Systemic Juvenile Idiopathic Arthritis (SJIA) is a rare, auto-inflammatory condition characterized by prolonged synovial inflammation that can lead to structural joint damage. Roughly 15-30% of SJIA patients develop a complication called macrophage activation syndrome (MAS), which is caused by excessive activation and proliferation of T cells along with macrophages. Patients with recurrent MAS can develop interstitial lung disease (LD) with features of pulmonary alveolar proteinosis caused by dysfunction of alveolar macrophages. Once lung disease is diagnosed in children with SJIA, fatality occurs in 57% of patients within two years of diagnosis. Identifying abnormal pathologies that occur early in disease progression and are specific to subtypes of SJIA is imperative in order to improve the standard of care for patients and prolong patient life. Ethos R&D proposes to develop a 2-part assay, consisting of biomarkers related to inflammatory and non-inflammatory pathologies that are perturbed in patients with SJIA, that can be analyzed from urine samples by high-performance liquid chromatography, tandem mass spectrometry (LC-MS/MS). Along with the biomarker assay, Ethos R&D will develop a software-based solution report according to biomarker analysis that will communicate recommended adjuvant therapies for physicians, parents and patients. Through collaboration with clinicians at CCHMC, we will be able to determine the specificity of a urine-based test panel by analyzing subtypes of patients with SJIA (active SJIA, SJIA with MAS, SJIA with lung disease) as compared to healthy controls (patient siblings). Such a technology could provide life-changing standard of care for SJIA patients.
Public Health Relevance Statement: Project Narrative Researchers and physicians from both the drug development community and clinical environment require more understanding of abnormal pathologies associated with systemic juvenile idiopathic arthritis (SJIA) to improve modern standards of care. Utilizing LC-MS/MS methods to identify unique profiles of SJIA provides for rapid, reliable, and scalable techniques that can be implemented in clinical evaluations of patients. By measuring urinary metabolites associated with a specific disorder and adding this information to a multivariate analysis model for each patient, researchers will be able to categorize and treat patients according to objective, biochemical information and improve personalized treatment strategies.
Project Terms: Adjuvant Therapy; Alveolar Macrophages; autoinflammatory; base; Biochemical; Biologic Development; Biological; Biological Assay; Biological Markers; Biological Response Modifier Therapy; biomarker panel; biosignature; Caring; Child; Client; Climacteric; Clinical; Collaborations; Community Developments; Complication; Computer software; Country; cytokine; Data; Development; Diagnosis; Diagnostic; Dietary intake; Disease; Disease Progression; drug development; Environment; Food; Functional disorder; High Pressure Liquid Chromatography; Home environment; hospital laboratories; improved; Individual; Industry; industry partner; Inflammatory; Injections; innovation; instrumentation; Interleukin-1; Interstitial Lung Diseases; joint injury; Kynurenine; Laboratories; Lead; Life; Lung diseases; macrophage; Macrophage activation syndrome; Mass Spectrum Analysis; Measures; Medical; Medical center; Methods; micronutrient deficiency; Micronutrients; Modeling; Modernization; Multivariate Analysis; Nutrient; Nutritional; Parents; Pathology; Patient Care; patient response; patient subsets; Patients; Pattern; Pediatric Hospitals; personalized medicine; Phase; Physicians; Preparation; protein intake; Provider; Pulmonary Alveolar Proteinosis; Recurrence; Relapse; Reporting; research and development; research clinical testing; Research Personnel; response; sample collection; Sampling; Services; Siblings; Small Business Innovation Research Grant; software development; Source; Specificity; standard of care; Structure; success; Synovitis; systemic juvenile idiopathic arthritis; T-Cell Proliferation; tandem mass spectrometry; Technical Expertise; Techniques; Technology; Testing; tool; treatment optimization; treatment response; treatment strategy; urinary; Urine
