Comprehensive analysis of short peptides in sera from patients with IgA nephropathy

Comprehensive analysis of short peptides in sera from patients with IgA nephropathy
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DOI:
10.1002/rcm.4315
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发表时间:
2009-12-01
影响因子:
2
通讯作者:
Kato, Tomohiro
Kato, Tomohiro
中科院分区:
化学3区
文献类型:
--
作者:
Kaneshiro, Nagayuki;Xiang, Yang;Kato, Tomohiro

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我们全面分析了血清短肽,以了解它们是否有助于伊加肾病(IgAN)的特征。检测了26例未经治疗的IgAN患者和25例健康供体的血清样品。通过基于磁珠的弱阳离子交换从血清样品中纯化的分子量类似于7 kDa的短肽,通过质谱检测。采用SIMCA-P+(R)主成分分析(PCA)和正交偏最小二乘判别分析(OPLS-DA)对检测到的肽峰进行多变量数据分析。在供试血清样品中共检测到92个肽峰。OPLS-DA分析显示,所有肽峰强度的曲线完全区分IgAN组和健康组,具有高R2值(0.919)和高Q2值(0.861)。此外,发现仅5个肽峰的图谱可区分这两组。通过串联质谱和数据库检索,在IgAN组中增加的5个肽中的3个被鉴定为纤维蛋白原α链的片段,并且在健康组中增加的2个肽被鉴定为补体C3 f和激肽原-1轻链的片段。总之,血清短肽的概况将有助于区分IgAN和健康状况。此外,这五种肽可能是IgAN的候选血清标志物,并可能与伊加的发病机制有关。版权所有(c)2009约翰威利父子有限公司。
We analyzed serum short peptides comprehensively to know whether they were useful to characterize IgA nephropathy (IgAN). Serum samples from 26 patients with untreated IgAN and 25 healthy donors were tested. Short peptides with molecular weights of similar to 7kDa, purified from the serum samples by magnetic-beads-based weak cation exchange, were detected by mass spectrometry. Then the peptide peaks detected were subjected to the multivariate data analysis by SIMCA-P+(R) containing principal component analysis (PCA) and orthogonal partial-least-squares-discriminate analysis (OPLS-DA). A total of 92 peptide peaks were detected in the tested serum samples. The OPLS-DA analysis revealed that the profile of all the peptide peak intensities discriminated the IgAN group and the healthy group completely with a high R2 value (0.919) and a high Q2 value (0.861). Further, the profile of only five peptide peaks was found to discriminate the two groups. By tandem mass spectrometry and database searching, three of the five peptides which increased in the IgAN group were identified as fragments of fibrinogen alpha chain, and the two peptides which increased in the healthy group were identified as fragments of complement C3f and kininogen-1 light chain. Taken together, the profile of the serum short peptides would be useful to discriminate IgAN and healthy conditions. Further, the five peptides may be candidate serum markers for IgAN and may be related to pathogenesis of IgA. Copyright (c) 2009 John Wiley & Sons, Ltd.