Podocyte sphingomyelin phosphodiesterase acid-like 3b decreases among children with idiopathic nephrotic syndrome
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ORIGINAL ARTICLE
Podocyte sphingomyelin phosphodiesterase acid‑like 3b decreases among children with idiopathic nephrotic syndrome Shojiro Watanabe1 · Koji Hirono1 · Tomomi Aizawa1 · Koji Tsugawa1 · Kensuke Joh2 · Tadaatsu Imaizumi3 · Hiroshi Tanaka1,4 Received: 12 September 2019 / Accepted: 4 September 2020 © Japanese Society of Nephrology 2020
Abstract Aim Sphingomyelin phosphodiesterase acid-like 3b (SMPDL-3b), a regulator of the cytoskeleton, is expressed on podocytes. Recent reports present evidence that it is directly targeted by rituximab in the treatment of intractable nephrotic syndrome. However, the implications of SMPDL-3b for treatment of paediatric-onset idiopathic nephrotic syndrome (INS) remain unclear. This study aimed to investigate the level of expression of SMPDL-3b in urine, serum, and biopsy specimens and explore its implications in treatment of patients with INS. Methods Levels of urinary SMPDL-3b among 31 patients (20 in remission and 11 in relapse) with INS were analysed by dot blotting. For reference of precise quantitative analysis, we examined urinary excretion of SMPDL-3b from 10 patients with INS by liquid chromatography-tandem mass spectrometry (LC–MS/MS) in both remitted and relapsed status. The levels of serum SMPDL-3b among 20 patients (13 in remission and 7 in relapse or onset) with INS were also measured using enzyme-linked immunosorbent assay. Further, the immunoreactivity of SMPDL-3b in the biopsy specimens obtained from patients with INS was compared with those from patients with proteinuric IgA nephropathy, lupus nephritis, and nonproteinuric controls. Results Urinary excretion of SMPDL-3b in patients with INS was significantly decreased in relapse cases compared with cases of remission and other types of proteinuric glomerular disease or controls by both dot blotting and LC–MS/MS method. On the other hand, serum SMPDL-3b level in INS was not different between cases of remission and relapse. Glomerular immunoreactivity of SMPDL-3b in patient with INS in remission was almost the same level to that of control. Conclusion The expression of SMPDL-3b on podocytes is specifically decreased in paediatric-onset INS and its urinary excretion level reflects such conditions. Keywords Idiopathic nephrotic syndrome · Podocytes · Rituximab · Sphingomyelin phosphodiesterase acid-like 3B
Introduction
* Shojiro Watanabe [email protected] 1
Department of Pediatrics, Hirosaki University Hospital, 51 Hon‑cho, Hirosaki 036‑8563, Japan
2
Department of Pathology, The Jikei University School of Medicine, Tokyo, Japan
3
Department of Vascular Biology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
4
Department of School Health Science, Faculty of Education, Hirosaki University, Hirosaki, Japan
Rituximab, a specific monoclonal antibody to human CD20, has been successfully used to treat intractable nephrotic syndrome (frequent-relapse nephrotic syndrome and steroid-dependent nephrotic syndrome) among children [1–3]. Although depletion of B-cells is the pr
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