We are entering an exciting era in pediatric rheumatology. New treatment approaches are improving the lives of children with juvenile idiopathic arthritis (JIA) to such a degree that it's now rare to see wheelchairs or crutches in our waiting rooms. Even splints, commonly used in the past to treat joint contractures, are seldom seen on our patients. Despite our progress, remission in JIA is rare. Recent work by our collaborator, Dr. Carol Wallace, has shown that only 5% of children with the polyarticular JIA (the most severe form of this disease) are in remission 5 years after diagnosis. Part of our problem in achieving remission is that, at the biological level, we don't really understand what """"""""remission"""""""" is. It's a classic case of the difficulty of getting somewhere when you don't really know where you're trying to get. This grant application is about learning where we are trying to get. In this application, we aim to achieve a better understanding of what """"""""remission"""""""" is using microarray-based biomarkers. Research from the Cobb (acute inflammation) and Jarvis (chronic inflammation) laboratories has demonstrated the feasibility of using genome-wide expression profiling can be used to define disease """"""""states"""""""" (e.g., infected vs. not infected;in remission or not in remission). Furthermore, the Jarvis laboratory has demonstrated the promise of using these same technologies to predict clinical outcomes. For each group, these promising preliminary studies must be validated using larger patient populations and prospective study designs. In this application, we propose to validate peripheral blood biomarkers that already suggest that: (1) remission in juvenile arthritis can be identified at the molecular level through distinct gene expression signatures;(2) those signatures include the balance of both pro- and anti- inflammatory gene networks;and (3) the clinical course of children who reach an inactive disease state can be predicted based on molecular signatures that emerge in the peripheral blood mononuclear cells. Furthermore, we will take another step toward clinical application of this work by developing PCR-based whole blood assay to identify the most robust indicators of remission or clinical outcome. This project brings together two experienced investigators from two very different disciplines: pediatric rheumatology (Dr. Jarvis) and surgical intensive care (Dr. Cobb). Furthermore, the project brings together two computational biology groups spanning multiple disciplines, as well as other experienced pediatric rheumatology investigators. Thus, the project is highly responsive to the goals of the most recent NIH roadmap.

Public Health Relevance

This project is aimed at developing biological markers that will allow us to know when children with juvenile idiopathic arthritis have reached remission. We will also develop markers that will allow us to predict the disease course in children who appear to be doing well. Having these markers will be an important part of developing better ways to manage children with this common chronic disease.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Research Project (R01)
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Special Emphasis Panel (ZRG1-MOSS-D (12))
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Wang, Yan Z
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Columbia University (N.Y.)
Schools of Medicine
New York
United States
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Jiang, Kaiyu; Poppenberg, Kerry E; Wong, Laiping et al. (2018) RNA sequencing data from neutrophils of patients with cystic fibrosis reveals potential for developing biomarkers for pulmonary exacerbations. J Cyst Fibros :
Hu, Zihua; Jiang, Kaiyu; Frank, Mark Barton et al. (2018) Modeling Transcriptional Rewiring in Neutrophils Through the Course of Treated Juvenile Idiopathic Arthritis. Sci Rep 8:7805
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Wong, Laiping; Jiang, Kaiyu; Chen, Yanmin et al. (2017) Genetic insights into juvenile idiopathic arthritis derived from deep whole genome sequencing. Sci Rep 7:2657
Wong, Laiping; Jiang, Kaiyu; Chen, Yanmin et al. (2016) Limits of Peripheral Blood Mononuclear Cells for Gene Expression-Based Biomarkers in Juvenile Idiopathic Arthritis. Sci Rep 6:29477
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Hui-Yuen, Joyce S; Zhu, Lisha; Wong, Lai Ping et al. (2016) Chromatin landscapes and genetic risk in systemic lupus. Arthritis Res Ther 18:281
Jiang, Kaiyu; Wong, Laiping; Sawle, Ashley D et al. (2016) Whole blood expression profiling from the TREAT trial: insights for the pathogenesis of polyarticular juvenile idiopathic arthritis. Arthritis Res Ther 18:157
Hu, Zihua; Jiang, Kaiyu; Frank, Mark Barton et al. (2016) Complexity and Specificity of the Neutrophil Transcriptomes in Juvenile Idiopathic Arthritis. Sci Rep 6:27453

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