RT Journal Article
SR Electronic
T1 Defects in B-lymphopoiesis and B-cell maturation underlie prolonged B-cell depletion in ANCA-associated vasculitis
JF Annals of the Rheumatic Diseases
JO Ann Rheum Dis
FD BMJ Publishing Group Ltd and European League Against Rheumatism
SP 1536
OP 1548
DO 10.1136/ard-2024-225587
VO 83
IS 11
A1 Thiel, Jens
A1 Schmidt, Franziska M
A1 Lorenzetti, Raquel
A1 Troilo, Arianna
A1 Janowska, Iga
A1 Nießen, Lena
A1 Pfeiffer, Sophie
A1 Staniek, Julian
A1 Benassini, Bruno
A1 Bott, Marei-Theresa
A1 Korzhenevich, Jakov
A1 Konstantinidis, Lukas
A1 Burgbacher, Frank
A1 Dufner, Ann-Katrin
A1 Frede, Natalie
A1 Voll, Reinhard E
A1 Stuchly, Jan
A1 Bakardjieva, Marina
A1 Kalina, Tomas
A1 Smulski, Cristian Roberto
A1 Venhoff, Nils
A1 Rizzi, Marta
YR 2024
UL http://ard.bmj.com/content/83/11/1536.abstract
AB 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.Data are available on reasonable request.