频繁复发肾病综合征患儿PD-L1+B细胞比例及意义研究

Proportion and role of PD-L1+B cells in children with frequent relapsing nephrotic syndrome

目的探讨频繁复发肾病综合征(FRNS)患儿外周血程序性死亡蛋白配体1阳性(PD-L1^(+))B细胞比例及意义,进一步探究FRNS的可能发病机制。方法选取2021年4月至2022年2月该院68例初次发病的原发性肾病综合征(PNS)患儿,随访1年,根据复发的频次,分为FRNS组(31例)和非频繁复发组(NFRNS,37例)。另选取同期该院门诊28例体检健康儿童作为健康对照组。于研究组患儿糖皮质激素(GC)治疗前、治疗缓解后及健康对照组儿童体检时分别采取静脉血标本。采用流式细胞术检测各组儿童外周血CD19^(+)PD-L1^(+)B细胞比例、CD19^(+)CD24^(hi)CD27^(+)B细胞、CD19^(+)CD24^(hi)CD38^(hi)B细胞。结果GC治疗前,与健康对照组比较,FRNS组、NFRNS组患儿外周血PD-L1^(+)B细胞比例均明显升高(P<0.05),CD19^(+)CD24 hi CD27^(+)B细胞比例均明显降低(P<0.05),CD19^(+)CD24^(hi)CD38^(hi)B细胞比例差异无统计学意义(P>0.05);与NFRNS组比较,FRNS组PD-L1^(+)B细胞比例明显升高(P<0.05),CD19^(+)CD24 hi CD27^(+)B细胞比例明显降低(P<0.05)。GC治疗后,FRNS组较NFRNS组及健康对照组的PD-L1^(+)B细胞比例均明显升高(P<0.05)。与治疗前比较,治疗后FRNS组、NFRNS组患儿外周血PD-L1^(+)B细胞比例均明显下降(P<0.05),CD19^(+)CD24 hi CD27^(+)B细胞比例均明显升高(P<0.05)。FRNS组GC治疗前PD-L1^(+)B细胞比例与总B细胞计数(r=0.528,P=0.002)、IgM(r=0.371,P=0.040)呈正相关,与ALB(r=-0.461,P=0.009)呈负相关。结论FRNS患儿中存在PD-L1^(+)B细胞、CD19^(+)CD24 hi CD27^(+)B细胞比例异常,其可能参与PNS患儿的频繁复发过程。

Objective To determine the proportion and significance of PD-L1^(+)B lymphocytes in the peripheral blood of children with frequent relapses nephrotic syndrome(FRNS)and to further investigate the possible pathogenesis of FRNS.Methods From April 2021 to February 2022,68 children with primary nephrotic syndrome(PNS)in this hospital were selected and followed up for 1 year,31 children were divided into FRNS group and 37 children into the non-frequent recurrence group(NFRNS).According to the frequency of recurrence,28 children from the outpatient health examination of this hospital during the same period were selected as healthy control.Blood samples were collected from children in each group before and after glucocorticoid(GC)treatment.The proportion of CD19^(+)PD-L1^(+)B lymphocytes,CD19^(+)CD24^(hi)CD27^(+)B lymphocytes,CD19^(+)CD24^(hi)CD38^(hi)B lymphocytes in the peripheral blood of children in each group was determined by flow cytometry.Results Before GC treatment,compared with the healthy control group,the proportion of PD-L1^(+)B cells in peripheral blood of children in FRNS group and NFRNS group increased significantly(P<0.05),and the proportion of CD19^(+)CD24^(hi)CD27^(+)B cells decreased significantly(P<0.05),while there was no significant difference in B cell proportion of CD19^(+)CD24^(hi)CD38^(hi)B cells(P>0.05).After GC treatment,the proportion of PD-L1^(+)B cells in FRNS group was significantly higher than that in NFRNS group and healthy control group(P<0.05).Compared with NFRNS group,the proportion of PD-L1^(+)B cells in FRNS group increased significantly(P<0.05),and the proportion of CD19^(+)CD24^(hi)CD27^(+)B cells decreased significantly(P<0.05).After GC treatment,the proportion of PD-L1^(+)B cells in FRNS group was significantly higher than those in NFRNS group and healthy control group(P<0.05).Compared with before treatment,the proportion of PD-L1^(+)B cells in peripheral blood of children after treatment in FRNS group and NFRNS group decreased significantly(P<0.05),and the proportion of CD19^(+)CD24^(hi)CD27^(+)B cells increased significantly(P<0.05).The proportion of PD-L1^(+)B lymphocytes in FRNS group before GC treatment was positively correlated with IgM(r=0.371,P=0.040),while negatively correlated with ALB(r=-0.461,P=0.009).Conclusion The proportion of PD-L1^(+)B cells and CD19^(+)CD24^(hi)CD27^(+)B cells in FRNS children is abnormal,which may be involved in the frequent recurrence process of PNS children.