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尿液蛋白质组学中检测到的补体成分、蛋白水解相关蛋白和细胞通讯相关蛋白与IgA肾病有关。

Complement components, proteolysis‑related, and cell communication‑related proteins detected in urine proteomics are associated with IgA nephropathy.

作者信息

Mucha Krzysztof, Bakun Magdalena, Jaźwiec Radosław, Dadlez Michał, Florczak Michał, Bajor Małgorzata, Gala Kamila, Pączek Leszek

出版信息

Pol Arch Med Wewn. 2014;124(7-8):380-6. doi: 10.20452/pamw.2345. Epub 2014 Jun 18.

Abstract

INTRODUCTION

IgA nephropathy (IgAN) is the most common primary glomerulonephritis. The first symptoms of IgAN are erytrocyturia or hematuria, proteinuria, and decline in renal function, or any combination of the above. One of the promising diagnostic methods is urine proteomics.

OBJECTIVES

We studied urine proteomics in patients with IgAN and age- and sex‑matched healthy controls. To minimize the risk of protein degradation, we proposed a new protocol for urine collection and preparation.

PATIENTS AND METHODS

A total of 30 patients with IgAN and 30 controls were enrolled into the study. Thirty urine samples of the IgAN group were divided into 3 disease pooled samples (DPS I, II, and III) and 30 urine samples of the control group were divided into 3 control pooled samples (CPS I, II, and III). We used isoelectric focusing/liquid chromatography-mass spectrometry/mass spectrometry (IEF/LC‑MS/MS) to detect all proteins larger than 10 kDa.

RESULTS

Using qualitative analysis, we identified 761, 951, and 956 proteins in each of the 3 IEF/LC‑MS/MS experiments. The results were combined, yielding a dataset with 1238 proteins identified by at least 2 peptides. The statistical analysis of the quantitative results revealed 18 proteins that were differently populated in the urine of IgAN patients compared with healthy controls. We found increased urinary concentrations of complement components, coagulation factors, extracellular matrix, intracellular, transmembrane, and other proteins in patients with IgAN. Some of them have never been linked to IgAN before.

CONCLUSIONS

We demonstrated that urine proteomics is a promising tool for diagnosing and monitoring patients with IgAN.

摘要

引言

IgA肾病(IgAN)是最常见的原发性肾小球肾炎。IgAN的首发症状为红细胞尿或血尿、蛋白尿以及肾功能下降,或上述症状的任意组合。一种有前景的诊断方法是尿液蛋白质组学。

目的

我们研究了IgAN患者以及年龄和性别匹配的健康对照者的尿液蛋白质组学。为了将蛋白质降解风险降至最低,我们提出了一种新的尿液收集和制备方案。

患者与方法

共有30例IgAN患者和30名对照者纳入本研究。IgAN组的30份尿液样本被分为3个疾病混合样本(DPS I、II和III),对照组的30份尿液样本被分为3个对照混合样本(CPS I、II和III)。我们使用等电聚焦/液相色谱-质谱联用/质谱(IEF/LC-MS/MS)检测所有分子量大于10 kDa的蛋白质。

结果

通过定性分析,我们在3次IEF/LC-MS/MS实验中的每次实验中分别鉴定出761、951和956种蛋白质。将结果合并,得到一个由至少2种肽段鉴定出1238种蛋白质的数据集。定量结果的统计分析显示,与健康对照相比,IgAN患者尿液中有18种蛋白质的含量存在差异。我们发现IgAN患者尿液中补体成分、凝血因子、细胞外基质、细胞内、跨膜和其他蛋白质的浓度升高。其中一些蛋白质以前从未与IgAN相关联。

结论

我们证明尿液蛋白质组学是诊断和监测IgAN患者的一种有前景的工具。

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