激素敏感型肾病综合征患儿记忆T淋巴细胞亚群精细分型的临床意义

Clinical significance of memory T lymphocyte subsets in children with steroid sensitive primary nephrotic syndrome

目的 探讨激素敏感型肾病综合征(steroid-sensitivenephroticsyndrome,SSNS)患儿初始糖皮质激素(glucocorticoid,GC)治疗前后记忆T淋巴细胞(memory T cell,T_(M))亚群精细分型的表达水平及临床意义。方法 选择35例初次发病SSNS患儿作为研究组,以20例健康体检儿童为正常对照组。采用多色流式细胞术分析比较研究组GC治疗前后及对照组TM亚群精细分型;酶联免疫吸附法(ELISA)检测各组T细胞因子水平,与临床指标做相关性分析。结果 研究组患儿GC治疗前CD4^(+)TM、CD4^(+)中央记忆T细胞(central memory T cell,T_(CM))、CD4^(+)效应记忆T细胞(effector memory T cell,TEM)、CD8^(+)TMcell、CD8^(+)TE_(M) cell百分比(占CD3^(+)T细胞)较缓解期和对照组升高,治疗前CD4^(+)初始T细胞(na?ve T cell,TN)较缓解期减少,差异均有统计学意义(P <0.05),治疗前记忆性干细胞样T细胞(stem-like memory T cells,T_(SCM))百分比较缓解期和对照组升高,差异有统计学意义(P <0.001);治疗前T细胞因子IL-1β、IL-8、IFN-γ较缓解期和对照组升高,差异有统计学意义(P <0.05);治疗前CD4^(+)TE_(M)cell比例与白蛋白水平、CD4^(+)T_(N)cell比例均呈明显负相关(P <0.01);与IFN-γ水平呈正相关(P <0.05)。结论 SSNS患儿存在T_(M)精细功能亚群和T_(SCM)分布异常,部分T细胞因子水平异常且与T_(M)亚群紊乱密切相关,共同参与疾病的发生发展;GC治疗干预了SSNS患儿T_(M)和T_(SCM)功能亚群的分布,为SSNS患儿细胞免疫精准治疗提供理论依据。

Objective To investigate the level and clinical significance of fine typing of memory T lymphocyte subsets before and after initial glucocorticoid(GC)treatment in children with steroid-sensitivenephroticsyndrome(SSNS).Methods Thirty-five children diagnosed with SSNS for the first time were selected as the research group,and twenty healthy children were enrolled as the normal control group.Multicolor flow cytometry was adopted to analyze the fine typing of memory T lymphocyte subsets in children with SSNS before initial treatment and in remission after treatment,and in the control group.Immunosorbent assay(ELISA)was used to detect the level of T-cell cytokines ineachgroup,and then the correlation analysis was performed with clinical indexes.Results CD4~+memory T cells(TM),CD4~+central memory T(T_(CM))cells and CD4~+effector memory T cells(T_(EM))in the active phase of GC in the SSNS children before initial treatment,CD8~+CD45RO~+TM,CD8~+T_(EM)percentages(% of CD3~+T cells)were higher than those in the remission period and control group after treatment,and the CD4~+na?ve T cells(TN)in the active phase were statistically significantly decreased in number compared with those in the remission period(P<0.05),the percentage of stem-like memory T cells(T_(SCM))in the active phase was significantly higher than that in the remission phase and the control group(P<0.001).Before treatment,the number of T cell cytokines including IL-1β,IL-8 and IFN-γ in the active stage was significantly larger than those in the remission stage and control group(P<0.05)and CD4~+T_(EM)ratio was significantly negatively correlated withalbuminand CD4~+TNratio(P<0.01)and positively correlated with IFN-γ levels(P<0.05).Conclusion Abnormal distribution of T_(SCM)/TMsubsets and disturbance of some T cell cytokines were found in SSNS children,and there was a closed relationship between them,suggesting abnormal T_(SCM)/TMsubsets play an important role in the occurrence and development of the disease;GC application affected the distribution of TMand T_(SCM)functional subsets in children with SSNS.