The why, what, who and when of B cell depletion in systemic lupus erythematosus: biological rationale, patient stratification and evolving therapeutic modalities

Wincup C, Gatto M, Scherlinger M, Schett G, Hagen M (2026)

Publication Type: Journal article, Review article

Publication year: 2026

Journal

Rheumatology Oxford University Press

Book Volume: 65

Article Number: keag416

Journal Issue: 8

DOI: 10.1093/rheumatology/keag416

Abstract

Systemic lupus erythematosus (SLE) is driven by interconnected immune circuits in which B cells function as antigen-presenting cells, cytokine producers and precursors of autoantibody-secreting plasma cells. Therapeutic targeting of B cells aims to disrupt these self-reinforcing circuits rather than simply reduce autoantibody titres alone. Clinical experience with anti-CD20 monoclonal antibodies has validated B cells as therapeutic targets, while exposing key biological constraints, including incomplete tissue depletion, persistence of long-lived plasma cells, and BAFF-driven B cell repopulation. Recent advances including next-generation anti-CD20 monoclonal antibodies, bispecific T cell engagers and chimeric antigen receptor (CAR) T cell therapies have shown promise but questions remain relating to which patients should be treated with what modality of therapy and when this should be timed within the disease course. Herein, we evaluate the current landscape of B cell targeting therapies with particular focus on patient selection, timing of therapy and type of treatment.

Authors with CRIS profile

Georg Schett Lehrstuhl für Innere Medizin III Melanie Hagen Lehrstuhl für Innere Medizin III

Involved external institutions

King's College Hospital (KCH) GB United Kingdom (GB) University of Turin / Università degli Studi di Torino (UNITO) IT Italy (IT) Hôpitaux universitaires de Strasbourg (HUS) / University Hospital Strasbourg FR France (FR)

How to cite

APA:

Wincup, C., Gatto, M., Scherlinger, M., Schett, G., & Hagen, M. (2026). The why, what, who and when of B cell depletion in systemic lupus erythematosus: biological rationale, patient stratification and evolving therapeutic modalities. Rheumatology, 65(8). https://doi.org/10.1093/rheumatology/keag416

MLA:

Wincup, Chris, et al. "The why, what, who and when of B cell depletion in systemic lupus erythematosus: biological rationale, patient stratification and evolving therapeutic modalities." Rheumatology 65.8 (2026).

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