GlycA: A Composite Nuclear Magnetic Resonance Biomarker of Systemic Inflammation
GlycA: A Composite Nuclear Magnetic Resonance Biomarker of Systemic Inflammation
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DOI：
10.1373/clinchem.2014.232918
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发表时间：
2015-05-01
影响因子：
9.3
通讯作者：
Tracy, Russell P.
中科院分区：
文献类型：
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作者：
Otvos, James D.;Shalaurova, Irina;Tracy, Russell P.
背景技术背景：在脂蛋白颗粒分析的定量条件下获得的血清的核磁共振（NMR）谱包含可能潜在地用作有用的临床生物标志物的额外信号。我们命名为GlycA的这些信号之一来源于酶促糖基化急性期蛋白上的聚糖N-乙酰葡糖胺残基的子集。我们假设GlycA信号的幅度可能提供一种独特而方便的全身性inflammation.METHODS的测量方法：我们开发了一种光谱去卷积算法，从自动NMR LipoProfile（R）测试光谱中量化GlycA信号幅度，并评估分析。精确度和生物变异性。分析急性期糖蛋白和血清级分的光谱以探测GlycA信号的来源。从动脉粥样硬化多种族研究（梅萨）的5537名参与者的基线血浆的存档NMR LipoProfile光谱中获得的GlycA浓度用于评估与人口统计学和实验室参数（包括炎症测量）的关联。血清GlycA信号的主要急性期蛋白贡献者是α（1）-酸性糖蛋白、触珠蛋白、α（1）-抗胰蛋白酶、α（1）-抗胰凝乳蛋白酶，和转铁蛋白。GlycA浓度与高敏C反应蛋白（hsCRP）（r = 0.56）、纤维蛋白原（r = 0.46）和白细胞介素-6（IL-6）（r = 0.35）相关（均P < 0.0001）。分析不精密度较低在23名健康志愿者中，每周评估一次，持续5周，（超和批间CV分别为1.9%和2.6%）和个体内变异性为4.3%，低于hsCRP（29.2%），胆固醇（5.7%）和甘油三酯结论：GlycA是一种独特的炎症生物标志物，具有分析和临床属性，可以补充或提供优于现有全身性炎症临床标志物的优势。(C)2015年美国临床化学协会
BACKGROUND: Nuclear magnetic resonance (NMR) spectra of serum obtained under quantitative conditions for lipoprotein particle analyses contain additional signals that could potentially serve as useful clinical biomarkers. One of these signals that we named GlycA originates from a subset of glycan N-acetylglucosamine residues on enzymatically glycosylated acute-phase proteins. We hypothesized that the amplitude of the GlycA signal might provide a unique and convenient measure of systemic inflammation.METHODS: We developed a spectral deconvolution algorithm to quantify GlycA signal amplitudes from automated NMR LipoProfile (R) test spectra and assessed analytic. precision and biological variability. Spectra of acute-phase glycoproteins and serum fractions were analyzed to probe the origins of the GlycA signal. GlycA concentrations obtained from archived NMR LipoProfile spectra of baseline plasma from 5537 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) were used to assess associations with demographic and laboratory parameters including measures of inflammation.RESULTS: Major acute-phase protein contributors to the serum GlycA signal are alpha(1)-acid glycoprotein, haptoglobin, alpha(1)-antitrypsin, alpha(1)-antichymotrypsin, and transferrin. GlycA concentrations were correlated with high-sensitivity C-reactive protein (hsCRP) (r = 0.56), fibrinogen (r = 0.46), and interleukin-6 (IL-6) (r = 0.35) (all P < 0.0001). Analytic imprecision was low (ultra- and interassay CVs 1.9% and 2.6%, respectively) and intraindividual variability, assessed weekly for 5 weeks in 23 healthy volunteers, was 4.3%, lower than for hsCRP (29.2%), cholesterol (5.7%), and triglycerides (18.0%).CONCLUSIONS: GlycA is a unique inflammatory biomarker with analytic and clinical attributes that may complement or provide advantages over existing clinical markers of systemic inflammation. (C) 2015 American Association for Clinical Chemistry