Masutani K, Tokumoto M, Nakashima H, Tsuruya K, Kashiwagi M, Kudoh Y, Fukuda K, Kanai H, Akahoshi M, Otsuka T, Hirakata H, Iida M
Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi, Fukuoka, Japan.
Clin Nephrol. 2003 Jun;59(6):395-405. doi: 10.5414/cnp59395.
Human immune response can be classified into 2 different subsets of T helper cells (Th1 and Th2) based on the pattern of cytokine production. In modern immunology, Th1/Th2 paradigm helps to explain the different inflammatory effector pathways and outcomes in human diseases. The present study was designed to determine the type of immunological response that influences anti-neutrophil cytoplasmic antibody-(ANCA) associated glomerulonephritis (GN) using cytokine analysis of peripheral T cells and diseased kidney tissues.
We analyzed peripheral blood Th1/Th2 ratio in 91 patients with primary GN, including 10 cases of ANCA-associated GN. Tissues were immunostained with markers of T cells and macrophages and osteopontin (OPN). Intrarenal expression of IFN-gamma and IL-4 mRNAs was evaluated by reverse transcriptase (RT)-PCR.
Peripheral Th1/Th2 ratio was significantly higher in ANCA-associated GN (19.4 +/- 9.4, mean +/- SD, n = 10), than those in healthy controls (7.6 +/- 4.1, n = 27), IgA nephropathy (9.6 +/- 5.6, n = 45), membranous nephropathy (7.1 +/- 4.4, n = 13), minimal-change nephrotic syndrome (8.2 +/- 4.5, n = 13) and focal segmental glomerulosclerosis (8.3 +/- 3.9, n = 10) (p < 0.01, each). In 7 of 10 cases of ANCA-associated GN, Th1/Th2 ratio decreased significantly after treatment with corticosteroid from 21.0 +/- 12.0 to 9.0 +/- 6.6 (p < 0.05). Immunohistochemical staining showed numerous infiltrating T cells, macrophages and OPN-positive cells in both glomerular tuft and cellular crescent; OPN-positive cell distribution was similar to that of macrophages. Intrarenal expression of IFN-gamma mRNA was strongly enhanced whereas a weak expression of IL-4 mRNA was observed especially in advanced cases showing tubulointerstitial injury.
Both peripheral and renal immune responses are strongly polarized toward Th1 type immune response in ANCA-associated GN. Peripheral Th1/Th2 ratio may reflect the immune responses in renal injury of ANCA-associated GN.
基于细胞因子产生模式，人类免疫反应可分为两种不同的辅助性T细胞亚群（Th1和Th2）。在现代免疫学中，Th1/Th2范式有助于解释人类疾病中不同的炎症效应途径和结果。本研究旨在通过对外周血T细胞和患病肾组织进行细胞因子分析，确定影响抗中性粒细胞胞浆抗体（ANCA）相关肾小球肾炎（GN）的免疫反应类型。
我们分析了91例原发性肾小球肾炎患者外周血Th1/Th2比值，其中包括10例ANCA相关肾小球肾炎患者。组织用T细胞、巨噬细胞和骨桥蛋白（OPN）标记物进行免疫染色。通过逆转录酶（RT）-PCR评估肾内干扰素-γ（IFN-γ）和白细胞介素-4（IL-4）mRNA的表达。
ANCA相关肾小球肾炎患者外周血Th1/Th2比值（19.4±9.4，均值±标准差，n = 10）显著高于健康对照组（7.6±4.1，n = 27）、IgA肾病（9.6±5.6，n = 45）、膜性肾病（7.1±4.4，n = 13）、微小病变肾病综合征（8.2±4.5，n = 13）和局灶节段性肾小球硬化症（8.3±3.9，n = 10）（各p < 0.01）。在10例ANCA相关肾小球肾炎患者中的7例，用皮质类固醇治疗后，Th1/Th2比值从21.0±12.0显著降至9.0±6.6（p < 0.05）。免疫组织化学染色显示，在肾小球毛细血管丛和细胞性新月体中均有大量浸润的T细胞、巨噬细胞和OPN阳性细胞；OPN阳性细胞分布与巨噬细胞相似。肾内IFN-γ mRNA表达强烈增强，而IL-4 mRNA表达较弱，尤其是在出现肾小管间质损伤的晚期病例中。
在ANCA相关肾小球肾炎中，外周和肾脏免疫反应均强烈偏向Th1型免疫反应。外周血Th1/Th2比值可能反映ANCA相关肾小球肾炎肾损伤中的免疫反应。
