University of Bergen, Bergen, Norway.
Arthritis Rheumatol. 2015 Apr;67(4):1084-95. doi: 10.1002/art.39015.
Dependence on invasive procedures for classification of patients with Sjögren's syndrome (SS) hampers timely diagnosis and suitable patient followup. The aim of this study was to recapitulate the diagnosis of SS through noninvasive means and to define the biologic state of SS patients' salivary glands.
Using a 187-plex capture antibody-based assay, salivary proteomic biomarker profiles were generated from patients with primary SS, patients with rheumatoid arthritis, and asymptomatic controls. Discriminant function analyses and Gene Ontology-based network analyses allowed data analyses with a reductionist approach and with a focus on systems biology.
Characterized by significant changes in 61 and 55 proteins, respectively, the salivary proteome of SS patients appeared profoundly altered compared to that of individuals without SS. On this basis, 4-plex and 6-plex biomarker signatures, both including interleukin-4 (IL-4), IL-5, and clusterin, achieved accurate prediction of an individual's group membership for at least 94% of cases. Of note, all misclassified SS patients presented with ectopic germinal center-like structures. Systematic inference of biologic meaning identified SS-related protein patterns delineating B cell-dominated immune responses, macrophage differentiation, and signs of T cell chemotaxis. In addition, proteomic Multi-Analyte Profiles provided insight about proteins related to collagen, cytokine, and growth factor synthesis as well as lipid transport.
The SS-related molecular landscape conveyed by saliva showed great congruence with histopathologic features found in SS and advances understanding of this disease at a molecular level. Such salivary biomarker signatures harbor great potential for improving timeliness of SS diagnosis and enabling suitable patient followup.
对干燥综合征（SS）患者进行分类时依赖有创操作会阻碍及时诊断和适当的患者随访。本研究旨在通过非侵入性手段重新评估 SS 的诊断，并定义 SS 患者唾液腺的生物学状态。
使用基于 187 个捕获抗体的检测方法，从原发性 SS 患者、类风湿关节炎患者和无症状对照者中生成唾液蛋白组生物标志物图谱。判别函数分析和基于基因本体论的网络分析允许采用简化方法和专注于系统生物学的数据分析。
与无 SS 的个体相比，SS 患者的唾液蛋白质组分别表现出 61 种和 55 种蛋白的显著变化，差异极为显著。在此基础上，包含白细胞介素-4（IL-4）、白细胞介素-5（IL-5）和载脂蛋白的 4 plex 和 6plex 生物标志物谱，均能准确预测个体的分组归属，准确率至少为 94%。值得注意的是，所有分类错误的 SS 患者均表现出异位生发中心样结构。对生物学意义的系统推断确定了 SS 相关的蛋白模式，这些模式描述了 B 细胞主导的免疫反应、巨噬细胞分化和 T 细胞趋化的迹象。此外，蛋白组多分析物图谱提供了与胶原、细胞因子和生长因子合成以及脂质转运相关的蛋白的见解。
唾液中传递的 SS 相关分子图谱与 SS 中发现的组织病理学特征具有高度一致性，并在分子水平上推进了对这种疾病的理解。这些唾液生物标志物谱具有提高 SS 诊断及时性和实现适当患者随访的巨大潜力。
