Longitudinal Peripheral Immunophenotyping and Rituximab Response in Primary Membranous Nephropathy: A Prospective Cohort Study

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.