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[用于系统性红斑狼疮生物标志物发现的代谢组学]

[Metabolomics for Biomarker Discovery in Systemic Lupus Erythematosus].

作者信息

Saegusa Jun, Kawano Seiji, Morinobu Akio

出版信息

Rinsho Byori. 2015 Apr;63(4):498-505.

Abstract

Metabolomics is the identification and quantification of the metabolome, all low-molecular-weight metabolites in a biological sample. Cell metabolism is known to have a marked impact on the function of various immune cells. We recently examined the differences in the serum metabolome between patients with systemic lupus erythematosus (SLE) and healthy subjects, using gas chromatography/mass spectrometry (GC/MS), and sought to identify candidates for metabolic biomarkers. We found that the levels of 25 metabolites were significantly different in SLE patients compared to healthy controls. A two-dimensional plot of the principal component analysis scores showed distinct clustering for the two subject groups. Multivariate analysis revealed that variations in the levels of glutamic acid, urea, tyrosine, phosphate and glycerol markedly contributed to the observed separation of metabolomic profiles of the SLE patients and healthy controls. A number of metabolites showed different changes between SLE and rheumatoid arthritis. Furthermore, the serum levels of glutamic acid were significantly correlated with the SLE disease activity index score in the patient group. These findings suggest that GC/MS-based serum metabolomics can serve as a novel diagnostic and monitoring tool for autoimmune diseases, and the pattern of variation in metabolite levels may be useful for understanding the pathophysiology of the diseases and developing novel therapeutic strategies.

摘要

代谢组学是对代谢组(生物样品中所有低分子量代谢物)进行鉴定和定量。已知细胞代谢对各种免疫细胞的功能有显著影响。我们最近使用气相色谱/质谱联用技术(GC/MS)检测了系统性红斑狼疮(SLE)患者与健康受试者血清代谢组的差异,并试图鉴定代谢生物标志物的候选物。我们发现,与健康对照相比,SLE患者中有25种代谢物的水平存在显著差异。主成分分析得分的二维图显示两个受试者组有明显的聚类。多变量分析表明,谷氨酸、尿素、酪氨酸、磷酸盐和甘油水平的变化显著促成了SLE患者与健康对照代谢组学图谱的明显分离。一些代谢物在SLE和类风湿性关节炎之间表现出不同的变化。此外,患者组中谷氨酸的血清水平与SLE疾病活动指数评分显著相关。这些发现表明,基于GC/MS的血清代谢组学可作为自身免疫性疾病的一种新型诊断和监测工具,代谢物水平的变化模式可能有助于理解疾病的病理生理学并制定新的治疗策略。

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