Nephrology, Dialysis and Transplantation Unit, Regina Margherita Children's University Hospital, Piazza Polonia 94, 10127 Torino, Italy.
Clin J Am Soc Nephrol. 2011 Aug;6(8):1903-11. doi: 10.2215/CJN.11571210. Epub 2011 Jul 22.
We assessed the activation of the oxidative stress pathway in patients with IgA nephropathy (IgAN), while evaluating the classic marker of the disease (galactose-deficient serum IgA1).
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Sera from 292 patients and 69 healthy controls from Italy and the United States were assayed for advanced oxidation protein products (AOPPs), free sulfhydryl groups on albumin (SH-Alb), and IgA1 with galactose-deficient hinge-region O-glycans (Gd-IgA1). Gd-IgA1 was detected by binding to Helix aspersa agglutinin (HAA) and expressed as total Gd-IgA1 or as degree of galactose deficiency relative to a standard Gd-IgA1 myeloma protein (%HAA).
Sera from IgAN patients showed higher levels of Gd-IgA1, %HAA, and AOPPs, but lower levels of SH-Alb in comparison to that from healthy controls. Serum levels of AOPPs significantly correlated with serum Gd-IgA1 and %HAA. The relationship between these biomarkers and clinical features at sampling and during follow-up was assessed in 62 patients with long-term follow-up. AOPPs and %HAA correlated with proteinuria at sampling and independently associated with subsequent proteinuria. Levels of AOPPs correlated with rate of decline in renal function after sampling. The combination of a high level of AOPPs and a high level of %HAA associated with decline in estimated GFR.
Serum levels of aberrantly glycosylated IgA1 are elevated and oxidative stress pathways are activated in patients with IgAN; the intensity of the stress correlated with expression and progression of the disease. We speculate that oxidative stress may modulate the nephrotoxicity of aberrantly glycosylated IgA1 in IgAN.
我们评估了 IgA 肾病（IgAN）患者氧化应激途径的激活情况，同时评估了该疾病的经典标志物（半乳糖缺乏的血清 IgA1）。
设计、地点、参与者和测量：来自意大利和美国的 292 名患者和 69 名健康对照者的血清样本用于检测晚期氧化蛋白产物（AOPPs）、白蛋白上的游离巯基（SH-Alb）和具有半乳糖缺乏铰链区 O-聚糖的 IgA1（Gd-IgA1）。Gd-IgA1 通过与 Helix aspersa agglutinin（HAA）结合来检测，并表示为总 Gd-IgA1 或相对于标准 Gd-IgA1 骨髓瘤蛋白的半乳糖缺乏程度（%HAA）。
与健康对照组相比，IgAN 患者的血清 Gd-IgA1、%HAA 和 AOPPs 水平更高，而 SH-Alb 水平更低。血清 AOPPs 水平与血清 Gd-IgA1 和 %HAA 显著相关。在 62 例具有长期随访的患者中，评估了这些生物标志物与采样时和随访期间的临床特征之间的关系。AOPPs 和 %HAA 与采样时的蛋白尿相关，且独立与随后的蛋白尿相关。AOPPs 水平与采样后肾功能下降的速度相关。高水平的 AOPPs 和高水平的 %HAA 与估计肾小球滤过率的下降相关。
IgAN 患者血清中异常糖基化的 IgA1 水平升高，氧化应激途径被激活；应激的强度与疾病的表达和进展相关。我们推测氧化应激可能调节 IgAN 中异常糖基化 IgA1 的肾毒性。
