Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
Electronics and Computer Science, Faculty of Engineering and Physical Sciences, University of Southampton, Southampton, UK.
J Appl Lab Med. 2020 Jan 1;5(1):101-113. doi: 10.1373/jalm.2019.030007.
Systemic inflammation is a marker of ill health and has prognostic implications in multiple health settings. Urinary neopterin is an excellent candidate as a nonspecific marker of systemic inflammation. Expression as urinary neopterin-to-creatinine ratio (UNCR) normalizes for urinary hydration status. Major attractions include (a) urine vs blood sampling, (b) integration of inflammation over a longer period compared with serum sampling, and (c) high stability of neopterin and creatinine.
A high-throughput ultraperformance LC-MS method was developed to measure neopterin and creatinine together from the same urine sample. The assay was applied in several clinical scenarios: healthy controls, symptomatic infections, and multiple sclerosis. Area under the curve was compared between weekly and monthly sampling scenarios. Analysis of a single pooled sample was compared with averaging results from analysis of individual samples.
The assay has excellent intraassay and interassay precision, linearity of dilution, and spike and recovery. Higher UNCR was demonstrated in female vs male individuals, older age, inflammatory disease (multiple sclerosis), and symptomatic infections. In healthy controls, fluctuations in inflammatory state also occurred in the absence of symptomatic infection or other inflammatory triggers. Analysis of a single pooled sample, made up from weekly urine samples, integrates inflammatory activity over time.
UNCR is a useful biomarker of systemic inflammation. The method presented offers simplicity, speed, robustness, reproducibility, efficiency, and proven utility in clinical scenarios. UNCR fluctuations underline the importance of longitudinal monitoring, vs a single time point, to capture a more representative estimate of an individual's inflammatory state over time.
全身性炎症是健康状况不佳的标志，在多种健康环境中具有预后意义。尿中新蝶呤是全身性炎症的非特异性标志物的极佳候选物。尿中新蝶呤与肌酐的比值（UNCR）作为表达形式可使尿液水化状态标准化。主要吸引力包括：（a）尿液与血液采样，（b）与血清采样相比，整合了更长时间段的炎症，以及（c）新蝶呤和肌酐的高稳定性。
开发了一种高通量超高效 LC-MS 方法，可从同一样本尿液中同时测量新蝶呤和肌酐。该测定法应用于几种临床情况：健康对照、有症状的感染和多发性硬化症。比较了每周和每月采样情况的曲线下面积。比较了单个混合样本的分析与对单个样本分析结果的平均值的分析。
该测定法具有出色的日内和日间精密度、线性稀释度以及加标和回收率。与男性相比，女性、年龄较大、炎症性疾病（多发性硬化症）和有症状的感染个体的 UNCR 更高。在健康对照中，即使没有有症状的感染或其他炎症触发，炎症状态也会发生波动。由每周尿液样本组成的单个混合样本的分析可随时间整合炎症活动。
UNCR 是全身性炎症的有用生物标志物。所提出的方法具有简单、快速、稳健、重现性、效率和在临床情况下的实际应用。UNCR 的波动强调了进行纵向监测而非单次时间点监测的重要性，以便更全面地代表个体在一段时间内的炎症状态。
