Development of antirituximab antibodies in children with nephrotic syndrome

Rituximab is actively used as a rescue therapy for nephrotic syndrome (NS). The development of antidrug antibodies, including antirituximab antibodies (ARA) and human antichimeric antibodies (HACA), is reported with rituximab treatment in various diseases. Here we report two pediatric patients with NS who developed ARA. Rituximab was given as a rescue therapy for two patients with steroid-dependent NS. Both patients had been treated orally with glucocorticosteroid, methylprednisolone, and calcineurin inhibitors but experienced frequent relapses. With rituximab treatment, the patients remained in remission for several months. After the B-cell count recovered, the patients received a second course of rituximab administration and experienced a hypersensitivity reaction during drug infusion. CD19 cell counts rose despite treatment with rituximab. ARA titers were monitored before and after rituximab treatment, and the development of ARA after the second course of rituximab administration was confirmed. We report the development of HACA in two patients with NS who did not achieve B-cell depletion after repeated administration of rituximab. This report suggests that additional studies are needed to determine the incidence of ARA in patients with NS, and its clinical significance.