Rituximab may affect T lymphocyte subsets balance in primary membranous nephropathy

Abstract

Background: The aim of this study was to investigate the effects and significance of rituximab (RTX) on the levels of T lymphocyte subsets in patients diagnosed with primary membranous nephropathy (PMN).

Methods: A total of 58 PMN patients and 25 healthy donors were chosen as the subjects. Among the PMN patients, 40 individuals received RTX treatment and completed at least 6 months of follow-up. All subjects underwent flow cytometry analysis to determine the peripheral blood lymphocyte subsets. The changes in anti-PLA2R antibody titers and 24-hour urinary protein levels were evaluated by ELISA and Biuret method before and after treatment.

Results: (1) The PMN group exhibited a significantly greater percentage of peripheral blood CD3^-CD19⁺ B cells than the healthy group, which is consistent with the findings of previous reports. Additionally, compared with those in the peripheral blood of healthy individuals, the numbers of CD4⁺ central memory T cells, CD4⁺ effector memory T cells, CD4⁺/CD8⁺, and CD4⁺CD25⁺ T cells in the PMN peripheral blood were markedly greater. However, the number of peripheral blood Treg cells was reduced in the PMN group. (2) After 6 months of RTX treatment, PMN patients exhibited significant decreases in anti-PLA2R antibody titers, 24-hour urinary protein levels, and peripheral blood CD3^-CD19⁺ B cells. Importantly, RTX administration decreased CD4⁺CD25⁺ T cells and CD4⁺/CD8⁺ in the peripheral blood of PMN patients and improved Treg cell levels. (3) RTX treatment induced alterations in the CD4⁺ T lymphocyte subsets in PMN patients, which did not correlate with B lymphocyte counts or anti-PLA2R antibody titers.

Conclusions: RTX treatment might have a beneficial impact on cellular immunity by effectively restoring the balance of CD4⁺ T lymphocyte subsets in PMN patients, which is beyond its effects on B cells and antibody production.

Trial registration: The research was registered at the First Affiliated Hospital of Soochow University.

Registration number: MR-32-23-016211. Registration Date: May 31, 2023.

Keywords: Anti-PLA2R antibody; B lymphocyte cells; Primary membranous nephropathy; Rituximab; T lymphocyte subsets.