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鉴定尿CD44和鞘脂激活蛋白原作为神经源性膀胱患儿尿路感染的特异性生物标志物

Identification of Urinary CD44 and Prosaposin as Specific Biomarkers of Urinary Tract Infections in Children With Neurogenic Bladders.

作者信息

Forster Catherine S, Haffey Wendy D, Bennett Michael, Greis Kenneth D, Devarajan Prasad

机构信息

Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

Department of Pediatrics, Children's National Medical Center, Washington, DC, USA.

出版信息

Biomark Insights. 2019 Mar 15;14:1177271919835570. doi: 10.1177/1177271919835570. eCollection 2019.

Abstract

PURPOSE

Distinguishing urinary tract infection (UTI) from urinary tract colonization (UTC) in children with neurogenic bladders who require clean intermittent catheterization (CIC) is challenging. Our objective was to identify urinary proteins to distinguish UTI from UTC in CIC-dependent children that have potential to serve as objective markers of UTI.

EXPERIMENTAL DESIGN

A total of 10 CIC-dependent children were included in the mass spectrometry analysis (UTI = 5, UTC = 5). Quantitative profiling of urine proteins with isobaric protein labeling was performed using tandem mass spectrometry. Candidate markers were normalized using a collective mixture of proteins from all samples. Relative quantitative abundance of proteins across all samples were compared. Proteins with >50% change in the average abundance were identified as proteins of interest, which were then measured using enzyme-linked immunosorbent assay (ELISA) in an additional 40 samples (no growth = 10, UTC = 15, UTI = 15).

RESULTS

Mass spectrometry revealed 8 differentially expressed proteins. Of these, apolipoprotein D, alpha-amylase 2B, non-secretory ribonuclease, CD44 antigen, and prosaposin were measurable by ELISA. Concentrations of both CD44 and prosaposin were significantly higher in UTI, with area under the curves (AUCs) of 0.72 and 0.78, respectively.

CONCLUSION

Urinary CD44 and prosaposin are candidate markers that may assist with the diagnosis of UTI in CIC-dependent children.

摘要

目的

对于需要清洁间歇性导尿(CIC)的神经源性膀胱患儿,区分尿路感染(UTI)和尿路定植(UTC)具有挑战性。我们的目标是鉴定尿蛋白,以区分依赖CIC的儿童的UTI和UTC,这些蛋白有潜力作为UTI的客观标志物。

实验设计

共有10名依赖CIC的儿童纳入质谱分析(UTI = 5,UTC = 5)。使用串联质谱对尿液蛋白进行等压蛋白标记定量分析。候选标志物用所有样本的蛋白质混合液进行标准化。比较所有样本中蛋白质的相对定量丰度。平均丰度变化>50%的蛋白质被鉴定为感兴趣的蛋白质,然后在另外40个样本(无生长 = 10,UTC = 15,UTI = 15)中使用酶联免疫吸附测定(ELISA)进行测量。

结果

质谱分析显示8种差异表达蛋白。其中,载脂蛋白D、α-淀粉酶2B、非分泌型核糖核酸酶、CD44抗原和鞘脂激活蛋白原可用ELISA检测。UTI中CD44和鞘脂激活蛋白原的浓度均显著升高,曲线下面积(AUC)分别为0.72和0.78。

结论

尿CD44和鞘脂激活蛋白原是可能有助于诊断依赖CIC儿童UTI的候选标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cf2/6421595/538758e3044d/10.1177_1177271919835570-fig1.jpg

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