Novel biomarkers for childhood idiopathic nephrotic syndrome

特发性肾病综合征是儿童最常见的肾脏疾病之一。然而，其病因尚不清楚。应用流式细胞仪检测11例特发性肾病综合征患儿T、B淋巴细胞表面共刺激分子CD2 6、CD2 8、CD80/CD86、CTLA-4、CD69、CD2 6的表达。结果表明，初发期患儿外周血中表达的CD40配体和CD19阳性B淋巴细胞上的CD40分子均显著高于缓解期和对照组。此外，Western印迹分析显示，位于CD40信号下游的磷酸化垃圾蛋白(p-Junk)仅在活动期肾病患者中表达。提示CD40和CD40配体介导的T、B淋巴细胞在肾病综合征的发病机制中可能起重要作用。此外，初发期血清可溶性CD30水平也显著高于缓解期和对照组。CD30也表达在活化的T淋巴细胞上。虽然还需要进一步的研究，但这一发现也表明T和B淋巴细胞之间存在相互激活。CD40、CD40配体和可溶性CD30可能是肾病综合征的良好候选生物标志物。

Idiopathic nephrotic syndrome is one of the commonest kidney diseases in children. However, its etiology is not elucidated yet. We have evaluated the expression of co-stimulatory molecules on T and B lymphocytes （CD26, CD28、CD80/CD86、CTLA-4、CD69、CD26）by flow cytometry in 11 children with idiopathic nephrotic syndrome. In the result, CD40 ligand expressed on CD4 positive T lymphocyte and CD40 molecule expressed on CD19 positive B lymphocyte are significantly increased at primary onset comparing to at remission and in control children. In addition, western blot analysis revealed that phosphorylated-junk (p-junk), which is in downstream of CD40 signal, is only expressed in patients in active nephorotic phase. These findings suggest that T and B lymphocytes through CD40 and CD40 ligand could play some important role in pathogenesis of nephrotic syndrome. In addition, serum level of soluble CD30 is also significantly increased at primary onset comparing to at remission and in control children. CD30 is also expressed on activated T lymphocyte. Although further investigation is necessary, this finding also suggests mutual activation between T and B lymphocytes. CD40, CD40 ligand and soluble CD30 may be a good candidate of biomarker of nephritic syndrome.