Biomarkers of lupus nephritis determined by serial urine proteomics.
Biomarkers of lupus nephritis determined by serial urine proteomics.
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通过连续尿液蛋白质组学确定的狼疮性肾炎生物标志物。
DOI：
10.1038/ki.2008.316
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发表时间：
2008-09
影响因子：
19.6
通讯作者：
Rovin, Brad H.
中科院分区：
文献类型：
--
作者：
Zhang, Xiaolan;Jin, Ming;Wu, Haifeng;Nadasdy, Tibor;Nadasdy, Gyongyi;Harris, Nathan;Green-Church, Kari;Nagaraja, Haikady;Birmingham, Daniel J.;Yu, Chack-Yung;Hebert, Lee A.;Rovin, Brad H.
狼疮性肾炎是系统性红斑狼疮（SLE）常见且严重的并发症。治疗通常需要使用免疫抑制药物，且可能伴有严重的副作用。若能够预测复发、复发严重程度及恢复情况，便可以更有效地实施治疗并降低毒性。我们假设，对SLE肾炎发作前、发作期间及发作后的系列尿液样本进行低分子量尿蛋白质组的蛋白质组学分析，将能够发现SLE肾脏发作的潜在生物标志物。本研究旨在验证这一假设。
研究使用了19例世界卫生组织（WHO）III、IV和V级SLE肾炎患者共25个发作周期的尿液。尿液样本包括基线样本，以及发作前、发作期和发作后的样本。对尿液进行分级分离，去除大于30kDa的蛋白质，然后点样到弱阳离子交换（CM10）蛋白质芯片上，通过表面增强激光解吸/电离飞行时间质谱（SELDI - TOF MS）进行分析。
SELDI - TOF MS筛选显示，在2 - 20kDa范围内有176种蛋白质离子，其中27种在特定的发作间隔期存在差异表达。通过串联质谱对芯片上的肽段进行测序，以明确鉴定选定的差异表达蛋白质离子。鉴定出的蛋白质包括20和25个氨基酸的铁调素异构体、α1 - 抗胰蛋白酶片段以及白蛋白片段。铁调素20在发作前4个月升高，在肾脏发作时恢复至基线水平，而铁调素25在肾脏发作时降低，在发作后4个月恢复至基线水平。
通过对狼疮性肾炎患者尿液进行SELDI - TOF蛋白质谱分析，发现了几种肾脏发作的候选生物标志物。为了验证这些候选物是否为真正的生物标志物，需要在独立的SLE队列中进一步鉴定和验证。
Lupus nephritis is a frequent and serious complication of systemic lupus erythematosus (SLE). Treatment often requires the use of immunosuppression, and may be associated with severe side effects. The ability to predict relapse, relapse severity, and recovery could be used to more effectively implement therapy and reduce toxicity. We postulated that a proteomic analysis of the low-molecular weight urine proteome using serial urine samples obtained before, during, and after SLE nephritis flares would demonstrate potential biomarkers of SLE renal flare. This study was undertaken to test our hypothesis. Urine from 25 flare cycles of 19 WHO Class III, IV, and V SLE nephritis patients was used. Urine samples included a baseline, and pre-flare, flare, and post-flare specimens. The urines were fractionated to remove proteins larger than 30 kDa, and spotted onto weak cation exchanger (CM10) protein chips for analysis by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). SELDI-TOF MS screening showed 176 protein ions between 2-20 kDa of which 27 were found to be differentially-expressed between specific flare intervals. On-chip peptide sequencing by integrated tandem mass spectrometry was used to positively identify selected differentially-expressed protein ions. The identified proteins included the 20 and 25 amino acid isoforms of hepcidin, a fragment of α1-antitrypsin, and an albumin fragment. Hepcidin 20 increased 4 months pre-flare and returned to baseline at renal flare, whereas hepcidin 25 decreased at renal flare and returned to baseline 4 months post-flare. Using SELDI-TOF urine protein profiling in lupus nephritis, several candidate biomarkers of renal flare were found. To verify these candidates as true biomarkers, further identification and validation are needed in an independent SLE cohort.
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影响因子：
5.8
作者：
Malyszko, J;Malyszko, JS;Mysliwiec, M
通讯作者：
Mysliwiec, M
影响因子：
3.3
作者：
Drew, PD;Franzoso, G;Ozato, K
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影响因子：
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作者：
Houssiau, FA;Vasconcelos, C;Cervera, R
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Cervera, R
影响因子：
20.3
作者：
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通讯作者：
Swinkels, D
影响因子：
2.6
作者：
Aringer, M;Smolen, JS
通讯作者：
Smolen, JS