摘要
目的从系统生物学角度全面研究弥漫增生型狼疮肾炎（Ⅳ型LN）和膜型狼疮肾炎（V型LN）患者血清细胞因子表达谱。方法分离静脉血清，通过抗体芯片技术同时检测4种Th1和5种Th2细胞因子表达。结果①细胞因子表达谱：在检测的9种细胞因子中，Ⅳ型LN患者有7种明显升高，包括3种Th1细胞因子[干扰素（INF）-γ自细胞介素（IL）-2、肿瘤坏死因子（TNF）-α）]和4种Th2细胞因子（IL-4、IL-6、IL-10、IL-13）；而V型LN仅有4种细胞因子表达上调（IL-2、IL-4、IL-10和IL-13）。②相关性分析：IV型LN患者细胞因子与临床表现之间相关性较强，如IL-5与抗dsDNA抗体滴度及血肌酐呈正相关、与C3呈负相关；IL-10与系统性红斑狼疮（SLE）疾病活动指数（SLEDAI）呈正相关、与尿蛋白及血红蛋白浓度均呈负相关；IL—13与尿蛋白浓度呈负相关，IL-1与SLEDAI呈正相关、与血红蛋白浓度呈负相关。V型LN患者仅IL-1与血肌酐之间呈正相关，IL-4与尿蛋白之间呈负相关。结论不同病理分型的LN患者体内细胞因子表达谱不同，提示不同病理分型的LN其内在的免疫学发病机制存在差异，也提示不同的细胞因子表达可能代表不同类型的LN。
Objective To obtain a global view of cytokine profile in lupus nephritis （LN）, and to compare the pattern of cytokine profile in patients with different renal lesions, primarily diffuse proliferative lupus nephritis （IV-LN） and membranous lupus nephritis （V-LN）. Methods Thirtypatients with biopsy proven active LN （class IV, n=15; class V, n=15） and 15 healthy controls were enrolled in this study. Serum concentration of Thl 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 using Fast Quant Human Th1/Th2 protein array. Results （1） Cytokine profiling： in patients with class Ⅳ-LN, the levels of most of the detected cytokines elevated marked compared to normal controls, including both Thl （IL-2, INF-γ and TNF-α） and Th2 （IL-4, IL-6, IL-10 and IL-13 ） cytokines. Among them, both Th 1 （INF-γand TNF-α ） and Th2 （IL-6, IL- 10 and IL- 13 ） cytokines were 10 times higher than normal controls. However, patients with class V LN demonstrated a different cytokine profiling compared to class Ⅳ LN. Only 4 out of 9 cytokines were significantly increased. In addition to IL-2, all of those cytokines produced by Th2 （IL-4, IL-10 and IL-13） as well as IL-10 was 10 times higher than normal controls. The main difference of eytokines between patientswith class Ⅳ LN and patients with class V LN was among Thl cytokines （IFN-γ IL-2 and TNF-α）. There was a significant correlation between clinical manifestations and eytokines in class Ⅳ LN, especially among Th2 cytokine. There was positive correlation between IL-5 and anti-dsDNA titer（r=0.708, P〈0.05）, IL-5 and creatinin（r=0.681, P〈0.05 ） and IL-10 and SLEDAI scores （r=0.877, P〈0.01 ）. On the other hand, there was also negative correlation between some Th2 cytokines and clinical manifestations. There was negative correlation between IL-5 and complement C3 level （r=-01643, P〈0.05）, IL-10 and proteinuria（r=-0.659, P〈0.05）, IL-10 and hemoglobin level （r=-0.856, P〈 0.001 ）, as well as IL-13 and proteinuria （r=-0.769, P〈0;05）. In addition, IL-1 was positive correlated with SLEDAI, while it was negatively correlated with hemoglobulin level. As for class Ⅴ LN, there was positive correlation between IL-I and creatinin level （r=0.784, P〈0.05）, but negative correlation between IL-4 and proteinuria .（r=-0.754, P〈0.05 ）. Conclusion Patients with class Ⅳ renal lesion have shown a broad changes of cytokine activity, while up-regulation of Th2 cytokines is more predominant in patients with class Ⅴ LN. These suggest that the expression of different cytokines may be associated with different patterns of lupus renal lesions. These findings may shed light on the further exploring of the underlying mechanisms that mediate different patterns of renal lesions, as well as designing a rational therapeutic strategy for the treatment of LN.
出处
《中华风湿病学杂志》
CAS
CSCD
北大核心
2010年第1期8-12,共5页
Chinese Journal of Rheumatology
