Department of Ophthalmology, Baylor College of Medicine, Houston, TX, United States.
Center for Metagenomics and Microbiome Research, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, United States.
Front Immunol. 2021 Jul 19;12:702755. doi: 10.3389/fimmu.2021.702755. eCollection 2021.
Sjögren syndrome (SS) is an autoimmune condition that targets the salivary and lacrimal glands, with cardinal clinical signs of dry eye (keratoconjunctivitis sicca, KCS) and dry mouth. The conjunctiva of SS patients is often infiltrated by immune cells that participate in the induction and maintenance of local inflammation. The purpose of this study was to investigate immune-related molecular pathways activated in the conjunctiva of SS patients. Female SS patients (n=7) and controls (n=19) completed a series of oral, ocular surface exams. Symptom severity scores were evaluated using validated questionnaires (OSDI and SANDE). All patients fulfilled the ACR/EULAR criteria for SS and the criteria for KCS. Fluorescein and lissamine green dye staining evaluated tear-break-up time (TBUT), corneal and conjunctival disease, respectively. Impression cytology of the temporal bulbar conjunctiva was performed to collect cells lysed and subjected to gene expression analysis using the NanoString Immunology Panel. 53/594 differentially expressed genes (DEGs) were observed between SS and healthy controls; 49 DEGs were upregulated, and 4 were downregulated (, and ). The top 10 DEGs in descending order were . Twenty pathways had a global significance score greater or equal to 2. Spearman correlations showed that 29/49 upregulated DEGs correlated with either TBUT (inverse) or OSDI or conjunctival staining score (positive correlations). Venn diagrams identified that 26/29 DEGs correlated with TBUT, 5/26 DEGs correlated with OSDI, and 16/26 correlated with conjunctival staining scores. Five upregulated DEGs () were uniquely negatively correlated with TBUT. These data indicate that the conjunctiva of SS patients exhibits a phenotype of immune activation, although some genes could be inhibitory. Some of the DEGs and pathways overlap with previous DEGs in salivary gland biopsies, but new DEGs were identified, and some of these correlated with symptoms and signs of dry eye. Our results indicate that gene analysis of conjunctiva imprints is a powerful tool to understand the pathogenesis of SS and develop new therapeutic targets.
干燥综合征（SS）是一种自身免疫性疾病，其靶器官为唾液腺和泪腺，主要临床特征为干眼（干燥性角结膜炎，KCS）和口干。SS 患者的结膜常被参与诱导和维持局部炎症的免疫细胞浸润。本研究旨在探讨 SS 患者结膜中激活的免疫相关分子途径。7 名女性 SS 患者（n=7）和 19 名对照者（n=19）完成了一系列口腔、眼表检查。采用经过验证的问卷（OSDI 和 SANDE）评估症状严重程度评分。所有患者均符合 ACR/EULAR 的 SS 标准和 KCS 标准。荧光素和丽丝胺绿染料染色分别评估泪膜破裂时间（TBUT）、角膜和结膜疾病。对颞侧球结膜进行印迹细胞学检查，以收集裂解细胞，并使用 NanoString 免疫组学试剂盒进行基因表达分析。在 SS 患者和健康对照者之间观察到 53/594 个差异表达基因（DEGs）；49 个 DEGs 上调，4 个下调（、和）。按降序排列，前 10 个 DEGs 分别为 、、、、、、、、。有 20 个通路的全局显著性评分大于或等于 2。Spearman 相关性分析显示，29/49 个上调 DEGs 与 TBUT（负相关）或 OSDI 或结膜染色评分（正相关）相关。Venn 图表明，26/29 个 DEGs 与 TBUT 相关，5/26 个 DEGs 与 OSDI 相关，16/26 个 DEGs 与结膜染色评分相关。5 个上调 DEGs（）与 TBUT 呈负相关。这些数据表明，SS 患者的结膜表现出免疫激活的表型，尽管有些基因可能具有抑制作用。一些 DEGs 和通路与唾液腺活检中的先前 DEGs 重叠，但也鉴定到了新的 DEGs，其中一些与干眼的症状和体征相关。我们的结果表明，结膜印迹的基因分析是了解 SS 发病机制和开发新治疗靶点的有力工具。
