Effects of different B-cell-depleting strategies on the lymphatic tissue

Tur C, Eckstein M, Bucci L, Auth J, Bergmann C, Rauber S, Hagen M, Nöthling DM, Böltz S, Wirsching A, Tascilar K, Fagni F, Corte G, Rius Rigau AR, Qin Y, Garantziotis P, Taubmann J, Wacker J, Ramming A, D´Agostino MA, Rauch S, Hartmann A, Müller F, Mackensen A, Grieshaber Bouyer R, Schett G, Bozec A, Raimondo MG (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Annals of the Rheumatic Diseases BMJ Publishing Group

DOI: 10.1016/j.ard.2025.06.2120

Abstract

Objectives: To assess the efficacy of new protein-based B cell depletion with glyco-engineered anti-CD20 antibody obinutuzumab (OBI) and the CD19/CD3 T cell engager blinatumomab (BLI) in patients with autoimmune diseases (AIDs) in comparison to rituximab (RTX) and CD19 chimeric antigen receptor (CAR) T cell therapy. Methods: Sequential inguinal lymph node biopsies were taken before and after treatment with OBI-, BLI-, RTX- and CD19-CAR T cells in patients with AID. CD19+ and CD20+ B cells, plasma cells, T cells and macrophages were analysed by immunohistochemistry. Changes in follicular architecture (follicular dendritic cells, T follicular helper cells, proliferation) were also assessed. Results: Baseline and follow-up lymph node biopsies from 24 patients with AID (OBI, 4; BLI, 4; RTX, 4; CD19-CAR T cells, 12) were analysed. B cell depletion was confirmed in all CD19-CAR T cell-treated patients but only in 1 (OBI) out of 12 protein-based B cell-treated patients. Likewise, follicular architecture was disrupted in all CD19-CAR T cell-treated patients but only in 1 (OBI) out of 12 protein-based B cell-treated patients. B cell depletion efficacy in the lymph nodes was 100% for CD19-CAR T cells, 92% for OBI, 86% for RTX and 69% for BLI. Plasma cells were reduced but not depleted in all treatment approaches. CD3+ T cells and CD68+ macrophages remained unaffected. Peripheral blood B cell depletion occurred in all but 1 BLI-treated patient. B cell depletion was associated with stable drug-free remission, whereas a reduction in B cell numbers without depletion required retreatment with immunomodulatory drugs. Conclusions: Protein-based B cell depletion reduces but usually does not deplete B cells in lymph nodes leaving the follicular architecture intact and being associated with disease recurrence.

Authors with CRIS profile

Carlo Tur Department of Medicine 3 – Rheumatology and Immunology Markus Eckstein Institute of Pathology Laura Bucci Department of Medicine 3 – Rheumatology and Immunology Janina Auth Department of Medicine 3 – Rheumatology and Immunology Christina Bergmann Department of Medicine 3 – Rheumatology and Immunology Simon Rauber Department of Medicine 3 – Rheumatology and Immunology Melanie Hagen Department of Medicine 3 – Rheumatology and Immunology Danae-Mona Nöthling Lehrstuhl für Mikrobiologie und Infektionsimmunologie Sebastian Böltz Department of Medicine 3 – Rheumatology and Immunology Koray Tascilar Department of Medicine 3 – Rheumatology and Immunology Filippo Fagni Department of Medicine 3 – Rheumatology and Immunology Aleix Rius Rigau Department of Medicine 3 – Rheumatology and Immunology Panagiotis Garantziotis Department of Medicine 3 – Rheumatology and Immunology Jule Bachl Department of Medicine 3 – Rheumatology and Immunology Andreas Ramming Medizinische Fakultät Sebastian Rauch Institute of Pathology Arndt Hartmann Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie Fabian Müller Department of Medicine 5 – Haematology and Oncology Andreas Mackensen Lehrstuhl für Innere Medizin V Ricardo Grieshaber Bouyer Professur für Klinische Systemimmunologie Georg Schett Lehrstuhl für Innere Medizin III Aline Bozec Maria Gabriella Raimondo Department of Medicine 3 – Rheumatology and Immunology

Involved external institutions

Fondazione Policlinico Universitario Agostino Gemelli IRCCS IT Italy (IT)

How to cite

APA:

Tur, C., Eckstein, M., Bucci, L., Auth, J., Bergmann, C., Rauber, S.,... Raimondo, M.G. (2025). Effects of different B-cell-depleting strategies on the lymphatic tissue. Annals of the Rheumatic Diseases. https://doi.org/10.1016/j.ard.2025.06.2120

MLA:

Tur, Carlo, et al. "Effects of different B-cell-depleting strategies on the lymphatic tissue." Annals of the Rheumatic Diseases (2025).

BibTeX: Download