The parent proteins of the urine peptide biomarkers can be found in the circulation or kidney. For example, A1AT, FGA, and FGB are all acute-phase plasma proteins, which are synthesized by hepatocytes and megakaryocytes [45] and are found at high levels in the circulation in the setting of acute or chronic inflammation. Increased fibrinogen and fibrin deposition within joints are prominent indicators of active SJIA flare [46] and arthritis [47] . We hypothesize that the SJIA urine peptide biomarkers may result from changes in the concentrations of inflammatory mediators and protein catabolism regulators, altering the levels of peptides that are ultimately filtered into urine or generated in the urinary tract from local protease activity. The consequence is the generation of a disease-specific molecular phenotype in SJIA urine. In support of this model, we and others [38] have found urine FGA peptide biomarkers in plasma. This would suggest that the FGA urine peptide biomarkers are likely to be present in circulation. Future prospective studies are needed to determine whether the plasma A1AT, FGA, and FGB peptides have diagnostic or prognostic value in SJIA disease management. However, UMOD protein is not derived from blood, but is produced by the thick ascending limb of the loop of Henle in kidney. Our plasma analysis failed to find any UMOD peptides, suggesting that UMOD peptide biomarkers are coming from kidney. The differential abundance of UMOD urine peptide biomarkers in SJIA suggests that SJIA is likely to have an impact on normal kidney function. Renal disorders in SJIA patients are not well characterized. One 9-year-old SJIA patient was characterized by an aggressive disease course and developed renal amyloidosis just 2 years after the disease onset [48] . A variety of renal disorders can occur in patients with rheumatoid arthritis (RA), which may due to the underlying disease. The most common disorders associated with RA are membranous nephropathy, secondary amyloidosis, a focal, mesangial proliferative glomerulonephritis, rheumatoid vasculitis, and analgesic nephropathy [49, 50] . It is unclear whether SJIA directly affects renal function or indirectly causes renal inflammation.