Correlations of salivary biomarkers with clinical assessments in patients with cystic fibrosis.
Correlations of salivary biomarkers with clinical assessments in patients with cystic fibrosis.
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DOI：
10.1371/journal.pone.0135237
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Walt DR
中科院分区：
文献类型：
--
作者：
Nie S;Zhang H;Mayer KM;Oppenheim FG;Little FF;Greenberg J;Uluer AZ;Walt DR
监测囊性纤维化的临床疾病状态通常需要侵入性收集临床样本。由于其非侵入性收集过程以及与下呼吸道的直接解剖关系，唾液作为囊性纤维化监测的生物液体显示出巨大的潜力。测量人类唾液上清液中多种蛋白质标记物的水平，并研究利用它们为疾病状态提供更定量测量的可能性，用于临床研究和监测囊性纤维化患者。在两个不同的时间点（2010 年和 2013 年）从囊性纤维化患者身上收集和处理全唾液样本，并通过两个单独的平台进行测量。在这项横断面研究中，招募了 71 名参与者的方便样本，并通过多重荧光微阵列（纤维微阵列）测量样本，另外 117 名参与者样本通过自动化即时护理分析仪 (SDReader) 使用基于微球的阵列通过荧光夹心免疫分析进行测量。为了进行比较，分别收集了 56 名和 50 名健康受试者的唾液。对六种目标蛋白的水平进行了定量。在唾液收集当天，还收集了囊性纤维化患者的各种人口统计和临床数据，包括肺活量测定、病史和临床医生的评估。两个平台都观察到了类似的趋势，与健康受试者相比，使用纤维微阵列，囊性纤维化患者的 VEGF、IP-10、IL-8 和 EGF 水平显着升高，MMP-9 水平较低（P ≤ 0.005），而使用 SDReader 时，IP-10、IL-8 水平显着升高，而 MMP-9 和 IL-1β 水平较低（P ≤ 0.02）。六种蛋白质的水平彼此显着相关，在某些情况下，生物标志物水平可用于区分具有不同临床表现的患者亚组。例如，两个平台的 IP-10 水平与 FEV1 和疾病严重程度（由临床医生评估）显着相关（P < 0.05）。唾液上清液中六种蛋白质水平的显着变化，以及这些水平与临床评估的相关性，证明了唾液用于囊性纤维化研究和监测的潜力。
Monitoring clinical disease status in cystic fibrosis frequently requires invasive collection of clinical samples. Due to its noninvasive collection process and direct anatomic relationship with the lower airway, saliva shows great potential as a biological fluid for cystic fibrosis monitoring. To measure the levels of multiple protein markers in human saliva supernatants and investigate the possibility of utilizing them to provide a more quantitative measure of disease state for use in research and monitoring of patients with cystic fibrosis clinically. Whole saliva samples were collected and processed from cystic fibrosis patients at two distinct time points (2010 and 2013) and measured by two separate platforms. In this cross sectional study, a convenience sample of 71 participants were recruited with samples measured by multiplexed fluorescence microarray (fiber microarray) and another 117 participant samples were measured by an automated, point-of-care, analyzer (SDReader) using a microsphere-based array via fluorescence sandwich immunoassay. For comparison, saliva from 56 and 50 healthy subjects were collected, respectively. The levels of six target proteins were quantified. Various demographic and clinical data, including spirometry, medical history, and clinicians’ assessments were also collected from patients with cystic fibrosis on the day of saliva collection. Similar trends were observed with both platforms and compared with healthy subjects, cystic fibrosis patients had significantly elevated levels of VEGF, IP-10, IL-8, and EGF as well as lower levels of MMP-9 (P ≤ 0.005) using fiber microarray and significantly elevated levels of IP-10, IL-8 with lower levels of MMP-9 and IL-1β (P ≤ 0.02) using the SDReader. The levels of the six proteins correlated with each other significantly, and in some cases, biomarker levels could be used to differentiate between subgroups of patients with different clinical presentations. For example, IP-10 levels significantly correlated with FEV1 and disease severity (as evaluated by clinicians) with both platforms (P < 0.05). Significant variations of the levels of six proteins in saliva supernatants, and the correlations of these levels with clinical assessments, demonstrated the potential of saliva for cystic fibrosis research and monitoring.