Analysis of O-glycan heterogeneity in IgA1 myeloma proteins by Fourier transform ion cyclotron resonance mass spectrometry:: implications for IgA nephropathy
Analysis of O-glycan heterogeneity in IgA1 myeloma proteins by Fourier transform ion cyclotron resonance mass spectrometry:: implications for IgA nephropathy
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DOI：
10.1007/s00216-007-1500-z
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发表时间：
2007-11-01
影响因子：
4.3
通讯作者：
Novak, Jan
中科院分区：
文献类型：
--
作者：
Renfrow, Matthew B.;Mackay, C. Logan;Novak, Jan
伊加肾病（IgAN）是原发性肾小球肾炎的最常见形式。在IgAN中，铰链区（HR）中具有不完全半乳糖基化O-连接聚糖的IgA 1分子存在于系膜免疫沉积物和循环免疫复合物中。目前尚不清楚IgA 1蛋白中的半乳糖缺乏是随机发生还是优先发生在特定位点。我们先前已经证明了多个O-糖基化位点上的一个单一的IgA 1骨髓瘤蛋白的激活离子-电子捕获解离（AI-ECD）傅立叶变换离子回旋共振（FT-ICR）串联质谱法使用的第一个直接本地化。在这里，我们报告了使用FT-ICR MS和液相色谱FT-ICR MS分析IgA 1 O-聚糖异质性，以获得来自三种不同IgA 1骨髓瘤蛋白的IgA 1 HR糖肽的无偏准确质量谱。此外，我们报告了第一个AI-ECD片段上的一个人的IgA 1 O-糖肽从IgA 1 HR制备，是可重复的每一个IgA 1骨髓瘤蛋白。这些结果表明，未来的分析IgA 1 HR从IgAN患者和正常健康对照应该是可行的。
IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis. In IgAN, IgA1 molecules with incompletely galactosylated O-linked glycans in the hinge region (HR) are present in mesangial immunodeposits and in circulating immune complexes. It is not known whether the galactose deficiency in IgA1 proteins occurs randomly or preferentially at specific sites. We have previously demonstrated the first direct localization of multiple O-glycosylation sites on a single IgA1 myeloma protein by use of activated ion-electron capture dissociation (AI-ECD) Fourier transform ion cyclotron resonance (FT-ICR) tandem mass spectrometry. Here, we report the analysis of IgA1 O-glycan heterogeneity by use of FT-ICR MS and liquid chromatography FT-ICR MS to obtain unbiased accurate mass profiles of IgA1 HR glycopeptides from three different IgA1 myeloma proteins. Additionally, we report the first AI-ECD fragmentation on an individual IgA1 O-glycopeptide from an IgA1 HR preparation that is reproducible for each IgA1 myeloma protein. These results suggest that future analysis of IgA1 HR from IgAN patients and normal healthy controls should be feasible.