Opportunities and limitations of B bell depletion approaches in SLE
Nature Review Rheumatol, 2025;21:111–126 DOI: 10.1038/s41584-024-01210-9
Stockfelt et al. reviewed the long-term efficacy and challenges of B cell depletion strategies in SLE. Rituximab, a CD20-targeting monoclonal antibody, has demonstrated efficacy in a subset of patients but remains limited by immunogenicity, residual B cells, and B-cell activating factor (BAFF)-mediated relapse. Newer strategies incorporating CAR T cells, bispecific T cell engagers, and combination therapies aim to enhance B cell depletion and optimise outcomes.
Based on rituximab’s off-label use in SLE, it is clear that deep and sustained B cell depletion correlates with improved clinical responses. However, resistance mechanisms, including tissue-resident B cells and innate immune activation, may necessitate alternative therapeutic targets beyond B cell depletion alone. Advances in genetic profiling may facilitate personalised treatment approaches to optimise immunological and clinical efficacy.
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