INSERM, UMR S 702, Paris, France.
Proteomics. 2013 Jan;13(1):142-52. doi: 10.1002/pmic.201200267. Epub 2012 Dec 18.
IgA nephropathy (IgAN), the most common primary glomerulonephritis, is characterized by deposition of IgA in the glomerular mesangium. The diagnosis of IgAN still requires a kidney biopsy that cannot easily be repeated in the same patient during follow-up. Therefore, identification of noninvasive urinary biomarkers would be very useful for monitoring patients with IgAN. We first used bidimensional electrophoresis (2DE) coupled to MALDI-TOF-TOF and Western blot to identify some urinary biomarkers associated with IgAN. Urine of IgAN patients showed an increase of albumin fragments, α-1-antitrypsin and α-1-β-glycoprotein, along with a decrease of a single spot that was identified as the laminin G-like 3 (LG3) fragment of endorepellin. The urinary proteomes of 43 IgAN patients were compared to those of 30 healthy individuals by ELISA. Quantification of LG3 confirmed a significant decrease in the urine of IgAN patients compared to healthy controls, except in ten patients in whom LG3 was increased. These ten patients had a more severe disease with lower glomerular filtration rate values. We found a significant inverse correlation between LG3 levels and glomerular filtration rate in the 43 patients with IgAN, which was not observed in 65 patients with other glomerular diseases including membranous nephropathy (23), lupus nephropathy (13), focal segmental glomerulosclerosis (15), diabetic nephropathy (14), and six patients with nonglomerular diseases. Therefore, we suggest that the LG3 fragment of endorepellin could be associated with IgAN severity and might be related to pathogenesis of IgAN.
IgA 肾病(IgAN)是最常见的原发性肾小球肾炎,其特征是 IgA 在肾小球系膜沉积。IgAN 的诊断仍然需要肾活检,在随访过程中同一患者的肾活检不易重复。因此,识别非侵入性尿生物标志物对于监测 IgAN 患者非常有用。我们首先使用二维电泳(2DE)结合 MALDI-TOF-TOF 和 Western blot 来鉴定一些与 IgAN 相关的尿生物标志物。IgAN 患者的尿液显示白蛋白片段、α-1-抗胰蛋白酶和 α-1-β-糖蛋白增加,同时一种斑点减少,该斑点被鉴定为内皮抑制素的层粘连蛋白 G 样 3(LG3)片段。通过 ELISA 将 43 例 IgAN 患者的尿蛋白组与 30 名健康个体进行比较。LG3 的定量证实,与健康对照组相比,IgAN 患者的尿液中 LG3 明显减少,但在 10 例 LG3 增加的患者中除外。这 10 例患者的疾病更严重,肾小球滤过率值更低。我们发现 43 例 IgAN 患者的 LG3 水平与肾小球滤过率呈显著负相关,而在包括膜性肾病(23 例)、狼疮性肾炎(13 例)、局灶节段性肾小球硬化症(15 例)、糖尿病肾病(14 例)和 6 例非肾小球疾病患者在内的 65 例其他肾小球疾病患者中未观察到这种相关性。因此,我们认为内皮抑制素的 LG3 片段可能与 IgAN 的严重程度有关,可能与 IgAN 的发病机制有关。