Ivanova L V, Shilov E M, Ivanov A A, Kozlovskaia L V, Rudolph P, Proppe D
Ter Arkh. 2003;75(6):11-7.
To study expression of topoisomerases (TI) I and II alpha (DNA-bound enzymes involved in transcription and replication) in renal tissue as markers of activity and prognosis of glomerulonephritis (GN) decisive for choice of immunodepressive therapy.
TI expression was studied immunohistochemically in renal biopsies from 177 patients with different morphological variants of GN and in the samples of unaffected kidney tissue removed in 12 patients for local tumors.
There are definite differences between proliferative and non-proliferative GN variants--elevation of TI levels and monocytic infiltration in proliferative GN. Focal-segmental glomerulosclerosis is characterized by a high TI II alpha level in mesangial cells and monocytic infiltration of the glomeruli which are typical for inflammation. A statistical relationship between TI levels in mesangial cells and glomerular epithelium suggests a pathogenetic relation between these links of the pathological process. Molecular markers of activation and proliferation of cells and direct inductors of the inflammatory process (cells of monocytic infiltrate) closely correlated with the activity index--an integral indicator of inflammatory activity, as well as with the integral indicator of sclerotic processes in renal tissue--sclerosis index. Monocytic infiltration in the interstitium correlated both with morphological manifestations of activity, progression of nephritis and their clinical equivalents. In high TI expression GN resistance to immunodepressive therapy rose. To overcome the resistance, immunodepressive therapy must be more active--large doses and duration of treatment. In patients with lupus nephritis and mesangiocapillary GN renal prognosis was worse in the presence of high TI expression in mesangial cells and epithelium of the renal canaliculi.
The authors are the first to demonstrate TI expression in renal tissue of GN patients, correlation of its level with activity of renal process as well as its role in prediction of response to treatment and the rate of renal failure progression. It is suggested that high TI expression entails a progressive course of GN.
研究拓扑异构酶（TI）I和IIα（参与转录和复制的DNA结合酶）在肾组织中的表达，作为肾小球肾炎（GN）活动和预后的标志物，这对于免疫抑制治疗的选择具有决定性意义。
采用免疫组织化学方法研究了177例不同形态学类型GN患者的肾活检组织以及12例因局部肿瘤切除的未受影响肾组织样本中的TI表达。
增殖性和非增殖性GN变体之间存在明显差异——增殖性GN中TI水平升高和单核细胞浸润。局灶节段性肾小球硬化的特征是系膜细胞中TI IIα水平高以及肾小球单核细胞浸润，这是炎症的典型表现。系膜细胞和肾小球上皮细胞中TI水平之间的统计关系表明病理过程的这些环节之间存在发病机制联系。细胞活化和增殖的分子标志物以及炎症过程的直接诱导物（单核细胞浸润细胞）与活动指数——炎症活动的综合指标以及肾组织硬化过程的综合指标——硬化指数密切相关。间质中的单核细胞浸润与活动的形态学表现、肾炎进展及其临床等效指标均相关。在TI高表达的GN中，对免疫抑制治疗的耐药性增加。为克服耐药性，免疫抑制治疗必须更积极——大剂量和长疗程。在狼疮性肾炎和系膜毛细血管性GN患者中，系膜细胞和肾小管上皮细胞TI高表达时肾脏预后较差。
作者首次证明了GN患者肾组织中TI的表达，其水平与肾脏疾病活动的相关性以及其在预测治疗反应和肾衰竭进展速度中的作用。提示TI高表达导致GN病程进展。
