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: 10661602
• 负责人: Sheila Therese Angeles-Han
• 金额: $ 62.59万
• 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/10661602
• 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; CXCR3 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; 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; biomarker panel; biomarker validation; 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; ophthalmic examination; 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.

项目摘要 青少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％ Jia的孩子，可能导致危及视力的并发症。定期对儿童进行眼科筛查 与JIA至关重要，因为早期的葡萄膜炎检测可以预防视觉并发症并影响治疗 管理。我们的长期目标是防止JIA-U儿童的视力危害眼睛损害 改善葡萄膜炎的检测和治疗。 这项调查是一项多站点的纵向翻译研究，是专家之间的协作努力 眼科，风湿病学，蛋白质组学，测定开发，遗传学和生物统计学。目标的目标 这项研究是：1）描绘出泪水中的生物标志物概况，以确定jia-u风险增加的儿童，2） 确定JIA儿童早期葡萄膜炎诊断的遗传危险因素，3）出现葡萄膜炎风险 整合人口统计学，临床因素，JIA-U生物标志物和遗传变异的估计量。我们将注册 250名最近被诊断出的JIA的儿童，没有葡萄膜炎的临床证据，并前瞻性地跟随他们。 将在JIA-U和没有的儿童的串行时间点上比较生物标志物的水平 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儿童（无葡萄膜炎）和750名具有JIA-U的研究，以鉴定遗传变异 与生物标志物水平以及对眼病的遗传偏见有关。使用一种综合方法 考虑临床，生物学和遗传因素，我们将为葡萄膜炎产生风险估计量 患有眼病风险较高的儿童。我们希望早期在疾病中使用该新工具将允许 为了早期干预和改善视力结果。