Masutani Kohsuke, Taniguchi Masatomo, Nakashima Hitoshi, Yotsueda Hideki, Kudoh Yuji, Tsuruya Kazuhiko, Tokumoto Masanori, Fukuda Kyoichi, Kanai Hidetoshi, Hirakata Hideki, Iida Mitsuo
Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Nephrol Dial Transplant. 2004 Mar;19(3):580-6. doi: 10.1093/ndt/gfg572.
Helper T (Th) cells are classified into Th1 and Th2 subsets based on cytokine production and the Th1/Th2 paradigm explains differences in inflammatory effector pathways in various human diseases. Membranous nephropathy (MN) is an immune complex disease associated with Th2 nephritogenic immune response. However, overproduction of interleukin (IL)-4, a principal Th2 cytokine, has not been demonstrated. We investigated Th1/Th2 cytokine production by peripheral Th cells and its association with the degree of proteinuria in MN.
We analysed production of Th1/Th2 cytokines, interferon (IFN)-gamma and IL-4 by peripheral Th cells, using an intracellular cytokine detection method with flow cytometry in patients with MN (n = 24). The data were compared with data from healthy subjects (n = 51), subjects with minimal change nephrotic syndrome (MCNS; n = 13) and subjects with focal segmental glomerulosclerosis (FSGS; n = 12). We compared the percentages of IFN-gamma+ and IL-4+ Th cells and the peripheral Th1/Th2 ratio (IFN-gamma/IL-4 ratio) among the four groups. We also examined the association of IFN-gamma and IL-4 production with clinical parameters of MN.
The mean percentage of IL-4+ cells in MN (3.9+/-1.2%) was significantly higher than in the control (2.4+/-1.0%), MCNS (2.3+/-1.4%) and FSGS (2.3+/-1.2%) groups (P<0.001, respectively). The Th1/Th2 ratio was significantly lower in MN (5.3+/-2.0) than in the control (8.2+/-4.2, P<0.05), MCNS (10.0+/-5.3, P<0.01) and FSGS (10.2+/-5.3, P<0.01) groups. Moreover, the percentage of IL-4+ cells correlated significantly with the amount of proteinuria in MN (r = 0.57, P<0.01).
IL-4 production by peripheral Th cells is up-regulated in patients with MN and correlated with the severity of proteinuria. Intracellular cytokine analysis could be a useful index in idiopathic MN.
辅助性T（Th）细胞根据细胞因子的产生被分为Th1和Th2亚群，Th1/Th2范式解释了各种人类疾病中炎症效应途径的差异。膜性肾病（MN）是一种与Th2致肾炎性免疫反应相关的免疫复合物疾病。然而，尚未证实主要的Th2细胞因子白细胞介素（IL）-4的过度产生。我们研究了外周Th细胞产生的Th1/Th2细胞因子及其与MN中蛋白尿程度的关系。
我们采用流式细胞术细胞内细胞因子检测方法，分析了MN患者（n = 24）外周Th细胞产生的Th1/Th2细胞因子、干扰素（IFN）-γ和IL-4。将数据与健康受试者（n = 51）、微小病变肾病综合征（MCNS；n = 13）和局灶节段性肾小球硬化症（FSGS；n = 12）受试者的数据进行比较。我们比较了四组中IFN-γ+和IL-4+ Th细胞的百分比以及外周Th1/Th2比值（IFN-γ/IL-4比值）。我们还研究了IFN-γ和IL-4产生与MN临床参数的关系。
MN组中IL-4+细胞的平均百分比（3.9±1.2%）显著高于对照组（2.4±1.0%）、MCNS组（2.3±1.4%）和FSGS组（2.3±1.2%）（P均<0.001）。MN组的Th1/Th2比值（5.3±2.0）显著低于对照组（8.2±4.2，P<0.05）、MCNS组（10.0±5.3，P<0.01）和FSGS组（10.2±5.3，P<0.01）。此外，MN组中IL-4+细胞的百分比与蛋白尿的量显著相关（r = 0.57，P<0.01）。
MN患者外周Th细胞产生IL-4上调，且与蛋白尿的严重程度相关。细胞内细胞因子分析可能是特发性MN的一个有用指标。
