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基于磁珠分离和 MALDI-TOF 质谱分析的人类系统性红斑狼疮血清肽组图谱。

Serum peptidome patterns of human systemic lupus erythematosus based on magnetic bead separation and MALDI-TOF mass spectrometry analysis.

机构信息

The Second Clinical Medical College, Jinan University, Shenzhen People's Hospital, Shenzhen, Guangdong Province, PR China.

出版信息

Scand J Rheumatol. 2010 May;39(3):240-6. doi: 10.3109/03009740903456292.

DOI:10.3109/03009740903456292
PMID:20166849
Abstract

OBJECTIVES

Currently few studies have been reported to utilize matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) in rheumatic disease, especially in systemic lupus erythematosus (SLE). Our aim was to find differentially expressed disease-related and condition-specific peptides in sera from patients with SLE, as well as to develop and validate the peptide classification model for the diagnosis of SLE.

METHODS

Based on the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) 2000, 50 SLE patients were divided into two subgroups: 25 were defined as stable SLE (SLEDAI < or = 8) and 25 as active SLE (SLEDAI > 8). Twenty-five patients with rheumatoid arthritis (RA) and 24 healthy donors were also included and underwent analysis. We performed magnetic beads-based weak cation exchange chromatography (MB-WCX) for sample processing and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) for peptide profiling. ClinProt software 2.1 was used for data analysis and a genetic algorithm was modelled for class prediction.

RESULTS

A series of significant short peptides was detected. Classification models were developed to classify samples across normal controls, active SLE patients, and stable SLE patients, and achieved high capability of prediction and cross-validation. Blinded verification of the classification model showed 91.7% sensitivity in active SLE, 83.3% sensitivity in stable SLE, and 86.7% specificity in normal controls.

CONCLUSION

We have completed a preliminary study to describe the serum peptide profile of SLE and improve the diagnosis of SLE from an integrated perspective of peptide mass patterns.

摘要

目的

目前鲜有研究利用基质辅助激光解吸电离飞行时间质谱(MALDI-TOF-MS)技术在风湿性疾病中,尤其是在系统性红斑狼疮(SLE)中进行研究。我们的目的是在 SLE 患者的血清中找到差异表达的疾病相关和特异性肽,并开发和验证用于 SLE 诊断的肽分类模型。

方法

根据系统性红斑狼疮疾病活动指数(SLEDAI)2000 标准,将 50 例 SLE 患者分为两组:25 例为稳定 SLE(SLEDAI<或=8),25 例为活动 SLE(SLEDAI>8)。同时纳入 25 例类风湿关节炎(RA)患者和 24 例健康对照者进行分析。我们采用基于磁珠的弱阳离子交换色谱(MB-WCX)进行样本处理和基质辅助激光解吸电离飞行时间质谱(MALDI-TOF-MS)进行肽谱分析。ClinProt 软件 2.1 用于数据分析,遗传算法用于模型预测。

结果

检测到一系列有意义的短肽。建立分类模型以区分正常对照组、活动 SLE 患者和稳定 SLE 患者的样本,实现了高预测和交叉验证能力。分类模型的盲法验证显示,在活动 SLE 患者中具有 91.7%的敏感性,在稳定 SLE 患者中具有 83.3%的敏感性,在正常对照组中具有 86.7%的特异性。

结论

我们已经完成了一项初步研究,描述了 SLE 的血清肽谱,并从肽质量图谱的综合角度提高了 SLE 的诊断能力。

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