Alterations in the Tear Proteome of Dry Eye Patients-A Matter of the Clinical Phenotype
Alterations in the Tear Proteome of Dry Eye Patients-A Matter of the Clinical Phenotype
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DOI：
10.1167/iovs.11-8751
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发表时间：
2013-03-01
影响因子：
4.4
通讯作者：
Grus, Franz H.
中科院分区：
文献类型：
--
作者：
Boehm, Nils;Funke, Sebastian;Grus, Franz H.
目的。先前的研究证实了干眼症患者泪液蛋白质组的改变。本研究的目的是分析考虑不同临床表型的干眼症患者的泪液蛋白模式，以探讨其对泪液膜蛋白组成的影响。我们采用了基于表面增强激光解吸/电离飞行时间(SELDI-TOF)/基质辅助激光解吸/电离飞行时间(MALDI-TOF)/TOF质谱（MS）的策略来检测/鉴定候选生物标志物。研究人员对两项独立研究中169名患者的泪液样本进行了分析。将患者再分为健康对照组（CTRL: N = 39）、缺水性干眼组（DRYaq: N = 40）、脂质缺乏性干眼组（DRYlip: N = 40）和两者合并组（DRYaqlip: N = 40）。我们发现6个肽/蛋白标记符合严格的可靠标记选择标准（两项研究的P < 5.0 -03）。例如，与健康受试者相比，DRYaq和DRYaqlip患者中富含脯氨酸的蛋白4减少。在这些患者中发现Mammaglobin B和lipophilin A以及calgranulin S100A8升高。值得注意的是，DRYlip患者只显示出轻微的变化；这些患者强烈偏离DRYaq或DRYaqlip组。在患者分类方面，我们通过使用6个生物标志物集，实现了对DRYaq和DRYaqlip患者的区分，其敏感性和特异性接近100%（受试者工作特征曲线[ROC曲线]：曲线下面积[AUC] = 1）。本研究表明，干眼症的不同临床表型可以通过泪膜蛋白质组的特定改变来反映。特别是泪膜水相的缺乏似乎强烈地影响了几种蛋白质的表达模式。（中国眼科杂志，2013;54:2385-2392）DOI: 10.1167/iovs.11-8751
PURPOSE. Previous studies demonstrated alterations in the tear proteome of dry eye patients. The aim of the present study was to analyze tear protein patterns of dry eye patients considering different clinical phenotypes in order to examine their influence on tear film protein composition.METHODS. We applied a surface-enhanced laser desorption/ionization-time-of-flight (SELDI-TOF)/matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF)/TOF mass spectrometry (MS)-based strategy to detect/identify candidate biomarkers. Tear samples of 169 patients, enrolled in two independent studies, were analyzed. Patients were subdivided into healthy controls (CTRL: N = 39), aqueous-deficient dry eye (DRYaq: N = 40), lipid-deficient dry eye (DRYlip: N = 40), and a combination of the two (DRYaqlip: N = 40).RESULTS. We uncovered six peptide/protein markers matching the stringent criteria applied for selection of reliable markers (P < 5.0E-03 in both studies). For example, proline-rich protein 4 was found to be diminished in DRYaq and DRYaqlip patients when compared to healthy subjects. Mammaglobin B and lipophilin A were found to be increased in these patients, as well as calgranulin S100A8. Remarkably, DRYlip patients revealed only slight alterations; these patients strongly deviated from the DRYaq or DRYaqlip group. With regard to classification of patients, we achieved discrimination from healthy subjects with a sensitivity and specificity approximate to 100% for DRYaq and DRYaqlip patients (receiver operating characteristic curve [ROC curve]: area under the curve [AUC] = 1) through use of the six-biomarker set.CONCLUSIONS. This study demonstrates that different clinical phenotypes of dry eye are reflected by specific alterations of the tear film proteome. Especially a deficiency of the aqueous phase of the tear film seems to strongly influence the expression patterns of several proteins. (Invest Ophthalmol Vis Sci. 2013; 54: 2385-2392) DOI: 10.1167/iovs.11-8751