Department of Pediatrics, Hirosaki University Hospital, 51 Hon-cho, Hirosaki, 036-8563, Japan.
Department of Pathology, The Jikei University School of Medicine, Tokyo, Japan.
Clin Exp Nephrol. 2021 Jan;25(1):44-51. doi: 10.1007/s10157-020-01970-0. Epub 2020 Sep 18.
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.
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 non-proteinuric controls.
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.
The expression of SMPDL-3b on podocytes is specifically decreased in paediatric-onset INS and its urinary excretion level reflects such conditions.
鞘磷脂磷酸二酯酶酸样 3b（SMPDL-3b）是细胞骨架的调节剂，在足细胞上表达。最近的报告表明，它是利妥昔单抗在治疗难治性肾病综合征中的直接靶点。然而，SMPDL-3b 对小儿特发性肾病综合征（INS）的治疗意义尚不清楚。本研究旨在探讨 SMPDL-3b 在尿液、血清和活检标本中的表达水平及其在 INS 患者治疗中的意义。
通过斑点印迹法分析 31 例 INS 患者（缓解 20 例，复发 11 例）尿液中 SMPDL-3b 的水平。为了进行精确的定量分析，我们通过液相色谱-串联质谱（LC-MS/MS）法检测了 10 例 INS 患者缓解期和复发期尿液中 SMPDL-3b 的排泄情况。采用酶联免疫吸附试验法检测 20 例 INS 患者（缓解 13 例，复发或初发 7 例）血清 SMPDL-3b 水平。此外，还比较了 INS 患者和蛋白尿性 IgA 肾病、狼疮性肾炎、非蛋白尿性对照患者活检标本中 SMPDL-3b 的免疫反应性。
通过斑点印迹法和 LC-MS/MS 法检测，INS 患者复发时尿液中 SMPDL-3b 的排泄量明显低于缓解期和其他类型蛋白尿性肾小球疾病或对照组。另一方面，INS 缓解期和复发期患者血清 SMPDL-3b 水平无差异。缓解期 INS 患者肾小球 SMPDL-3b 的免疫反应性与对照组几乎相同。
SMPDL-3b 在足细胞上的表达在小儿特发性肾病综合征中特异性降低，其尿液排泄水平反映了这种情况。
