Untargeted metabolomics reveals novel serum biomarker of renal damage in rheumatoid arthritis
Untargeted metabolomics reveals novel serum biomarker of renal damage in rheumatoid arthritis
复制标题
非靶向代谢组学揭示类风湿性关节炎肾损伤的新型血清生物标志物
DOI：
10.1016/j.jpba.2019.113068
复制
发表时间：
2020-02-20
影响因子：
3.4
通讯作者：
Zhang, Yanjun
中科院分区：
文献类型：
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作者：
Song, Lili;Yin, Qingsheng;Zhang, Yanjun
类风湿关节炎(RA)是一种慢性进行性疾病，常累及肾、肺、心等系统。肾损害在类风湿关节炎中相当常见。探讨RA进展过程中肾脏损害的生物标志物对疾病的诊断和治疗具有重要意义。采用II型胶原诱导性关节炎(CIA)模型。分别于初次免疫后第4、6、8、10周采集血清。建立了一种基于UPLC-QJTOF/MS和支持向量机的非靶向代谢组学策略，以发现RA阶段(RA模型中4~6周，此时肾脏不受影响)和RA阶段(RA模型中8~10周，肾脏受影响)大鼠血清中的生物标志物。用主成分分析(PCA)和正交偏最小二乘判别分析(OPLS-DA)分析大鼠血清的代谢特征。采用支持向量机方法筛选RA肾损害的特异性标志物。经多因素统计和综合分析，筛选出5个反映RA肾损害的特异性标志物。通过对这些代谢产物的分析，发现戊糖和葡萄糖醛酸间的相互转化与RA肾损害的发病机制密切相关。本研究首次结合CIA模型大鼠不同时相的病理特点，采用非靶向d代谢组学方法。这将为可能合并肾损害的类风湿关节炎患者选择治疗药物提供依据。(C)2019爱思唯尔B.V.保留所有权利。
Rheumatoid arthritis (RA) is a chronic progressive disease, it often involves kidney, lung, heart, and other systems. Renal damage is quite common in RA. Exploring of biomarkers of renal damage in the course of RA progression is of significant importance for disease diagnosis and treatment. We use type II Collagen-Induced Arthritis(CIA) Model. Serums were collected at the 4th, 6th, 8th, and 10th week after the first immunization. An untargeted metabonomic strategy based on UPLC-QJTOF/MS with support vector machine(SVM) was developed to discover the biomarkers in the rats' serum samples between the RA stage(4-6 weeks in RA model, at which time the kidneys are not affected) and renal damage in RA stage(8-10 weeks in RA model, and the kidneys are affected). Principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were used to analyze the metabolic profiles of rat serum. The support vector machine (SVM) method was used to screen the specific markers of renal damage in RA. Following multivariate statistical and integration analysis, 5 specific markers of renal damage in RA were screened and found. After the analysis of these metabolites, pentose and glucuronate interconversions are closely related to the pathogenesis of RA renal damage. The present study first use untargeted dmetabonomics combined with the pathological features in the different phases of CIA model rats. This will provide a basis for the choice of treatment drugs for patients with RA who may be complicated by renal damage. (C) 2019 Elsevier B.V. All rights reserved.