Anti-CD20 Rituximab Prevents Interleukin-13-Induced Cytoskeletal Remodeling of Human Podocytes Via Off-Target Effects

This is the authors' abstract. We don't add key points for this paper.

Nephrotic syndrome is characterized by massive proteinuria and hypoproteinaemia. The most common cause ofhigh proteinuria in childhood is idiopathic nephrotic syndrome (INS). Although steroid administration is very effective for INS, long-term treatment may cause a variety of side effects. Recently, rituximab (RTX), an anti-CD20antibody, was reported to be effective in refractory nephrotic syndrome. However, its therapeutic mechanism isuncertain because podocytes do not express CD20. Thus, we employed a podocyte cell line to examine the possibility that sphingomyelin phosphodiesterase acid-like 3b (SMPDL3B), an off-target of RTX, is responsible for thetherapeutic effects of rituximab in nephrotic syndrome. Using immortalized human podocytes, we first revealedthat RTX protects podocytes from IL-13-induced podocytopathy at the morphological level. Furthermore, themRNA expression of SMPDL3B in podocytes was significantly decreased by IL-13 treatment but reversed byRTX pretreatment. These results suggest that SMPDL3B in podocytes is a novel therapeutic target of RTX forpediatric nephrotic syndrome.