Longitudinal Peripheral Immunophenotyping and Rituximab Response in Primary Membranous Nephropathy: A Prospective Cohort Study
6 affiliations
- 1Department of Nephrology, University of Ioannina and University Hospital of Ioannina, Stavrou Niarchou Avenue, 45500 Ioannina, Greece
- 2Laboratory of Hematology—Unit of Molecular Biology, University Hospital of Ioannina, 45500 Ioannina, Greece
- 3First Pathology Laboratory, General Hospital of Athens “Laiko″, 11527 Athens, Greece
- 4Department of Radiology, University Hospital of Ioannina, 45500 Ioannina, Greece
- 5Department of Pediatrics, University Hospital of Ioannina, 45500 Ioannina, Greece
- 6First Department of Internal Medicine, University Hospital of Ioannina, 45500 Ioannina, Greece
Abstract
Rituximab (RTX) is a first-line option for primary membranous nephropathy (pMN), but many patients fail to respond for reasons that conventional markers only partially explain. We assessed whether longitudinal peripheral immunophenotyping could identify cellular biomarkers of response. In a prospective single-center cohort of 35 patients with pMN treated with standard two-dose RTX, flow cytometry of B-cell, T-cell and monocyte compartments, the systemic inflammation response index (SIRI) and phospholipase A2 receptor antibody were assessed at baseline and months 3, 6 and 12. Within a mean of 7.48 ± 2.4 months, 23 patients (65.7%) achieved either partial or complete remission. By month three, responders showed deeper B-cell depletion, higher CD4+CD25+FoxP3+ T cells, fewer intermediate monocytes and a lower SIRI. On multivariate analysis, month-3 depletion of total CD3−CD19+ B cells below 0.5% (odds ratio 5.8, 95% confidence interval 1.1–31.1) was associated with remission, and each 0.1-unit increase in month-3 SIRI (odds ratio 0.44, 95% confidence interval 0.22–0.91) with lower odds of remission. In a hypothesis-generating analysis, a model combining both had an apparent area under the curve of 0.87. Longitudinal immunophenotyping identifies candidate biomarkers of RTX response in pMN that require multicenter validation.
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BibTeX
@article{georgopoulos2026longitudinal,
title = {{Longitudinal Peripheral Immunophenotyping and Rituximab Response in Primary Membranous Nephropathy: A Prospective Cohort Study}},
author = {Christos Georgopoulos and Lefkothea Dova and Eleni Stamellou and Anila Duni and Georgios Vartholomatos and George Liapis and Vasileios Patsiogiannis and Ekaterini Siomou and Haralampos Milionis and Evangelia Dounousi},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = nov,
doi = {10.3390/ijms27219956},
url = {https://www.mdpi.com/1422-0067/27/21/9956},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Longitudinal Peripheral Immunophenotyping and Rituximab Response in Primary Membranous Nephropathy: A Prospective Cohort Study
AU - Christos Georgopoulos
AU - Lefkothea Dova
AU - Eleni Stamellou
AU - Anila Duni
AU - Georgios Vartholomatos
AU - George Liapis
AU - Vasileios Patsiogiannis
AU - Ekaterini Siomou
AU - Haralampos Milionis
AU - Evangelia Dounousi
PY - 2026
DA - 2026/11/06
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219956
UR - https://www.mdpi.com/1422-0067/27/21/9956
AB - Rituximab (RTX) is a first-line option for primary membranous nephropathy (pMN), but many patients fail to respond for reasons that conventional markers only partially explain. We assessed whether longitudinal peripheral immunophenotyping could identify cellular biomarkers of response. In a prospective single-center cohort of 35 patients with pMN treated with standard two-dose RTX, flow cytometry of B-cell, T-cell and monocyte compartments, the systemic inflammation response index (SIRI) and phospholipase A2 receptor antibody were assessed at baseline and months 3, 6 and 12. Within a mean of 7.48 ± 2.4 months, 23 patients (65.7%) achieved either partial or complete remission. By month three, responders showed deeper B-cell depletion, higher CD4+CD25+FoxP3+ T cells, fewer intermediate monocytes and a lower SIRI. On multivariate analysis, month-3 depletion of total CD3−CD19+ B cells below 0.5% (odds ratio 5.8, 95% confidence interval 1.1–31.1) was associated with remission, and each 0.1-unit increase in month-3 SIRI (odds ratio 0.44, 95% confidence interval 0.22–0.91) with lower odds of remission. In a hypothesis-generating analysis, a model combining both had an apparent area under the curve of 0.87. Longitudinal immunophenotyping identifies candidate biomarkers of RTX response in pMN that require multicenter validation.
SN - 1422-0067
ER -