Single-cell transcriptomic signatures of T cells associated with rituximab responsiveness in idiopathic nephrotic syndrome

Rituximab (RTX) is increasingly used in steroid-dependent minimal change disease, a leading cause of idiopathic nephrotic syndrome (INS), yet predictors of response remain unclear. Although RTX primarily targets B cells, T cells are also implicated in INS pathogenesis. We investigated RTX-induced T cell dynamics by single-cell RNA sequencing/T cell receptor profiling of peripheral T cells from three responders and three non-responders before and after RTX treatment. Responders exhibited RTX-driven broad transcriptomic remodeling, accompanied by reduced exhausted CD8 + T cells and clonal expansion of CD4 + cytotoxic T cells with enhanced oxidative phosphorylation (OXPHOS) signatures, whereas non-responders showed marginal changes. In a separate cohort, reactive oxygen species (ROS) levels tended to be higher in responders, and declined post-RTX, collectively associating enhanced mitochondrial activity with favorable response. Reanalysis of childhood INS data supported altered B–T cell crosstalk and T cell metabolism. Together, T cells may influence RTX responsiveness, warranting further biomarker studies.