Association of Urinary Laminin G-Like 3 and Free K Light Chains with Disease Activity and Histological Injury in IgA Nephropathy
Association of Urinary Laminin G-Like 3 and Free K Light Chains with Disease Activity and Histological Injury in IgA Nephropathy
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DOI：
10.2215/cjn.05950612
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发表时间：
2013-07-01
影响因子：
9.8
通讯作者：
Gesualdo, Loreto
中科院分区：
文献类型：
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作者：
Rocchetti, Maria Teresa;Papale, Massimo;Gesualdo, Loreto
背景和目标 IgA 肾病具有不同的临床表现和进展。其明确诊断和预后需要肾活检。鉴定允许无创诊断和监测疾病活动的新生物标志物将是有利的。本研究分析了 IgA 肾病患者在疾病早期的尿液蛋白质组。设计、设置、参与者和测量通过表面增强激光解吸/电离飞行时间/质谱分析了 49 名 IgA 肾病患者、42 名 CKD 患者和 40 名健康个体的尿液。通过基质增强激光解吸/电离飞行时间/质谱法鉴定差异分泌的蛋白质，通过免疫学方法确认，并在一组独立的患者（14 名 IgA 肾病和 24 名 CKD）中进行验证。所有患者均于 2005 年 1 月至 2007 年 3 月在福贾大学肾病科入组。 结果 IgA 肾病中两种蛋白显着降低，分别为 21,598 和 23,458 m/z，分别为基底膜层粘连蛋白 G 样 3 肽和 Ig K 轻链。蛋白质印迹分析证实，与 CKD 患者和健康个体相比，IgA 肾病患者的层粘连蛋白 G 样 3 尿排泄量较低。免疫比浊法分析证实，与 CKD 患者和健康个体相比，IgA 肾病患者尿中游离 K 轻链的排泄量较低。免疫组织化学分析证实了 IgA 肾病中此类蛋白质的尿排泄情况。最后，尿液中游离 k 轻链和层粘连蛋白 G 样 3 浓度与 IgA 肾病队列的临床和组织学特征的严重程度呈负相关。结论 层粘连蛋白 G 样 3 和游离 K 轻链有助于 IgA 肾病疾病活动性的无创评估。
Background and objectives IgA nephropathy has variable clinical presentation and progression. Its definitive diagnosis and prognosis require renal biopsy. The identification of new biomarkers allowing noninvasive diagnosis and monitoring of disease activity would be advantageous. This study analyzed the urine proteome of IgA nephropathy patients at an early stage of disease.Design, setting, participants, & measurements Urine from 49 IgA nephropathy patients, 42 CKD patients, and 40 healthy individuals was analyzed by surface-enhanced laser desorption/ionization time of flight/mass spectrometry. Differentially excreted proteins were identified by matrix-enhanced laser desorption/ionization time of flight/mass spectrometry, confirmed by immunologic methods, and validated in an independent set of patients (14 IgA nephropathy and 24 CKD). All patients were recruited at the Division of Nephrology of the University of Foggia from January of 2005 to March of 2007.Results Two proteins, with 21,598 and 23,458 m/z, were significantly decreased in IgA nephropathy and identified as Perlecan laminin G-like 3 peptide and Ig K light chains, respectively. Western blot analysis confirmed the lower urinary excretion of laminin G-like 3 in IgA nephropathy patients compared with CKD patients and healthy individuals. Immunonephelometry analysis confirmed the lower urinary excretion of free K light chains in IgA nephropathy patients compared with CKD patients and healthy individuals. Immunohistochemistry analysis justified the urinary excretion profile of such proteins in IgA nephropathy. Finally, urinary free k light chains and laminin G-like 3 concentration inversely correlated with severity of clinical and histologic features of our IgA nephropathy cohort.Conclusions Laminin G-like 3 and free K light chains can contribute to the noninvasive assessment of IgA nephropathy disease activity.