Predicting uveitis onset in children with juvenile idiopathic arthritis

预测幼年特发性关节炎儿童葡萄膜炎的发病

• 批准号: 10445255
• 负责人: Sheila Therese Angeles-Han
• 金额: $ 61.9万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-30 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10445255
• 关键词: ATP phosphohydrolase; Adult; Affect; Age; Algorithms; Anterior uveitis; Antinuclear Antibodies; Aqueous Humor; Biological; Biological Markers; Biometry; Blindness; Blood-Retinal Barrier; CCL2 gene; CXCL10 gene; Candidate Disease Gene; Cathepsins; Cells; Characteristics; Child; Childhood; Chronic; Chronic Childhood Arthritis; Clinical; Collection; DNA; Data; Detection; Development; Diagnosis; Disease; Early Diagnosis; Early Intervention; Early identification; Early treatment; Endoplasmic Reticulum; Enrollment; Eye diseases; Future; Genes; Genetic; Genetic Polymorphism; Genetic Risk; Genetic Variation; Genotype; Goals; IL8 gene; Inflammation; Inflammatory; Investigation; Knowledge; Lead; Literature; Logistic Regressions; Measurement; Measures; Modeling; Molecular; Monitor; Nucleic Acid Regulatory Sequences; Ophthalmology; Outcome; Pathogenesis; Pathway interactions; Patients; Population; Predictive Factor; Probability; Proteins; Proteomics; RANTES; Race; Recording of previous events; Reporting; Research; Resources; Rheumatoid Factor; Rheumatology; Risk; Risk Estimate; Risk Factors; Risk Marker; Role; Schedule; Site; Testing; Therapeutic; Time; Uveitis; Validation; Vision; Visual; Visual Acuity; Work; anterior chamber; assay development; base; biomarker panel; chemokine; cohort; complement pathway; cytokine; demographics; genetic association; genetic risk factor; genome-wide; genomic data; health care service utilization; high risk; improved; improved outcome; novel therapeutic intervention; prevent; prospective; rac1 GTP-Binding Protein; risk prediction; risk variant; screening; sex; slit lamp imaging; tool; translational study

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.

项目概要 幼年特发性关节炎相关葡萄膜炎 (JIA-U) 是一种慢性炎症性眼病，影响 20% 患有幼年特发性关节炎的儿童可能会导致危及视力的并发症。定期对儿童进行眼科检查 JIA 至关重要，因为早期葡萄膜炎检测可以预防视力并发症并影响治疗 管理。我们的长期目标是通过以下方式预防 JIA-U 儿童出现威胁视力的眼部损伤： 改善葡萄膜炎的检测和治疗。 这项调查是一项多地点纵向转化研究，是各领域专家之间的合作努力 眼科、风湿病学、蛋白质组学、检测开发、遗传学和生物统计学。的目标 这项研究的目的是：1) 描绘眼泪中的生物标志物概况，以识别 JIA-U 风险增加的儿童，2) 确定幼年特发性关节炎儿童早期葡萄膜炎诊断的遗传风险因素，以及 3) 发展葡萄膜炎风险 估计器整合人口统计、临床因素、JIA-U 生物标志物和遗传变异。我们将报名 研究人员对 250 名最近诊断为 JIA 且没有葡萄膜炎临床证据的儿童进行了前瞻性随访。 将在连续时间点比较患有 JIA-U 的儿童和未患有 JIA-U 的儿童的生物标志物水平 发展葡萄膜炎以了解检测窗口。我们还将进行基于SNP的遗传关联 包括 750 名 JIA（无葡萄膜炎）儿童和 750 名 JIA-U 儿童在内的研究，旨在确定与 与生物标志物水平以及眼部疾病的遗传倾向有关。使用综合方法 考虑临床、生物和遗传因素，我们将生成葡萄膜炎的风险估计器，以识别 儿童患眼病的风险较高。我们期望在疾病早期应用这种新工具将允许 进行早期干预和改善视力结果。