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Defects in B-lymphopoiesis and B-cell maturation underlie prolonged B-cell depletion in ANCA-associated vasculitis

dc.contributor.authorThiel, Jens
dc.contributor.authorSchmidt, Franziska M
dc.contributor.authorLorenzetti, Raquel
dc.contributor.authorTroilo, Arianna
dc.contributor.authorJanowska, Iga
dc.contributor.authorNießen, Lena
dc.contributor.authorPfeiffer, Sophie
dc.contributor.authorStaniek, Julian
dc.contributor.authorBenassini, Bruno
dc.contributor.authorBott, Marei-Theresa
dc.contributor.authorKorzhenevich, Jakov
dc.contributor.authorKonstantinidis, Lukas
dc.contributor.authorBurgbacher, Frank
dc.contributor.authorDufner, Ann-Katrin
dc.contributor.authorFrede, Natalie
dc.contributor.authorVoll, Reinhard E
dc.contributor.authorStuchlý, Jan
dc.contributor.authorBakardjieva, Marina
dc.contributor.authorKalina, Tomáš
dc.contributor.authorSmulski, Cristian Roberto
dc.contributor.authorVenhoff, Nils
dc.contributor.authorRizzi, Marta
dc.date.accessioned2024-10-03T08:15:45Z
dc.date.available2024-10-03T08:15:45Z
dc.date.issued2024
dc.identifier.urihttps://hdl.handle.net/20.500.14178/2642
dc.description.abstractOBJECTIVES: B-cell depletion time after rituximab (RTX) treatment is prolonged in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) compared with other autoimmune diseases. We investigated central and peripheral B-cell development to identify the causes for the defect in B-cell reconstitution after RTX therapy. METHODS: We recruited 91 patients with AAV and performed deep phenotyping of the peripheral and bone marrow B-cell compartment by spectral flow and mass cytometry. B-cell development was studied by in vitro modelling and the role of BAFF receptor by quantitative PCR, western blot analysis and in vitro assays. RESULTS: Treatment-naïve patients with AAV showed low transitional B-cell numbers, suggesting impaired B-lymphopoiesis. We analysed bone marrow of treatment-naïve and RTX-treated patients with AAV and found reduced B-lymphoid precursors. In vitro modelling of B-lymphopoiesis from AAV haematopoietic stem cells showed intact, but slower and reduced immature B-cell development. In a subgroup of patients, after RTX treatment, the presence of transitional B cells did not translate in replenishment of naïve B cells, suggesting an impairment in peripheral B-cell maturation. We found low BAFF-receptor expression on B cells of RTX-treated patients with AAV, resulting in reduced survival in response to BAFF in vitro. CONCLUSIONS: Prolonged depletion of B cells in patients with AAV after RTX therapy indicates a B-cell defect that is unmasked by RTX treatment. Our data indicate that impaired bone marrow B-lymphopoiesis results in a delayed recovery of peripheral B cells that may be further aggravated by a survival defect of B cells. Our findings contribute to the understanding of AAV pathogenesis and may have clinical implications regarding RTX retreatment schedules and immunomonitoring after RTX therapy.en
dc.language.isoen
dc.relation.urlhttps://doi.org/10.1136/ard-2024-225587
dc.rightsCreative Commons Uveďte původ-Neužívejte dílo komerčně 4.0 Internationalcs
dc.rightsCreative Commons Attribution-NonCommercial 4.0 Internationalen
dc.titleDefects in B-lymphopoiesis and B-cell maturation underlie prolonged B-cell depletion in ANCA-associated vasculitisen
dcterms.accessRightsopenAccess
dcterms.licensehttps://creativecommons.org/licenses/by-nc/4.0/legalcode
dc.date.updated2025-01-21T17:11:16Z
dc.subject.keywordB-lymphocytesen
dc.subject.keywordrituximaben
dc.subject.keywordvasculitisen
dc.identifier.eissn1468-2060
dc.relation.fundingReferenceinfo:eu-repo/grantAgreement/MSM//LX22NPO5102
dc.relation.fundingReferenceinfo:eu-repo/grantAgreement/GA0/GA/GA23-05561S
dc.relation.fundingReferenceinfo:eu-repo/grantAgreement/FN/I-FN/I-FNM
dc.date.embargoStartDate2025-01-21
dc.type.obd73
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.identifier.doi10.1136/ard-2024-225587
dc.identifier.utWos001241837200001
dc.identifier.eidScopus2-s2.0-85196318041
dc.identifier.obd648832
dc.identifier.pubmed38851295
dc.subject.rivPrimary30000::30200::30205
dc.subject.rivSecondary30000::30200::30204
dcterms.isPartOf.nameAnnals of the Rheumatic Diseases
dcterms.isPartOf.issn0003-4967
dcterms.isPartOf.journalYear2024
dcterms.isPartOf.journalVolume83
dcterms.isPartOf.journalIssue11
uk.faculty.primaryId109
uk.faculty.primaryName2. lékařská fakultacs
uk.faculty.primaryNameSecond Faculty of Medicineen
uk.faculty.secondaryId52
uk.faculty.secondaryNameFakultní nemocnice v Motolecs
uk.faculty.secondaryNameMotol University Hospitalen
uk.department.primaryId109
uk.department.primaryName2. lékařská fakultacs
uk.department.primaryNameSecond Faculty of Medicineen
uk.department.secondaryId1675
uk.department.secondaryId100010692507
uk.department.secondaryNameKlinika dětské hematologie a onkologiecs
uk.department.secondaryNameKlinika dětské hematologie a onkologieen
uk.department.secondaryNameKlinika dětské hematologie a onkologie 2. LF UK a FN Motolcs
uk.department.secondaryNameDepartment of Paediatric Haematology and Oncology, 2nd Faculty of Medicine and Motol University Hosen
dc.description.pageRange1536-1548
dc.type.obdHierarchyCsČLÁNEK V ČASOPISU::článek v časopisu::původní článekcs
dc.type.obdHierarchyEnJOURNAL ARTICLE::journal article::original articleen
dc.type.obdHierarchyCode73::152::206en
uk.displayTitleDefects in B-lymphopoiesis and B-cell maturation underlie prolonged B-cell depletion in ANCA-associated vasculitisen


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