle Tilly, Luc Colas and 8 more

Registry-linked trialAbstract readMulticenter StudyObservational Study
In one paragraph

Observational study in Kidney360, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02900040 (The French DIVAT), which is not on this map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–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.

NCT02900040 recruitingnot on this map

The French DIVAT: a Clinical Database Associated With a Biological Banking Accessible to Initiate Epidemiological and Translational Collaborative Researches in Kidney Transplantation

Typeobservational_patient_registrySponsorNantes University HospitalRan1994 to 2050Enrolled30,000ConditionsKidney TransplantationArmskidney transplantation
3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

18 authors.

Laureline BerthelotInserm, Nantes Université, CHU de Nantes, Center for Research in Transplantation and Translational Immunology CR2TI, UMR 1064, ITUN, Nantes, France.ORCID 0000-0002-9306-9247
Nicolas DegauqueInserm, Nantes Université, CHU de Nantes, Center for Research in Transplantation and Translational Immunology CR2TI, UMR 1064, ITUN, Nantes, France.ORCID 0000-0003-2990-3513
Laura CappelierInserm, Nantes Université, CHU de Nantes, Center for Research in Transplantation and Translational Immunology CR2TI, UMR 1064, ITUN, Nantes, France.
Nicolas SaillietInserm, Nantes Université, CHU de Nantes, Center for Research in Transplantation and Translational Immunology CR2TI, UMR 1064, ITUN, Nantes, France.ORCID 0000-0002-0232-1663
Camille MathéInserm, Nantes Université, CHU de Nantes, Center for Research in Transplantation and Translational Immunology CR2TI, UMR 1064, ITUN, Nantes, France.ORCID 0000-0001-5432-6741
François BrinasInserm, Nantes Université, CHU de Nantes, Center for Research in Transplantation and Translational Immunology CR2TI, UMR 1064, ITUN, Nantes, France.
Amandine DupuyInserm, Nantes Université, CHU de Nantes, Center for Research in Transplantation and Translational Immunology CR2TI, UMR 1064, ITUN, Nantes, France.
Léo BoussametInserm, Nantes Université, CHU de Nantes, Center for Research in Transplantation and Translational Immunology CR2TI, UMR 1064, ITUN, Nantes, France.ORCID 0000-0001-8437-666
Gaelle TillyInserm, Nantes Université, CHU de Nantes, Center for Research in Transplantation and Translational Immunology CR2TI, UMR 1064, ITUN, Nantes, France.
Luc ColasInserm, Nantes Université, CHU de Nantes, Center for Research in Transplantation and Translational Immunology CR2TI, UMR 1064, ITUN, Nantes, France.ORCID 0000-0001-8226-4250
Mélanie ChesneauInserm, Nantes Université, CHU de Nantes, Center for Research in Transplantation and Translational Immunology CR2TI, UMR 1064, ITUN, Nantes, France.
Clarisse KerleauInserm, Nantes Université, CHU de Nantes, Center for Research in Transplantation and Translational Immunology CR2TI, UMR 1064, ITUN, Nantes, France.ORCID 0000-0002-1487-5743
Magali GiralInserm, Nantes Université, CHU de Nantes, Center for Research in Transplantation and Translational Immunology CR2TI, UMR 1064, ITUN, Nantes, France.ORCID 0000-0001-7641-1592
Richard DangerInserm, Nantes Université, CHU de Nantes, Center for Research in Transplantation and Translational Immunology CR2TI, UMR 1064, ITUN, Nantes, France.ORCID 0000-0002-5058-795
Hoa Le MaiInserm, Nantes Université, CHU de Nantes, Center for Research in Transplantation and Translational Immunology CR2TI, UMR 1064, ITUN, Nantes, France.ORCID 0000-0003-2099-4420
Nataliya YeremenkoInserm, Nantes Université, CHU de Nantes, Center for Research in Transplantation and Translational Immunology CR2TI, UMR 1064, ITUN, Nantes, France.
Sophie BrouardInserm, Nantes Université, CHU de Nantes, Center for Research in Transplantation and Translational Immunology CR2TI, UMR 1064, ITUN, Nantes, France.
Divat Consortium

Funding

Agence Nationale de la Recherche ANR-22-CE17-0055-01Conseil Régional des Pays de la Loire LOIRE-TIMESERA PerMed AGORA ERAPERMED2021-086KTD-INNOV RC18_0013_01Labex IGO ANR-11-LABX-0016-01
6 · The paper itself

Abstract

key pointsTolerant patients of kidney graft exhibit higher IgA production than other kidney transplanted patients without modification for IgG. IgA-expressing B cells from tolerant patients expressed granzyme B and exert regulatory functions through granzyme B production.

backgroundTolerant kidney transplant recipients without immunosuppression have a high frequency of circulating granzyme B (GZMB)-expressing regulatory B cells (Breg). Because the precursors of these Bregs remain unknown and IgA-secreting B cells have been shown to have regulatory properties in different situations, we investigated the association between IgA- and GZMB-expressing B cells in a case-control study.

methodsForty-five healthy volunteers and 31 kidney transplant recipients with either stable graft function under immunosuppression ( n =10), antibody-mediated rejection ( n =7), or tolerant patients (TOL; n =14) were included. Serum immunoglobulin concentrations as glycosylation were measured by ELISA; forms of IgA were examined by Western blot. Bregs were analyzed by single-cell RNA sequencing and multiparameter spectral flow cytometry. Their function was assessed in cocultured with T cells.

resultsSerum IgA concentration was elevated in TOL compared with other transplanted patients, especially the noninflammatory IgA1 subclass, without changes in IgA size or glycosylation. Single-cell transcriptomic analysis revealed higher IgA gene expression in GZMB expressing B cells and conversely higher GZMB gene expression in IgA-expressing B cells. Phenotyping analysis by spectral multiparameter flow cytometry showed that IgA+ B cells were memory B cells, and that IgA+ B cells from TOL tended to express more GZMB compared with antibody-mediated rejection patients. In functional assays, IgA+ B cells exhibited high regulatory functions that were partially prevented by the presence of GZMB inhibitor.

conclusionsThese data show a strong association between IgA+ and GZMB+ Bregs, particularly in tolerant kidney transplant recipients with higher GZMB and IgA expression and greater suppressive properties. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: NCT02900040 .

Indexed as

B-Lymphocytes, RegulatoryGraft RejectionGranzymesImmunoglobulin AKidney TransplantationTransplantation ToleranceAdultAllograftsCase-Control StudiesFemaleHumansMaleMiddle AgedGranzymesGZMB protein, humanImmunoglobulin Achronic allograft rejectionIgAimmunologykidneyregulationtolerancetransplantationtransplant outcomes

Identifiers

PMID41591822
PMCPMC13337167

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

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.