Precision immune reset in autoimmune kidney diseases: balancing the depth and cost of B-cell-targeted therapy
- 1Department of Nephrology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine
- 2National Clinical Research Center for Chinese Medicine
- 3Orthopedics and Traumatology, The Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine
Abstract
Treating autoimmune kidney diseases remains challenging because pathogenic B-cell activity spans circulating, tissue-resident, memory, and antibody-secreting compartments. Moreover, renal recovery often lags behind immunologic control. B-cell-targeted therapies now extend beyond anti-CD20 antibodies and include BAFF/APRIL blockade, CD19- and CD38-directed antibodies, bispecific T-cell engagers, and chimeric antigen receptor-engineered cells. This review examines the mechanistic and clinical evidence for these therapies in lupus nephritis, antineutrophil cytoplasmic antibody-associated glomerulonephritis, anti-glomerular basement membrane disease, membranous nephropathy, and IgA nephropathy. We interpret this evidence using a precision immune-reset framework that considers the dominant pathogenic compartment, the depth and durability of depletion, and the course of immune reconstitution. Anti-CD20 and BAFF/APRIL-directed therapies currently have the strongest disease-specific clinical support. Broader targeting of the B-cell lineage or plasma cells may help address tissue-persistent B cells and plasma-cell escape in selected patients with refractory disease. However, more extensive depletion may increase the risks of hypogammaglobulinemia, infection, impaired vaccine responses, cytopenias, delayed immune reconstitution, and treatment-specific toxicities. Suppression of pathogenic immunity also does not ensure rapid structural recovery of the kidney. We therefore propose a disease-specific framework that considers baseline immune reserve, pathogenic mechanisms, biomarker profiles, intrarenal activity, and the reversibility of kidney injury. Assessing both the suppression of pathogenic immunity and the recovery of protective immune function may improve the prospect of durable renal benefit while limiting unnecessary immunologic injury.
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BibTeX
@article{li2026precision,
title = {{Precision immune reset in autoimmune kidney diseases: balancing the depth and cost of B-cell-targeted therapy}},
author = {Yuchen Li and Xiaochen Li and Ziyu Guo and Yanni Li and Lerong Zhang and Jiamu Li and Chen Jiang},
journal = {Frontiers in Immunology},
year = {2026},
month = nov,
doi = {10.3389/fimmu.2026.1979283},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1979283/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Precision immune reset in autoimmune kidney diseases: balancing the depth and cost of B-cell-targeted therapy
AU - Yuchen Li
AU - Xiaochen Li
AU - Ziyu Guo
AU - Yanni Li
AU - Lerong Zhang
AU - Jiamu Li
AU - Chen Jiang
PY - 2026
DA - 2026/11/02
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1979283
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1979283/full
AB - Treating autoimmune kidney diseases remains challenging because pathogenic B-cell activity spans circulating, tissue-resident, memory, and antibody-secreting compartments. Moreover, renal recovery often lags behind immunologic control. B-cell-targeted therapies now extend beyond anti-CD20 antibodies and include BAFF/APRIL blockade, CD19- and CD38-directed antibodies, bispecific T-cell engagers, and chimeric antigen receptor-engineered cells. This review examines the mechanistic and clinical evidence for these therapies in lupus nephritis, antineutrophil cytoplasmic antibody-associated glomerulonephritis, anti-glomerular basement membrane disease, membranous nephropathy, and IgA nephropathy. We interpret this evidence using a precision immune-reset framework that considers the dominant pathogenic compartment, the depth and durability of depletion, and the course of immune reconstitution. Anti-CD20 and BAFF/APRIL-directed therapies currently have the strongest disease-specific clinical support. Broader targeting of the B-cell lineage or plasma cells may help address tissue-persistent B cells and plasma-cell escape in selected patients with refractory disease. However, more extensive depletion may increase the risks of hypogammaglobulinemia, infection, impaired vaccine responses, cytopenias, delayed immune reconstitution, and treatment-specific toxicities. Suppression of pathogenic immunity also does not ensure rapid structural recovery of the kidney. We therefore propose a disease-specific framework that considers baseline immune reserve, pathogenic mechanisms, biomarker profiles, intrarenal activity, and the reversibility of kidney injury. Assessing both the suppression of pathogenic immunity and the recovery of protective immune function may improve the prospect of durable renal benefit while limiting unnecessary immunologic injury.
SN - 1664-3224
ER -