Targeting B Cells and Plasma Cells in Glomerular Disease.
This JASN review describes therapies that target B cells and plasma cells in glomerular disease. It covers anti-CD20 depletion, BAFF/APRIL and B-cell receptor inhibition, proteasome and anti-CD38 plasma-cell therapies, and newer CAR-T and bispecific T-cell engager approaches.
Background
Loss of tolerance and the production of self-reactive autoantibodies are central to the pathogenesis of many glomerular diseases. Plasmablasts and plasma cells, the end products of B-cell development in the bone marrow and secondary lymphoid tissues, produce these antibodies. B cells also present antigen to T cells and produce proinflammatory cytokines. Nontargeted immunosuppression is effective but has multiple side effects, and a high proportion of patients still have resistant disease.
Study design
This is a narrative review in the Journal of the American Society of Nephrology (Ahmad and Jefferson, University of Washington). It reviews the biology of antibody-secreting cells and focuses on therapeutics that specifically target B cells and plasma cells. It is not a primary trial and reports no pooled outcome data.
Key findings
The review covers B-cell depletion strategies: anti-CD20 monoclonal antibodies, inhibition of B-cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL), and B-cell receptor inhibition. It describes their role in different glomerular diseases and outlines reasons for therapeutic resistance. It also covers plasma cell-directed therapies, including proteasome inhibition and anti-CD38 antibodies, and discusses novel approaches such as chimeric antigen receptor (CAR) T-cell therapy and bispecific T-cell engagers.
Clinical implications
Clinicians managing antibody-mediated glomerular disease that resists conventional immunosuppression can use this overview of targeted B-lineage and plasma-cell options to see where each therapy fits and why some patients do not respond.
Category
Research
Source
J Am Soc Nephrol
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