dc.contributor.author | Thiel, Jens | |
dc.contributor.author | Schmidt, Franziska M | |
dc.contributor.author | Lorenzetti, Raquel | |
dc.contributor.author | Troilo, Arianna | |
dc.contributor.author | Janowska, Iga | |
dc.contributor.author | Nießen, Lena | |
dc.contributor.author | Pfeiffer, Sophie | |
dc.contributor.author | Staniek, Julian | |
dc.contributor.author | Benassini, Bruno | |
dc.contributor.author | Bott, Marei-Theresa | |
dc.contributor.author | Korzhenevich, Jakov | |
dc.contributor.author | Konstantinidis, Lukas | |
dc.contributor.author | Burgbacher, Frank | |
dc.contributor.author | Dufner, Ann-Katrin | |
dc.contributor.author | Frede, Natalie | |
dc.contributor.author | Voll, Reinhard E | |
dc.contributor.author | Stuchlý, Jan | |
dc.contributor.author | Bakardjieva, Marina | |
dc.contributor.author | Kalina, Tomáš | |
dc.contributor.author | Smulski, Cristian Roberto | |
dc.contributor.author | Venhoff, Nils | |
dc.contributor.author | Rizzi, Marta | |
dc.date.accessioned | 2024-10-03T08:15:45Z | |
dc.date.available | 2024-10-03T08:15:45Z | |
dc.date.issued | 2024 | |
dc.identifier.uri | https://hdl.handle.net/20.500.14178/2642 | |
dc.description.abstract | OBJECTIVES: 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.iso | en | |
dc.relation.url | https://doi.org/10.1136/ard-2024-225587 | |
dc.rights | Creative Commons Uveďte původ-Neužívejte dílo komerčně 4.0 International | cs |
dc.rights | Creative Commons Attribution-NonCommercial 4.0 International | en |
dc.title | Defects in B-lymphopoiesis and B-cell maturation underlie prolonged B-cell depletion in ANCA-associated vasculitis | en |
dcterms.accessRights | openAccess | |
dcterms.license | https://creativecommons.org/licenses/by-nc/4.0/legalcode | |
dc.date.updated | 2025-01-21T17:11:16Z | |
dc.subject.keyword | B-lymphocytes | en |
dc.subject.keyword | rituximab | en |
dc.subject.keyword | vasculitis | en |
dc.identifier.eissn | 1468-2060 | |
dc.relation.fundingReference | info:eu-repo/grantAgreement/MSM//LX22NPO5102 | |
dc.relation.fundingReference | info:eu-repo/grantAgreement/GA0/GA/GA23-05561S | |
dc.relation.fundingReference | info:eu-repo/grantAgreement/FN/I-FN/I-FNM | |
dc.date.embargoStartDate | 2025-01-21 | |
dc.type.obd | 73 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | |
dc.identifier.doi | 10.1136/ard-2024-225587 | |
dc.identifier.utWos | 001241837200001 | |
dc.identifier.eidScopus | 2-s2.0-85196318041 | |
dc.identifier.obd | 648832 | |
dc.identifier.pubmed | 38851295 | |
dc.subject.rivPrimary | 30000::30200::30205 | |
dc.subject.rivSecondary | 30000::30200::30204 | |
dcterms.isPartOf.name | Annals of the Rheumatic Diseases | |
dcterms.isPartOf.issn | 0003-4967 | |
dcterms.isPartOf.journalYear | 2024 | |
dcterms.isPartOf.journalVolume | 83 | |
dcterms.isPartOf.journalIssue | 11 | |
uk.faculty.primaryId | 109 | |
uk.faculty.primaryName | 2. lékařská fakulta | cs |
uk.faculty.primaryName | Second Faculty of Medicine | en |
uk.faculty.secondaryId | 52 | |
uk.faculty.secondaryName | Fakultní nemocnice v Motole | cs |
uk.faculty.secondaryName | Motol University Hospital | en |
uk.department.primaryId | 109 | |
uk.department.primaryName | 2. lékařská fakulta | cs |
uk.department.primaryName | Second Faculty of Medicine | en |
uk.department.secondaryId | 1675 | |
uk.department.secondaryId | 100010692507 | |
uk.department.secondaryName | Klinika dětské hematologie a onkologie | cs |
uk.department.secondaryName | Klinika dětské hematologie a onkologie | en |
uk.department.secondaryName | Klinika dětské hematologie a onkologie 2. LF UK a FN Motol | cs |
uk.department.secondaryName | Department of Paediatric Haematology and Oncology, 2nd Faculty of Medicine and Motol University Hos | en |
dc.description.pageRange | 1536-1548 | |
dc.type.obdHierarchyCs | ČLÁNEK V ČASOPISU::článek v časopisu::původní článek | cs |
dc.type.obdHierarchyEn | JOURNAL ARTICLE::journal article::original article | en |
dc.type.obdHierarchyCode | 73::152::206 | en |
uk.displayTitle | Defects in B-lymphopoiesis and B-cell maturation underlie prolonged B-cell depletion in ANCA-associated vasculitis | en |