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从人血清中对急性相炎症蛋白进行精确的 NMR 定量分析。

Towards a Precise NMR Quantification of Acute Phase Inflammation Proteins from Human Serum.

机构信息

Institute of Chemistry and Metabolomics, University of Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany.

Institute of Nutritional Medicine, University of Lübeck and Medical Center Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany.

出版信息

Angew Chem Int Ed Engl. 2023 Aug 28;62(35):e202306154. doi: 10.1002/anie.202306154. Epub 2023 Jul 17.

DOI:10.1002/anie.202306154
PMID:37341676
Abstract

Nuclear Magnetic Resonance (NMR) spectra of human serum and plasma show, besides metabolites and lipoproteins, two characteristic signals termed GlycA and B arising from the acetyl groups of glycoprotein glycans from acute phase proteins, which constitute good markers for inflammatory processes. Here, we report a comprehensive assignment of glycoprotein glycan NMR signals observed in human serum, showing that GlycA and GlycB signals originate from Neu5Ac and GlcNAc moieties from N-glycans, respectively. Diffusion-edited NMR experiments demonstrate that signal components can be associated with specific acute phase proteins. Conventionally determined concentrations of acute phase glycoproteins correlate well with distinct features in NMR spectra (R up to 0.9422, p-value <0.001), allowing the simultaneous quantification of several acute phase inflammation proteins. Overall, a proteo-metabolomics NMR signature of significant diagnostic potential is obtained within 10-20 min acquisition time. This is exemplified in serum samples from COVID-19 and cardiogenic shock patients showing significant changes in several acute phase proteins compared to healthy controls.

摘要

人血清和血浆的核磁共振(NMR)谱除了代谢物和脂蛋白外,还显示出两个特征信号,分别称为 GlycA 和 GlycB,它们来自急性相蛋白糖蛋白聚糖的乙酰基,是炎症过程的良好标志物。在这里,我们报告了人血清中观察到的糖蛋白聚糖 NMR 信号的全面分配,表明 GlycA 和 GlycB 信号分别源自 N-聚糖的 Neu5Ac 和 GlcNAc 部分。扩散编辑 NMR 实验表明,信号成分可以与特定的急性相蛋白相关联。传统上确定的急性相糖蛋白浓度与 NMR 谱的明显特征高度相关(R 高达 0.9422,p 值<0.001),允许同时定量几种急性相炎症蛋白。总的来说,在 10-20 分钟的采集时间内获得了具有重要诊断潜力的蛋白代谢组学 NMR 特征。这在 COVID-19 和心源性休克患者的血清样本中得到了例证,与健康对照组相比,这些样本中的几种急性相蛋白发生了显著变化。

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