Abstract 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.