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H NMR 血浆糖蛋白特征分析:类风湿关节炎炎症模式识别的新策略。

Characterization of H NMR Plasma Glycoproteins as a New Strategy To Identify Inflammatory Patterns in Rheumatoid Arthritis.

机构信息

Biosfer Teslab SL; DEEEA, Metabolomics Platform , Universitat Rovira i Virgili, IISPV; CIBERDEM , 43007 Tarragona , Spain.

Unitat de Recerca en Lipids i Arteriosclerosi , Hospital Universitari Sant Joan de Reus; IISPV; CIBERDEM , 43204 Reus , Spain.

出版信息

J Proteome Res. 2018 Nov 2;17(11):3730-3739. doi: 10.1021/acs.jproteome.8b00411. Epub 2018 Oct 24.

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease associated with a high index of morbidity and mortality from cardiovascular diseases. We used H NMR to characterize the plasma glycoprotein and lipoprotein profiles of a cohort of patients with RA ( n = 210) versus healthy individuals ( n = 203) to associate them with the RA disease and its severity. Using H NMR, we developed a line-shape method to characterize the two peaks associated with glycoproteins (GlycA and GlycB) and its derived variables: areas of GlycB (Area GlycB) and GlycA (Area GlycA), shape factors of these two peaks (H/W = height/width), and the distance between them (Distance GlycB-GlycA). We also used the advanced lipoprotein test Liposcale (CE) to characterize the lipoprotein subclasses. The standard lipid panel and traditional inflammatory markers such as C-reactive protein, the erythrocyte sedimentation rate, fibrinogen, the rheumatoid factor, anticitrullinated peptide antibodies, and the DAS28 index have also been determined. RA patients presented a significant 10.65% increase in the GlycA associated area compared with the control group ( p = 2.21 × 10). They also presented significantly higher H/W GlycA and GlycB ratios than the control population (H/W GlycB p = 7.88 × 10; H/W GlycA p = 5.61 × 10). The prediction model that uses the traditional inflammatory variables and the H NMR-derived parameters presented an AUC that was almost 10% higher than the model that only uses the traditional inflammatory variables (from 0.7 to 0.79 AUC). We have demonstrated that GlycA and GlycB variables derived from H NMR, along with classic inflammatory parameters, help to improve the classification of individuals with high RA disease activity.

摘要

类风湿关节炎(RA)是一种慢性自身免疫性炎症性疾病,与心血管疾病的高发病率和死亡率密切相关。我们使用 1H-NMR 对 210 名 RA 患者和 203 名健康对照者的血浆糖蛋白和脂蛋白图谱进行了特征描述,以探讨它们与 RA 疾病及其严重程度的相关性。我们使用 1H-NMR 开发了一种线谱方法来描述与糖蛋白(GlycA 和 GlycB)相关的两个峰及其衍生变量:GlycB 区域(Area GlycB)和 GlycA 区域(Area GlycA)、这两个峰的形状因子(H/W=高度/宽度)以及它们之间的距离(Distance GlycB-GlycA)。我们还使用先进的脂蛋白测试 Liposcale(CE)来描述脂蛋白亚类。还确定了标准脂质谱和传统炎症标志物,如 C 反应蛋白、红细胞沉降率、纤维蛋白原、类风湿因子、抗瓜氨酸肽抗体和 DAS28 指数。与对照组相比,RA 患者的 GlycA 相关区域显著增加了 10.65%(p=2.21×10)。与对照组相比,RA 患者的 GlycA 和 GlycB 的 H/W 比值也显著更高(H/W GlycB p=7.88×10;H/W GlycA p=5.61×10)。使用传统炎症变量和 1H-NMR 衍生参数的预测模型的 AUC 比仅使用传统炎症变量的模型高近 10%(从 0.7 到 0.79 AUC)。我们已经证明,GlycA 和 GlycB 变量源自 1H-NMR,与经典炎症参数一起,有助于提高高 RA 疾病活动个体的分类。

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