B- and plasma cell-targeting therapies for podocytopathies: state of the art and the New Gaslini protocol
- 1Department of Medicine, Translational Transplant Research Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
- 2Nephrology, Dialysis and Transplantation Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
Abstract
Podocytopathies, including minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), and idiopathic nephrotic syndrome (INS), are traditionally classified by histology and corticosteroid responsiveness, but this framework does not capture their biological heterogeneity or underlying mechanisms. Over the past decade, the paradigm of podocyte injury has shifted from a T cell-centric model to a broader immunological framework in which B cells, plasma cells, and humoral immunity play a central role. The identification of circulating autoantibodies, including anti-nephrin antibodies, together with evidence of extrafollicular B-cell activation, supports a model in which humoral immune factors drive podocyte injury. Anti-CD20 therapies have improved outcomes in steroid-dependent and frequently relapsing disease, but their efficacy remains limited in steroid-resistant forms and post-transplant recurrence. This likely reflects incomplete depletion of tissue-resident B cells and persistence of long-lived plasma cells, supporting the need for strategies targeting multiple levels of the humoral immune axis. Recent studies suggest that combined targeting of CD20⁺ B cells and CD38⁺ plasma cells with monoclonal antibodies such as obinutuzumab and daratumumab may achieve deeper and more sustained disease control, including in refractory and recurrent cases. However, variability in treatment approaches across centers underscores the need for standardization. In this review, we summarize evidence supporting the role of humoral immunity in podocytopathies and discuss the strengths and limitations of B cell-directed therapies. We then propose a mechanistically driven strategy, the New Gaslini protocol, integrating sequential CD20 and CD38 targeting to provide a unified framework for managing severe and relapsing disease.
Related
- 618 A novel preclinical mouse model to investigate IL-18-targeting therapies
- Acupuncture-related therapies as an adjunct to opioid agonist therapy during active dose reduction in adults with opioid use disorder: protocol for a scoping review
- Current Evidence on the Use of Calcitonin Gene-Related Peptide-Targeting Therapies in Children and Adolescents.
- Assessing the translational value of animal models in developing pain-targeting therapies for clinical osteoarthritis
- PO021 | PLATELETS MATTER: THROMBIN GENERATION IN PLATELET‐RICH PLASMA VERSUS PLATELET-POOR-PLASMA UNDER NON-REPLACEMENT THERAPIES IN HAEMOPHILIA
BibTeX
@article{cravedi2026plasma,
title = {{B- and plasma cell-targeting therapies for podocytopathies: state of the art and the New Gaslini protocol}},
author = {Paolo Cravedi and Agnese Spennacchio and Carolina Bigatti and Xhuliana Kajana and Gianluca Caridi and Andrea Angeletti},
journal = {Clinical kidney journal},
year = {2026},
month = aug,
doi = {10.1093/ckj/sfag283},
url = {https://europepmc.org/article/PMC/PMC13716675},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - B- and plasma cell-targeting therapies for podocytopathies: state of the art and the New Gaslini protocol
AU - Paolo Cravedi
AU - Agnese Spennacchio
AU - Carolina Bigatti
AU - Xhuliana Kajana
AU - Gianluca Caridi
AU - Andrea Angeletti
PY - 2026
DA - 2026/08/21
JO - Clinical kidney journal
DO - 10.1093/ckj/sfag283
UR - https://europepmc.org/article/PMC/PMC13716675
AB - Podocytopathies, including minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), and idiopathic nephrotic syndrome (INS), are traditionally classified by histology and corticosteroid responsiveness, but this framework does not capture their biological heterogeneity or underlying mechanisms. Over the past decade, the paradigm of podocyte injury has shifted from a T cell-centric model to a broader immunological framework in which B cells, plasma cells, and humoral immunity play a central role. The identification of circulating autoantibodies, including anti-nephrin antibodies, together with evidence of extrafollicular B-cell activation, supports a model in which humoral immune factors drive podocyte injury. Anti-CD20 therapies have improved outcomes in steroid-dependent and frequently relapsing disease, but their efficacy remains limited in steroid-resistant forms and post-transplant recurrence. This likely reflects incomplete depletion of tissue-resident B cells and persistence of long-lived plasma cells, supporting the need for strategies targeting multiple levels of the humoral immune axis. Recent studies suggest that combined targeting of CD20⁺ B cells and CD38⁺ plasma cells with monoclonal antibodies such as obinutuzumab and daratumumab may achieve deeper and more sustained disease control, including in refractory and recurrent cases. However, variability in treatment approaches across centers underscores the need for standardization. In this review, we summarize evidence supporting the role of humoral immunity in podocytopathies and discuss the strengths and limitations of B cell-directed therapies. We then propose a mechanistically driven strategy, the New Gaslini protocol, integrating sequential CD20 and CD38 targeting to provide a unified framework for managing severe and relapsing disease.
SN - 2048-8505
SN - 2048-8513
ER -