利妥昔单抗对激素依赖型肾病综合征患儿T淋巴细胞亚群和尿CD80水平的影响

Effects of rituximab on T lymphocyte subsets and urinary CD80 levels in children with steroid-dependent nephrotic syndrome

目的:观察利妥昔单抗(RTX)对激素依赖型肾病综合征(SDNS)患儿T淋巴细胞亚群和尿CD80水平的影响。方法:选取2016年3月至2019年10月在本院儿科肾脏病科首次接受RTX治疗的28例SDNS患儿作为研究对象(SDNS组),另外选择28例健康儿童作为对照组。SDNS患儿在糖皮质激素诱导缓解期进行1~2次RTX输注(375 mg·m^(-2),间隔1周)。在治疗前和RTX治疗后1个月、复发时(复发亚组)或随访12个月(缓解亚组)采集外周血和尿液,采用多色流式细胞术分析外周血T、B细胞亚群;ELISA法检测尿CD80水平。结果:与对照组相比,SDNS组治疗前外周血表现出更高的Th17、Th1、Th2和记忆B细胞绝对计数,同时调节性T细胞(Treg)绝对计数减少(P<0.05);另外Th17/Treg之值升高,Th1/Th2之值降低,且尿CD80水平也明显升高(P<0.05)。与基线值相比,RTX治疗后1个月和复发时或随访12个月时患儿Th17/Treg之值和尿CD80水平均降低(P<0.05)。且复发亚组患儿Th17、Treg、Th1、Th2绝对计数、Th17/Treg之值以及尿CD80水平较缓解亚组波动范围小(P<0.05)。结论:RTX诱导的记忆B细胞损耗对辅助性T细胞,主要Th17/Treg之值和Th1/Th2之值有显著影响,且这种免疫失衡可能与患儿SDNS复发有关。

Objective:To observe the effects of rituximab(RTX)on T lymphocyte subsets and urinary CD80 levels in children with hormone-dependent nephrotic syndrome(SDNS).Methods:A total of 28 SDNS children who received RTX treatment for the first time in the Department of Pediatric Nerology of our hospital from March 2016 to October 2019 were selected,and 28 healthy children were selected as controls.SDNS children received RTX infusion 1 to 2 times during the glucocorticoid-induced remission period(with each dose of 375 mg·m^(-2) for an interval of 1 week).Peripheral blood and urine samples were collected before treatment and 1 month after RTX treatment,at recurrence(recurrent subgroup,n=13 cases)or after 12 month of followed-up(remission subgroup,n=15 cases).T lymphocyte subsets were analyzed by multi-color flow cytometry and urinary CD80 levels were detected by ELISA.Results:Compared with the control group,the absolute counts of Th17,Th1,Th2 and memory B cells and the absolute counts of regulatory T cells(Treg)were higher in the peripheral blood of SDNS children before treatment(P<0.05).In addition,the ratio of Th17/Treg was increased,the ratio of Th1/Th2 was decreased,and the level of urinary CD80 was also significantly increased(P<0.05).Compared with baseline values,the Th17/Treg ratio and urinary CD80 levels were reduced at 1 month after RTX treatment and at relapse or 12 months of follow-up(P<0.05).The absolute count of Th17,Treg,Th1,Th2,the ratio of Th17/Treg and the level of CD80 in urine in the relapsed subgroup were smaller than those in the remission subgroup(P<0.05).Conclusion:Rituximab-induced memory B cell depletion significantly affects helper T cells,mainly the Th17/Treg ratio and Th1/Th2 ratio,and this immune imbalance may be related to the recurrence of hormone-dependent nephrotic syndrome in children.