Predicting uveitis onset in children with juvenile idiopathic arthritis

项目摘要 幼年特发性关节炎相关性葡萄膜炎（JIA-U）是一种慢性炎症性眼病， 儿童JIA，并可能导致威胁视力的并发症。儿童定期眼科检查 因为早期葡萄膜炎检测可以预防视觉并发症， 管理我们的长期目标是通过以下措施预防JIA-U患儿威胁视力的眼部损伤： 改善葡萄膜炎的检测和治疗。 这项研究是一项多中心纵向转化研究，是专家之间的合作努力， 眼科学、风湿病学、蛋白质组学、分析开发、遗传学和生物统计学。的目标 这项研究的目的是：1）描述泪液中的生物标志物谱，以识别JIA-U风险增加的儿童，2） 在JIA儿童中识别早期葡萄膜炎诊断的遗传风险因素，3）发展葡萄膜炎风险 估计整合人口统计学，临床因素，JIA-U生物标志物和遗传变异。我们将招收 对250名最近诊断为JIA的儿童进行前瞻性随访，这些儿童没有葡萄膜炎的临床证据。 将在一系列时间点比较JIA-U儿童和未患JIA-U儿童的生物标志物水平 发展葡萄膜炎，以了解窗口的检测。我们还将进行基于SNP的遗传关联 包括750名JIA儿童（无葡萄膜炎）和750名JIA-U儿童的研究，以确定 与生物标志物水平有关，也与眼病的遗传易感性有关。采用综合方法， 考虑到临床，生物学和遗传因素，我们将产生一个葡萄膜炎的风险估计， 儿童患眼疾的风险增加。我们希望这种新工具在疾病早期的应用将允许 早期干预和改善视力的结果。

PROJECT SUMMARY Juvenile idiopathic arthritis-associated uveitis (JIA-U) is a chronic inflammatory eye disease that affects 20% of children with JIA and can lead to sight-threatening complications. Regular ophthalmic screening of children with JIA is crucial because early uveitis detection can prevent visual complications and influence therapeutic management. Our long-term goal is to prevent sight-threatening ocular damage in children with JIA-U by improving uveitis detection and treatment. This investigation is a multi-site longitudinal translational study that is a collaborative effort between experts in ophthalmology, rheumatology, proteomics, assay development, genetics, and biostatistics. The objectives of this study are to: 1) Delineate a biomarker profile in tears that identifies children at increased risk for JIA-U, 2) Identify genetic risk factors for early uveitis diagnosis among children with JIA, and 3) Develop a uveitis risk estimator integrating demographics, clinical factors, JIA-U biomarkers, and genetic variations. We will enroll 250 children with recently diagnosed JIA, without clinical evidence of uveitis, and follow them prospectively. Levels of biomarkers will be compared at serial time points in children with JIA-U and those who do not develop uveitis to understand the window of detection. We will also conduct SNP-based genetic association studies that include 750 children with JIA (no uveitis) and 750 with JIA-U to identify genetic variations that are related to biomarker levels and also to genetic predilection to eye disease. Using an integrative approach that considers clinical, biological, and genetic factors, we will generate a risk estimator for uveitis that will identify children at elevated risk for eye disease. We expect that application of this new tool early in disease will allow for early intervention and improved vision outcomes.