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通过临床与代谢组学联合分析鉴定过敏性紫癜性肾炎患儿的生物标志物

Biomarkers identification by a combined clinical and metabonomics analysis in Henoch-Schonlein purpura nephritis children.

作者信息

Sun Lin, Xie Biao, Zhang Qiuju, Wang Yupeng, Wang Xinyu, Gao Bing, Liu Meina, Wang Maoqing

机构信息

Department of Epidemiology and Biostatistics, Public Health College, Harbin Medical University, Harbin, P. R. China.

Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, P. R. China.

出版信息

Oncotarget. 2017 Nov 24;8(69):114239-114250. doi: 10.18632/oncotarget.23207. eCollection 2017 Dec 26.

Abstract

BACKGROUND

In children with Henoch-Schonlein purpura (HSP), the severity of Henoch-Schonlein purpura nephritis (HSPN) is considered responsible for the prognosis of HSP. The pathological process from HSP to HSPN is not clear yet and current diagnostic tools have shortcomings in accurate diagnosis of HSPN. This study aims to assess clinical characteristics of HSP and HSPN, to identify metabolic perturbations involved in HSP progress, and to combine metabolic biomarkers and clinical features into a better prediction for HSPN.

METHODS

A total of 162 children were recruited, including 109 HSP patients and 53 healthy children (HC). The clinical characteristics were compared between HSPN and HSP without nephritis (HSPWN). The serum metabonomics analysis was performed to determine the metabolic differences in HSP and HC.

RESULTS

Among 109 HSP children, 57 progressed to HSPN. The increased D-dimer level was significantly associated with renal damage in HSP. The metabonomic profiles revealed alterations between various subgroups of HSP and HC, making it possible to investigate small-molecule metabolites related to the pathological process of HSP. In total, we identified 9 biomarkers for HSP vs. HC, 7 for HSPWN vs. HC, 9 for HSPN vs. HC, and 3 for HSPN vs. HSPWN.

CONCLUSIONS

(S)-3-hydroxyisobutyric acid, p-Cresol sulfate, and 3-carboxy-4-methyl-5-pentyl-2-furanpropanoic acid were found associated with the progress of HSP to HSPN. Moreover, resulting biomarkers, when combined with D-dimer, allowed improving the HSPN prediction with high sensitivity (94.7%) and specificity (80.8%). Together these findings highlighted the strength of the combination of metabonomics and clinical analysis in the research of HSP.

摘要

背景

在过敏性紫癜(HSP)患儿中,过敏性紫癜性肾炎(HSPN)的严重程度被认为与HSP的预后相关。从HSP到HSPN的病理过程尚不清楚,且目前的诊断工具在准确诊断HSPN方面存在不足。本研究旨在评估HSP和HSPN的临床特征,确定参与HSP进展的代谢紊乱,并将代谢生物标志物和临床特征结合起来,以更好地预测HSPN。

方法

共招募了162名儿童,包括109名HSP患者和53名健康儿童(HC)。比较了HSPN和无肾炎的HSP(HSPWN)之间的临床特征。进行血清代谢组学分析以确定HSP和HC之间的代谢差异。

结果

在109名HSP儿童中,57名进展为HSPN。D - 二聚体水平升高与HSP中的肾损伤显著相关。代谢组学图谱揭示了HSP各亚组与HC之间的差异,使得研究与HSP病理过程相关的小分子代谢物成为可能。我们总共鉴定出9种HSP与HC相比的生物标志物,7种HSPWN与HC相比的生物标志物,9种HSPN与HC相比的生物标志物,以及3种HSPN与HSPWN相比的生物标志物。

结论

发现(S)-3 - 羟基异丁酸、对甲酚硫酸盐和3 - 羧基 - 4 - 甲基 - 5 - 戊基 - 2 - 呋喃丙酸与HSP进展为HSPN相关。此外,所得生物标志物与D - 二聚体结合时,能够以高灵敏度(94.7%)和特异性(80.8%)改善HSPN预测。这些发现共同凸显了代谢组学与临床分析相结合在HSP研究中的优势。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c0b/5768399/2843e0eb2470/oncotarget-08-114239-g001.jpg

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