Figure 1.

Potential immune mechanism of action of rituximab in childhood idiopathic nephrotic syndrome. Rituximab treatment can restore the immune homeostasis of pediatric patients with idiopathic nephrotic syndrome by directly (solid lines) or indirectly (dashed lines) affecting different B- and T-cell subsets. Rituximab directly depletes CD20-expressing transitional, mature, and memory B-cell subsets. In some days, also short-lived plasmablasts/plasma cells, which do not express CD20 antigen, are indirectly depleted due to their limited lifespan. B-cell depletion could affect the production of the described nephrotic syndrome–associated podocyte-damaging autoantibodies such as anti-CD40, anti-UCHL1, and antinephrin IgG^10–12 or cytokines such as IL-4, produced by B cells activated locally in the glomerulus.¹³ In addition, B-cell depletion can indirectly modulate the cross talk between B cells and specific T-cell subsets by affecting antigen presentation (MHC class II—TCR complex) and costimulation, resulting in a reduction of effector T cells such as Th2, Th17, T follicular helper (Tfh) cells, and invariant natural killer T (iNKT) cells and in a rise of regulatory T (Treg) cells.^14–17 Created with BioRender.com.