Ni Fen Fen, Liu Guang Lei, Jia Shi Lei, Li Cheng Rong, Gao Xiao Jie
Department of Nephrology, Shenzhen Children's Hospital, Shenzhen, China.
Department of Pediatrics, The Fifth Affiliated (Zhuhai) Hospital of Zunyi Medical University, Zhuhai, China.
Indian J Nephrol. 2023 Mar-Apr;33(2):93-100. doi: 10.4103/ijn.ijn_521_21. Epub 2023 Feb 20.
Immune dysfunction contributes to the progression of idiopathic nephrotic syndrome (INS), but the details of the pathogenesis of progression remain unknown. This study of children with INS investigated the relationship of activation of the mechanistic target of rapamycin (mTOR) pathway (PI3K/AKT/mTOR/p70S6K) with the levels of T helper 2/regulatory T (Th2/Treg) cells.
Twenty children with active INS (before steroid treatment), 20 children with remitting INS (INS-R, after steroid treatment), and 20 healthy control children (Ctrl) were enrolled. The levels of Th2/Treg cells in their peripheral circulatory systems were measured using flow cytometry, and the concentration of interleukin (IL)-4 was determined using a cytometric bead array (CBA). The levels of , , , , and transcription factors associated with Th2/Treg cells were measured using real-time polymerase chain reaction.
The INS group had a greater proportion of circulating Th2 cells; level of IL-4 protein; and levels of , , , , and mRNAs than the Ctrl group (all < 0.05), but a lower proportion of circulating Tregs and expression of (both < 0.05). Patients in the INS-R group had normalization of these markers (all < 0.05). Patients in the INS group had negative correlation in the percentage of Treg cells with Th2 cells and with IL-4 level and a negative correlation in the levels of and mRNAs.
Patients with active INS had an imbalance of Th2/Treg cells, which might result from the aberrant signaling of the mTOR pathway (PI3K/AKT/mTOR/p70S6K).
免疫功能障碍促进特发性肾病综合征（INS）的进展，但其进展的发病机制细节仍不清楚。本研究对INS患儿进行调查，以研究雷帕霉素作用靶点（mTOR）通路（PI3K/AKT/mTOR/p70S6K）的激活与辅助性T细胞2/调节性T细胞（Th2/Treg）水平之间的关系。
纳入20例活动期INS患儿（激素治疗前）、20例缓解期INS患儿（INS-R，激素治疗后）和20例健康对照儿童（Ctrl）。采用流式细胞术检测其外周循环系统中Th2/Treg细胞水平，采用细胞计数珠阵列（CBA）测定白细胞介素（IL）-4浓度。采用实时聚合酶链反应检测与Th2/Treg细胞相关的 、 、 、 及 转录因子水平。
与Ctrl组相比，INS组循环Th2细胞比例更高；IL-4蛋白水平更高； 、 、 、 及 信使核糖核酸水平更高（均P<0.05），但循环Treg比例更低且 的表达更低（均P<0.05）。INS-R组患者这些指标均恢复正常（均P<0.05）。INS组患者中，Treg细胞百分比与Th2细胞及IL-4水平呈负相关， 及 信使核糖核酸水平呈负相关。
活动期INS患者存在Th2/Treg细胞失衡，这可能是由mTOR通路（PI3K/AKT/mTOR/p70S6K）信号异常所致。
