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儿童特发性肾病综合征低IgG血症机制:哺乳动物雷帕霉素靶蛋白过表达对滤泡辅助性T细胞数量的可能影响 被引量:3

Mechanism of hypo-IgG in children with idiopathic nephrotic syndrome:the possible influence of mammalian target of rapamycin over expression on follicular helper T cells
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摘要 目的探讨儿童特发性肾病综合征(INS)的低免疫球蛋白(Ig)G血症可能机制。方法选择2015年9月至2016年10月,于深圳市儿童医院接受治疗的40例激素敏感型INS患儿为研究对象。按照患儿病情,将其分为INS初发组(n=20)和INS缓解组(n=20),选择同期在该院接受健康体检的同年龄健康儿童纳入对照组(n=20)。采用流式细胞术(FCM)检测受试儿外周血单个核细胞(PBMC)中滤泡辅助性T细胞(Tfh,CD4+CXCR5+ICOShighT)、初始B细胞(CD19+CD27-IgD+B细胞)、转化前记忆B细胞(CD19+CD27+IgD+B细胞)、转化后记忆B细胞(CD19+CD27+IgD-B细胞)及浆细胞(CD19+CD27+IgD-CD38highB细胞)百分比;采用逆转录-聚合酶链反应(RT-PCR),检测受试儿外周血CD4+T细胞相关基因mRNA表达水平;采用酶联免疫吸附试验、免疫荧光吸附试验,分别检测受试儿血浆白细胞介素(IL)-2水平、丙二醛浓度。采用单因素方差分析及最小显著性差异(LSD)-t法,对上述指标分别进行3组间及组间两两比较;对其中部分指标的相关性,采用Pearson相关分析法。本研究通过深圳市儿童医院伦理委员会批准(批准日期:2016-04-11),所有受试对象监护人知情并同意。结果①INS初发组患儿血清总蛋白及白蛋白水平,以及血浆总IgG、IgG1、IgG2、IgG4水平等6项指标,均显著低于对照组健康儿童,血清总胆固醇浓度,则显著高于对照组,并且差异均有统计学意义(P<0.05)。②INS初发组患儿PBMC中Tfh百分比为(3.9±1.2)%,显著低于对照组的(5.2±1.1)%及INS缓解组的(4.9±1.2)%,并且差异均有统计学意义(P=0.001,P=0.021)。③INS初发组患儿PBMC中,转化后记忆B细胞、浆细胞百分比为(8.4±3.6)%、(7.5±2.0)%,均低于INS缓解组患儿的(11.6±2.7)%、(11.4±3.9)%及对照组健康儿童的(12.2±3.7)%、(12.5±3.4)%,并且差异均有统计学意义(均为P<0.001)。④INS初发组患儿的8项指标,如CD4+T细胞相关基因B淋巴细胞诱导成熟蛋白(Blimp)-1、IL-2Rα、IL-2Rβ� Objective To investigate the possible mechanism of hypogammaglobulinemia in pediatric idiopathic nephrotic syndrome(INS).Methods A total of 40 children with steroid-sensitive INS from September 2015 to October 2016 in Shenzhen Children′s Hospital were selected as research subjects.According to pathogenetic condition,they were divided into new onset INS group(n=20)and remission INS group(n=20).Meanwhile,in the same hospital there were 20 undergoing physical examination children with age matching the research subjects were enrolled into control group(n=20).The percentage of follicular helper T cell(Tfh,CD4+CXCR5+ICOShigh T cell),naive B cells(CD19+CD27-IgD+B cells),pre-transformed memory B cells(CD19+CD27+IgD+B cells),transformed memory B cells(CD19+CD27+IgD-B cells)and plasma cells(CD19+CD27+IgD-CD38high B cells)in peripheral blood mononuclear cell(PBMC)were analyzed by flow cytometry(FCM).Reverse transcription-polymerase chain reaction(RT-PCR)was performed to analyze mRNA expression level of CD4+T cells related genes in peripheral blood.Plasma level of interleukin(IL)-2 and plasma concentrations of malondialdehyde were detected by enzyme linked immunosorbent assay and immunofluorescence adsorption test,respectively.Clinical data were compared among three groups and pairwise compared between two groups using one-way ANOVA and least significant difference(LSD)-t test,respectively.And Pearson′s correlation analysis was used to analyze the correlation between some of two indexes.The study was approved by the Ethics Committee of Shenzhen Children′s Hospital(Approval date:April 11,2016),and all guardians of children signed the informed consent forms for clinical study.Results①The serum levels of total protein and albumin,also plasma immunoglobulin(Ig)G,IgG1,IgG2 and IgG4 of children with INS in new onset INS group were lower than those of control group,while serum total cholesterol concentration was higher than that of control group,and the differences were statistically significant(P<0.05).②The percentage of
作者 刘光磊 杨军 李成荣 Liu Guanglei;Yang Jun;Li Chengrong(Department of Nephrology and Immunology,Shenzhen Children′s Hospital,Shenzhen 518026,Guangdong Province,China;Department of Pediatrics,The Fifth Affiliated Hospital of Zunyi Medical University,Zhuhai,Zhuhai 519000,Guangdong Province,China)
出处 《中华妇幼临床医学杂志(电子版)》 CAS 2020年第2期171-180,共10页 Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition)
基金 国家卫生计生委公益性行业科研专项(201402012)。
关键词 肾病综合征 丙种球蛋白缺乏血症 免疫 体液 免疫球蛋白G T淋巴细胞 辅助诱导 雷帕霉素靶蛋白复合物1 雷帕霉素靶蛋白复合物2 儿童 Nephrotic syndrome Agammaglobulinemia Immunity,humoral Immunoglobulin G T-lymphocytes,helper-inducer Mechanistic target of rapamycin complex 1 Mechanistic target of rapamycin complex 2 Child
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