淋巴细胞表型和细胞因子表达谱与IV型狼疮性肾炎患者免疫学发病机制  

Immunological mechanism of class IV lupus nephritis through lymphocyte subsets and cytokine proi le

作　　者：孙吉平[1] 赵菲[1] 张文静[1] 尹爱平[1] 

机构地区：[1]西安交通大学医学院第一附属医院肾病中心肾内科,西安710061

出　　处：《中南大学学报（医学版）》2014年第5期458-464,共7页Journal of Central South University ：Medical Science

基　　金：“十二五”国家科技支撑计划课题(2011BAI10B04);国家自然科学基金(81200528)~~

摘　　要：目的:通过研究外周血淋巴细胞亚群表达及细胞因子表达谱,探讨IV型狼疮性肾炎(LN)免疫发病机制。方法:30例经肾活检证实为IV型LN患者及30例肾活检证实为V型LN患者、30例年龄、性别匹配的健康对照均留取静脉血,分离血清,通过抗体芯片技术同时检测4种Th1细胞因子(INF-γ,IL-1,IL-2和TNF-α)和5种Th2细胞因子(IL-4,IL-5,IL-6,IL-10和IL-13)的表达;流式细胞仪检测外周血淋巴细胞亚型表达;Pearson相关性分析研究淋巴细胞亚型和细胞因子表达与临床指标之间的相关性。结果:IV型LN患者存在明显的贫血(P<0.001)、低补体血症及低白蛋白血症(P<0.05)。IV型LN患者CD3+细胞比率和计数与对照组之间无明显改变,但CD4+细胞比率和计数明显低于对照组(P<0.01);由于CD8+细胞与对照组无显著差异,从而出现CD4+/CD8+比值倒置(P<0.01);CD20+细胞比率及计数略高于对照组(P<0.05);但CD4+CD25+Foxp3+调节性T细胞比率及计数显著低于对照组(P<0.001);与V型LN患者相比,IV型LN患者淋巴细胞表型异常更显著,尤其表现在CD4+CD25+Foxp3+调节性T细胞(Treg)。与对照组相比,IV型LN患者体内存在广泛的细胞因子异常,检测的9种细胞因子中有7种明显升高,其中包括3种Th1细胞因子INF-γ(P<0.05),IL-2(P<0.05),TNF-α(P<0.01)和4种h 2细胞因子IL-4(P<0.05),IL-6(P<0.05),IL-10(P<0.01),IL-13(P<0.01);与IV型LN不同,V型LN仅有4种细胞因子表达上调,其中除IL-2属于Th1细胞因子外,其余3种为Th2细胞因子,包括IL-4,IL-10和IL-13。Pearson相关分析显示:调节性T细胞比率与多种临床指标之间存在负相关,包括24 h尿蛋白定量、antidsDNA滴度、疾病活动性指数等(r分别为-0.781,-0.746,-0.646;P<0.05);IL-5与anti-dsDNA滴度、血肌苷呈正相关(P<0.05),与补体C3呈负相关(P<0.05);IL-10与SLEDAI呈正相关(P<0.01),与尿蛋白、血红蛋白浓度均呈负相关(分别P<0.05和<0.001);IL-13与尿蛋白浓度呈负相关(r=-0.769,P<0.05);而V型LN患者Objective: To obtain a global view of lymphocyte subset changes in the peripheral blood and cytokine proi le in patients with class IV lupus nephritis(LN). Methods: A total of 30 patients with biopsy proven active class IV LN, 30 patients with biopsy proven active class V LN, and 30 healthy controls were enrolled. Serum concentration of Th1 cytokines(IFN-γ, IL-1, IL-2, and TNF-α) and Th2 cytokines(IL-4, IL-5, IL-6, IL-10, IL-13) were simultaneously analyzed by Fast Quant Human Th1/Th2 protein array. The expression of lymphocyte subsets was measured by flow cytometer. Clinical parameters such as urine protein of 24 h, autoantibodies and complement were detected. Pearson analysis was used to examine the relation between lymphocyte subsets and clinical parameters, cytokine and clinical parameters. Results: The patients with class IV LN had evident anemia(P<0.001), hypocomplementemia, and hypoalbuminemia(P<0.05). h ere were no signii cant dif erence both in the ratio and number of CD4+ lymphocytes between the controls and the patients. In the patients with class IV LN, the ratio and number of CD4+ lymphocytes were both lower than those of the controls(P<0.01). h e ratio and number of CD20+ lymphocytes were both higher than those of the controls(P<0.05), and a significant decrease in CD4+CD25+Foxp3+ regulatory T cells(Tregs) was observed in the patients compared with healthy age-matched controls(P<0.001). h e abnormality of lymphocytes in class IV patients was obviously notable, especially in CD4+CD25+Foxp3+ regulatory T cells. In class IV patients, most of the detected cytokines levels were markedly elevated as compared with the controls, including h 2 cytokines INF-γ(P<0.05), IL-2(P<0.05) and TNF-α(P<0.01), and h 2 cytokines IL-4(P<0.05), IL-6(P<0.05), IL-10(P<0.01) and IL-13(P<0.01). Only 4 out of 9 cytokines signii cantly increased in class V patients. In addition to IL-2, all of them belonged to h 2(IL-4, IL-10 and IL-13) cytokines. There was negative correlation between CD4+CD25+Foxp3+ regulatory cells and u

关 键 词：狼疮性肾炎 TH1细胞因子 TH2细胞因子 淋巴细胞 

分 类 号：R593.242[医药卫生—内科学]