CD+4T淋巴细胞在激素敏感型肾病综合征发病中的作用研究

目的　明确激素敏感型肾病综合征T淋巴细胞致病因子的亚群来源 ,探讨CD 4T淋巴细胞在本病发病中的作用。方法　采用间接免疫荧光染色法测定肾病综合征患儿外周血CD 4、CD 8T细胞百分率 ,以及CD 4/CD 8比值 ;磺柳酸比浊法测定经大鼠尾静脉注射抗体结合 补体介导溶解法分离的患儿CD 4和CD 8T淋巴细胞培养上清液后的大鼠尿蛋白含量 ,电镜观察其肾小球超微结构与基底膜上阴离子位点改变。结果　 (1)肾病综合征活动期患儿外周血CD 4T淋巴细胞百分率为(33 4± 2 4) % ,与正常儿童比较差异无显著性 (P >0 0 5 ) ;CD 8T淋巴细胞百分率为 (15 5±4 5 ) % ,比正常儿显著降低 (P <0 0 1) ;CD 4/CD 8比值为 (2 2± 0 3) % ,比正常儿显著升高(P <0 0 1)。(2 )注射患儿CD 4T淋巴细胞培养上清液后 ,大鼠尿蛋白排泌量在 0～ 8h时间段由注射前的 (3 9± 0 6 )mg/ 2 4h显著增加到 (13 1± 4 3)mg/ 2 4h(P <0 0 0 1)。注射患儿CD 8T淋巴细胞培养上清液后 ,大鼠尿蛋白排泌量无明显变化 (P >0 0 5 )。蛋白尿大鼠出现肾小球上皮细胞足突融合、基底膜上阴离子位点显著减少。结论　注射患儿CD 4T淋巴细胞培养上清液可使大鼠出现一过性蛋白尿 ;CD 4T淋巴细胞功能紊乱 ,分泌致病因子是激素敏感型肾病综合     

中国与印度的儿童激素敏感型肾病综合征诊治指南的比较

通过比较我国与印度的儿童激素敏感型肾病综合征(SSNS)诊治指南,发现中国与印度指南诊断肾病综合征(NS)的2个必要条件基本一致,SSNS定义和SSNS初治方案相同;但在NS分型、肾活检指征、转诊指征和免疫接种等方面不同。借鉴印度指南,对我国指南的修订提出7点建议:在大量蛋白尿定义中增加"或尿清蛋白排出量>40 mg.m-2.h-1";将低蛋白血症的定义修改为"血清清蛋白<25 g.L-1";删除按临床表现分类,代之以"对临床表现为肾炎型肾病者做肾活检";按糖皮质激素反应分型"将原发性NS分为SSNS和激素耐药型NS 2型";增加"NS肾活检指征";增加"转诊于儿童肾脏病专科医师的指征"和"原发性NS患儿免疫接种"原则。     

肾病综合征患儿血T3，T4水平及其对激素疗效影响的临床探讨

肾病综合征(NS)由于病因复杂,病理类型繁多,给予强的松治疗效果往往不够满意,目前仍是肾病领域一大难题。故探讨可能影响疗效的各种因素,并对其加以纠正,是十分必要的。甲状腺和肾脏关系     

激素敏感型肾病综合征儿外周血单个核细胞凋亡的临床研究

目的 观察肾病综合征(NS)在强的松治疗前后激素敏感者外周血单个核细胞(PBMC)的细胞凋亡变化,以探讨PBMC凋亡在激素治疗中的意义及与尿蛋白的关系。方法37例激素敏感型NS儿分别于强的松治疗前和治疗后第2、4、6、8周采血,进行细胞凋亡形态学观察,计算百分率。结果 治疗前后2、4、6周比较差异均有显著性(P均<0.01);治疗后外周血PBMC与尿蛋白变化呈正相关关系。结论 激素敏感型NS儿使用足量强的松治疗可诱导外周血PBMC细胞凋亡增加,也诱导其病情缓解,当尿蛋白转阴后诱导细胞凋亡随之减少。     

肾病综合征激素耐药型的诊治

肾病综合征激素耐药型的诊治杨霁云肾上腺皮质激素（简称激素）用于治疗小儿肾病综合征（简称肾病）逾４０年，已作为该征之首选药用于临床。虽多数患儿可由之诱导缓解，但勤复发、激素依赖及激素耐药仍为治疗棘手的问题，而常称之“难治性肾病”。一、概述根据我国儿科肾...     

激素敏感型肾病综合征患儿血、尿血管内皮细胞生长因子的变化

目的观察激素敏感型肾病综合征(SSNS)患儿活动期及缓解期血清和尿血管内皮细胞生长因子(VEGF)水平的变化,并探讨其临床意义。方法以SSNS患儿30例为研究对象,年龄、性别匹配的正常健康儿童作对照,用液相芯片分析技术检测患儿在活动期与缓解期及正常健康儿童30例血清和晨尿VEGF水平,分析VEGF在SSNS患儿活动期及缓解期的变化。结果SSNS患儿活动期血VEGF水平[(186.62±106.21)ng/L]明显高于缓解期[(118.75±73.08)ng/L],同时也高于正常对照组[(108.64±54.75)ng/L](P均<0.05);缓解期与正常对照组相比,血VEGF无明显差异(P>0.05);SSNS患儿活动期晨尿VEGF水平[(201.66±100.46)ng/L]明显高于缓解期[(116.35±55.99)ng/L],也高于正常对照组[(99.94±42.07)ng/L](P均<0.05);缓解期与正常对照组相比,尿VEGF无明显差异(P>0.05)。结论VEGF在SSNS发生发展过程中起一定病理生理作用。     

小儿激素敏感型肾病综合征中IL-18水平变化及意义

目的 探讨IL-18水平与小儿激素敏感型肾病综合征(SSNS)蛋白尿发生的相关性。方法 观察29例SSNS患儿在活动期和缓解期血、尿IL-18、TNF-α、IL-10的水平变化及与各临床指标的相关性。结果 SSNS患儿活动期血、尿IL-18、TNE-α水平显著高于缓解期及正常儿童;活动期血、尿IL-10水平与缓解期差异无显著性;SSNS患儿血清IL-18水平与TNF-α水平、24h尿蛋白定量呈明显正相关,尿IL-18水平与血浆白蛋白水平呈明显负相关,血清、尿IL-18水平与血清IL-10水平无明显相关性。结论 IL-18促进了Th1免疫应答,是SSNS产生蛋白尿的重要介导因子。     

儿童激素耐药型肾病综合征的诊疗现状

儿童激素耐药型肾病综合征(SRNS)是指以泼尼松足量治疗＞4周尿蛋白仍为阳性者.SRNS诊断包括临床诊断、病理诊断和病因诊断.SRNS病因分为T淋巴细胞功能紊乱和肾小球滤过屏障的原发性缺陷2类.因T淋巴细胞功能紊乱所致的儿童SRNS推荐钙调蛋白磷酸酶抑制剂作为初始治疗方案.因肾小球滤过屏障的原发性缺陷所致儿童SRNS绝大多数对激素和免疫抑制剂耐药,治疗该类SRNS的新药急待研发.     

激素耐药型肾病综合征与CD2AP基因

CD2AP基因位于染色体6p12.3,编码CD2相关蛋白(CD2AP)。CD2AP对于维持肾小球足细胞裂孔隔膜结构和功能的完整性具有重要作用。CD2AP基因突变所致激素耐药型肾病综合征(SRNS)呈常染色体隐性遗传或常染色体显性遗传。CD2AP基因纯合突变导致早发型SRNS。CD2AP基因杂合突变可以增加患肾小球疾病的...     

卡介苗多糖核酸预防激素敏感型肾病综合征复发的临床观察

目的 探讨卡介苗多糖核酸(BCG-PSN)在激素敏感型肾病综合征(SRNS)治疗中的抗复发作用。方法 48例肾病综合征(NS)患儿随机分为观察组和对照组各24例,均采用标准强的松长程疗法,观察组加用BCG-PSN肌肉注射,0.5～1mg/次,每周3次,共12周。观察两组疗效差异。结果 观察组和对照组治疗后首次尿蛋白转阴平均天数、疗程中和疗程结束1年内复发的平均次数分别为14.92±3.50d和21.50±9.10d,0.42±0.65次和1.92±1.47次,0.67±0.87次和3.25±2.64次,P均<0.005或<0.01;观察组与对照组的频复发例数、不频复发例数和无复发例数分别是1、7、16例和5、14、5例,P分别>0.05、<0.05和<0.05。结论BCG-PSN治疗SRNS的抗复发疗效显著。其机制认为与BCG-PSN能改善患儿的Th1/Th2失衡和减少感染作用有关。     

Final height in children with steroid-sensitive nephrotic syndrome

BACKGROUND: Growth retardation following steroid treatment in children is a major problem. Reduction of steroid dose has been tried using immunosuppressive agents such as cyclosporine A or mizoribine in children with frequently relapsing nephrotic syndrome. Few reports concerning final height in steroid-sensitive nephrotic syndrome (SSNS) are available. METHOD: Patients who developed SSNS before 15 years of age and reached their final height were retrospectively studied by standard deviation score (SDS) of height and target height calculated by their parental height. RESULTS: A total of 34 patients were evaluated for their final height. The mean age at onset of SSNS was 8.0 years and the mean age at last follow up was 21.6 years. In total, 22 patients had frequent relapses and were treated with cyclophosphamide, mizoribine or cyclosporin A. All patients had normal renal function at the last evaluation. The mean final height was 168 cm in males and 155 cm in females. The mean height SDS was 0.37 at the time of onset and was -0.43 when they reached their final height (P = 0.0001). The final height was a mean of 2.5 cm below target height and was significantly lower than their siblings (P = 0.007). Final height of two boys who continued to have frequent relapses during puberty and were not treated with cyclosporin A was 146 and 150 cm. CONCLUSION: Final height in children with SSNS was slightly affected by steroid treatment and two patients had severe growth retardation.     

Bone mineral density in children with steroid-sensitive nephrotic syndrome

Objective  

To observe the influence of prednisolone treatment on bone mineral density (BMD) in children with idiopathic nephrotic syndrome.     

Multiple drug-resistant gene 1 in children with steroid-sensitive nephrotic syndrome

Background: A full dose of corticosteroid is required to induce complete remission (CR) in steroid‐sensitive nephrotic syndrome (SSNS), unless it is possible to taper and discontinue along with the course after CR. But the mechanism of this change in steroid sensitivity remains unknown. P‐glycoprotein (PGP) can eliminate given corticosteroids from cytoplasm, which results in corticosteroid resistance. Therefore, drug delivery was analyzed using real‐time polymerase chain reaction (PCR) of multiple drug‐resistant gene 1 (MDR1; encoding PGP) mRNA expression. Methods: Fourteen patients with SSNS (male/female: 14/0; age: 1–23 years; mean 10.4 years) were enrolled in the study. MDR1 mRNA gene expression of peripheral blood nucleated cells (PBNC), before and after CR (19 sets of blood samples), was quantified using real‐time PCR. Results: The MDR1 mRNA levels before CR were variable in each patient, but there was an apparent decrease in the MDR1 gene expression of PBNC after CR (P < 0.003). Conclusion: PGP may play a role in the tapering of corticosteroids after CR in SSNS.     

重症化脓性脑膜炎儿童血CD4~+CD25~+调节性T细胞的变化

目的初步探讨CD4~+CD25~+调节性T细胞(Tregs)在儿童重症化脓性脑膜炎病程早期的变化及其可能的作用。方法回顾性研究2014年8月至2015年12月入住PICU的39例严重化脓性脑膜炎患儿的临床资料,并根据患儿入院后12h内血Tregs降低与否分为无Tregs降低组和Tregs降低组(Tregs计数410个/mm3为降低),分析早期Tregs改变与临床表现、实验室指标和转归的关系。结果 39例患儿中,13例(33%)Tregs比例明显下降(31%),18例(46%)Tregs绝对计数下降(410个/mm~3)。4例病死患儿均来自于Tregs降低组。与无Tregs降低组比较,Tregs降低组患儿外周血白细胞低于正常的比例更高,血清降钙素原升高更显著(P0.05)。结论儿童重症化脓性脑膜炎患儿早期Tregs可能受到抑制,这与患儿炎症反应更重、病死率更高有关。     

CD4+CD25+Foxp3+调节性T细胞与IL-33在儿童哮喘发病机制中的作用

目的 探讨CD4+CD25+Foxp3+调节性T细胞(Treg)与IL-33在儿童哮喘发病中的作用.方法 采用流式细胞仪检测45例哮喘患儿(哮喘组)、50例呼吸道合胞病毒感染喘息患儿(喘息组)及40例健康儿童(对照组)外周血CD4+CD25+Foxp3+Treg细胞百分比,采用ELISA法检测各组外周血血清IFN-γ、IL-4、IL-5及IL-33浓度,进行比较分析.结果 哮喘组患儿体内CD4+CD25+Foxp3+Treg 水平较喘息组及对照组均降低(P<0.05);哮喘组患儿体内IL-33水平较喘息组及对照组均升高(P<0.05),哮喘组患儿体内CD4+CD25+Foxp3+Treg与IL-33呈负相关(r=-0.156,P<0.01).结论 在哮喘患儿发病机制中,CD4+CD25+Foxp3+Treg与IL-33可能存在相互作用.     

哮喘患儿外周血中CD4~+LAP~+调节性T细胞比例及功能变化研究

目的测定哮喘患儿外周血中CD4+LAP+调节性T细胞(CD4+LAP+Treg细胞)比例和功能的改变,探讨CD4+LAP+Treg细胞在哮喘发病中的作用。方法选取2014年3月至2015年9月确诊为哮喘的患儿75例为研究对象,依据病情将哮喘患儿分为哮喘急性期组(n=40)和哮喘缓解期组(n=35);另选取行健康体检儿童30例为健康对照组。采用流式细胞仪检测各组儿童外周血CD4+LAP+Treg细胞百分比;采用3H-脱氧胸腺嘧啶苷法检测各组CD4+LAP+Treg细胞的免疫抑制情况。结果哮喘急性期组患儿体内CD4+LAP+Treg比例(2.0%±1.0%)较缓解期组(4.1%±2.4%)及健康对照组(4.6%±3.0%)均降低(P0.05);哮喘急性期组患儿体内CD4+LAP+Treg细胞免疫抑制率(21%±4%)较缓解期组(55%±9%)及健康对照组(62%±11%)均降低(P0.05)。结论哮喘患儿外周血中CD4+LAP+Treg数量降低和抑制功能减弱可能参与了哮喘的急性发病过程。     

Short versus long initial prednisone treatment in steroid-sensitive nephrotic syndrome in children

A total of 184 children aged, 13 months to 11 years, suffering from their first attack of steroid-responsive nephrotic syndrome were included in a randomized study. They were treated according to three treatment protocols. All children received l-2mg of prednisone/kg body weight/day (up to 80 mg daily) for 4 weeks, and thereafter 1 mg/kg body weight/48 h for the next 4 weeks. Treatment was discontinued at this point in 44 children (protocol A); in 68 (protocol B) the dose was reduced by 25% each week, tapering off to 0 at the end of the third month, while in 72 children (protocol C), after the first 2 months of initial treatment the dose was reduced by 25% each month and tapered off to 0 by the end of the sixth month. All patients completed a 2-year follow-up period after withdrawal of prednisone. Treatment results were expressed as: percentage of children relapse-free within the first 6 months and 2 years after withdrawal of treatment, and average number of relapses per patient per year. The best results were obtained in children who had been treated for 6 months: 65.3% of them remained relapse-free within the first 6 months and 50% over the entire 2-year follow-up period; the number of relapses per patient per year in this group was 0.49. The respective values for children treated 2 and 3 months were: 36.4% and 32.4% for the 6-month period; 27.3% and 20.6% for the 2-year period; the numbers of relapses per patient per year were 0.79 and 0.77, respectively. The frequency of corticosteroid side effects such as transient hypertension and cushingoid obesity during the initial treatment, and growth retardation or recurrent "respiratory tract" infections observed during the following 2-year follow-up period, did not increase after prolongation of the initial treatment. Initial treatment period, steroid-sensitive nephrotic syndrome
J Ksiek, Department of Nephrology, Child Health Centre, 04-736 Warsaw, Poland     

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目的 观察原发性肾病综合征(PNS)患儿泼尼松治疗前后CD4+CD25+调节性T细胞(CD4+CD25+Tr)的变化,阐明肾上腺糖皮质激素治疗儿童PNS的免疫机制.方法 选择2004-2007年在深圳市儿童医院住院治疗的初发PNS患)L42例,其中激素敏感型32例,激素耐药型10例.同期25例健康体检儿童作为对照组.流式细胞术检测泼尼松治疗前后外周血CD3+CD4+CD8-、CD3+CD4-CD8+、CD4+CD25+Tr的比例,荧光定量聚合酶链反应(Real-time PCR)检测泼尼松治疗前后外周血单个核细胞(PBMC)叉头型基因P3(Foxp3)、细胞毒性T淋巴细胞相关抗原4(CTL-4)和糖皮质激素诱导的肿瘤坏死因子受体(GITR)基因mRNA的表达.结果 与对照组比较,PNS患儿外周血CD3+CD4+CD8-T细胞、CD3+CD4-CD8+T细胞、CD4+CD25+Tr比例无明显改变(P>0.05).激素敏感型PNS患儿CD4+CD25+Tr比例在泼尼松治疗后明显增高,差异有统计学意义(P<0.01);激素耐药型PNS患儿CD4+CD25+Tr比例在泼尼松治疗前后无明显改变(P>0.05).激素敏感型PNS患儿在泼尼松治疗后PBMC细胞Foxp3、CTLA-4和GITR基因mRNA的表达明显增高;而激素耐药型PNS患儿泼尼松治疗前后Foxp3、CTLA-4基因表达无明显改变,仅GITR表达明显增高.结论 泼尼松等肾上腺糖皮质激素类药物可通过上调激素敏感型PNS患儿CD4+CD25+调节性T细胞的表达发挥免疫治疗作用.     

CD4+CXCR5+Tfh细胞比例及其调控因素变化对哮喘患儿的影响

目的 探讨哮喘患儿外周血滤泡样辅助性T细胞(CD4+CXCR5+Tfh细胞)比例及其转录调控因子BCL-6、BLIMP-1的表达变化.方法 依据病情将64例哮喘患儿分为哮喘急性期组(n=36)和哮喘缓解期组(n=28),另选取同期在我院行健康体检儿童25例为对照组.流式细胞术检测各组外周血CD4+CXCR5+Tfh细胞数量;实时荧光定量 PCR仪检测各组转录调控因子BCL-6、BLIMP-1 mRNA表达;双抗夹心ELISA法检测血浆总IgE、IL-2、IL-6 、IL-21浓度水平.结果 哮喘急性期组患儿CD4+CXCR5+Tfh细胞比例明显高于对照组及哮喘缓解期组(PPPPPP+CXCR5+Tfh细胞数量呈正相关(分别r=0.76、0.46,均Pr=-0.68, P结论 外周血CD4+CXCR5+Tfh细胞比例增高可能参与了儿童哮喘的急性发病过程,转录调控因子BCL-6 及BLIMP-1 mRNA的异常表达,以及局部微环境中总IgE和细胞因子IL-2、IL-6、IL-21的浓度改变可能与哮喘患儿CD4+CXCR5+Tfh细胞分化异常有关.