Vehof Jelle, Rhee Amber, Rossi Niccolò, Falchi Mario, Hammond Christopher J, Williams Frances M K
Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom; Department of Ophthalmology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Dutch Dry Eye Clinic, Velp, the Netherlands; Department of Ophthalmology, Vestfold Hospital Trust, Tønsberg, Norway.
Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States.
Ocul Surf. 2025 Apr;36:198-208. doi: 10.1016/j.jtos.2025.01.011. Epub 2025 Jan 28.
To test the association between serum inflammatory markers and dry eye disease (DED) using a hypothesis-free proteomic approach in a population-based cohort.
A total of 2602 unselected community-based participants (mean age 61.5 (range 21-92 years), 94.4 % female) from the TwinsUK cohort were examined. DED was assessed with the validated Women's Health Study (WHS) questionnaire; cases were defined by either a previous clinician diagnosis or presence of highly symptomatic dry eye. Serum inflammatory markers were assessed with the Olink Target 96 Inflammation panel. We performed logistic regression mixed effect models, adjusted for age, BMI, sex, and twin relatedness, with false discovery rate (FDR) correction.
Prevalence of WHS-defined DED was 29.1 %, with 26.2 % having a previous diagnosis of DED and 16.5 % having highly symptomatic dry eye. Of 74 inflammatory markers, significant associations with WHS-defined DED were found for neurotrophin-3 (NT-3; OR: 0.68, FDR p-value: 0.043), natural killer-cell receptor 2B4 (CD244; OR: 0.68, FDR p-value: 0.043), C-X-C motif chemokines (CXCL) 9 (OR: 1.23, FDR p-value: 0.043) and CXCL10 (OR: 1.22, FDR p-value: 0.043). Significant association with highly symptomatic dry eye were found with increased levels of CCL19, CXCL9, CXCL10, CCL20, CX3CL1 (fractalkine), TNF, CDCP1, and CCL25.
This large population-based study found several serum inflammatory proteins to be associated with DED, confirming and adding to previous targeted tear and corneal and conjunctival expression studies in murine models and clinic-based case-control studies. Of interest, a novel potential biomarker NT-3, which plays a role in corneal nerve function, was identified.
在一个基于人群的队列中，使用无假设蛋白质组学方法检测血清炎症标志物与干眼病（DED）之间的关联。
对来自英国双胞胎队列的2602名未经过筛选的社区参与者（平均年龄61.5岁（范围21 - 92岁），94.4%为女性）进行检查。使用经过验证的女性健康研究（WHS）问卷评估干眼病；病例定义为既往临床诊断或存在高度症状性干眼。使用Olink Target 96炎症检测板评估血清炎症标志物。我们进行了逻辑回归混合效应模型分析，对年龄、体重指数、性别和双胞胎相关性进行了校正，并采用了错误发现率（FDR）校正。
WHS定义的干眼病患病率为29.1%，其中26.2%既往诊断为干眼病，16.5%有高度症状性干眼。在74种炎症标志物中，发现神经营养因子-3（NT-3；比值比：0.68，FDR p值：0.043）、自然杀伤细胞受体2B4（CD244；比值比：0.68，FDR p值：0.043）、C-X-C基序趋化因子（CXCL）9（比值比：1.23，FDR p值：0.043）和CXCL10（比值比：1.22，FDR p值：0.043）与WHS定义的干眼病存在显著关联。发现CCL19、CXCL9、CXCL10、CCL20、CX3CL1（趋化因子）、TNF、CDCP1和CCL25水平升高与高度症状性干眼存在显著关联。
这项基于大规模人群的研究发现几种血清炎症蛋白与干眼病相关，证实并补充了先前在小鼠模型和基于临床的病例对照研究中针对泪液、角膜和结膜表达的研究。有趣的是，鉴定出一种在角膜神经功能中起作用的新型潜在生物标志物NT-3。
