Autoreactive Plasmablasts After B Cell Depletion With Rituximab and Relapses in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis

Objective Autoreactive B cells are responsible for antineutrophil cytoplasmic antibody (ANCA) production in ANCA‐associated vasculitis (AAV). Rituximab (RTX) depletes circulating B cells, including autoreactive B cells. We aimed to evaluate changes and associations with relapse of the circulating au...

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Published in:Arthritis & rheumatology (Hoboken, N.J.) N.J.), 2023-05, Vol.75 (5), p.736-747
Main Authors: Berti, Alvise, Hillion, Sophie, Konig, Maximilian F., Moura, Marta Casal, Hummel, Amber M., Carmona, Eva, Peikert, Tobias, Fervenza, Fernando C., Kallenberg, Cees G.M., Langford, Carol A., Merkel, Peter A., Monach, Paul A., Seo, Philip, Spiera, Robert F., Brunetta, Paul, St. Clair, E. William, Harris, Kristina M., Stone, John H., Grandi, Guido, Pers, Jacques‐Olivier, Specks, Ulrich, Cornec, Divi
Format: Article
Language:English
Subjects:
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Antibodies
Antibodies, Antineutrophil Cytoplasmic
Antineutrophil cytoplasmic antibodies
Blood
Depletion
Ecology, environment
Flow cytometry
Health
Humans
Leukocytes, Mononuclear
Life Sciences
Lymphocytes B
Myeloblastin
Patients
Peripheral blood mononuclear cells
Prospective Studies
Proteinase
Proteinase 3
Recurrence
Remission
Rituximab
Rituximab - therapeutic use
Vasculitis
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Summary:Objective Autoreactive B cells are responsible for antineutrophil cytoplasmic antibody (ANCA) production in ANCA‐associated vasculitis (AAV). Rituximab (RTX) depletes circulating B cells, including autoreactive B cells. We aimed to evaluate changes and associations with relapse of the circulating autoreactive B cell pool following therapeutic B cell depletion in AAV. Methods Sequential flow cytometry was performed on 148 samples of peripheral blood mononuclear cells from 23 patients with proteinase 3 (PR3)–ANCA–positive AAV who were treated with RTX for remission induction and monitored after stopping therapy during long‐term follow‐up in a prospective clinical trial. PR3 was used as a ligand to target autoreactive PR3‐specific (PR3+) B cells. B cell recurrence was considered as the first blood sample with ≥10 B cells/μl after RTX treatment. Results At B cell recurrence, PR3+ B cell frequency among B cells was higher than baseline (P 
ISSN:2326-5191
2326-5205
2326-5205
2326-5191
DOI:10.1002/art.42388