It would have been of interest to assess changes in total protein or peptide excretion in our tested SJIA and contrasting KD/FI samples. Amounts of inflammatory proteins excreted in urine can change dramatically, and febrile states have often been associated with increased protein excretion [51, 52] . Future characterization of the SJIA and KD/FI urine proteomes can help determine whether disease-related changes in total of protein excretion explain the changes in urine peptide profiles we observe in SJIA. Disease-specific alterations of gene transcription in the affected tissue and change in the balance of proteolytic and anti-proteolytic activities in urine, as we have proposed previously [18] , may also contribute to the altered pattern of urine peptides in SJIA. To further explore the possible underlying mechanisms related to urine peptide generation, we used an antibody array with 43 proteins known to be involved in the inflammation of SJIA, including certain proteases and their regulators. Plasma profiling of SJIA flare and quiescent samples using this antibody array identified a biomarker panel of TIMP1, IL-18, RANTES, P-Selectin, MMP9, and L-Selectin, all of which are present at higher abundance in SJIA flare than in quiescence. Given that fibrinogen is a substrate of MMP9 [39] [40] [41] , it is possible that up regulation of MMP9 and TIMP1 in circulation may be directly associated to the generation of FGA peptide biomarkers that ultimately are enriched in urine during active SJIA. It has been shown that treatment of active rheumatoid arthritis with golimumab (human monoclonal antibody to TNF-α) plus methotrexate significantly decreases serum IL-18, E-selectin, TIMP1 and MMP9 levels [53] . IL-18 also has been reported to be a candidate for a key cytokine in the pathogenesis of SJIA [54] . Notably, IL-18 synthesis is increased in SJIA, but not in KD [55] , indicating that there are differences in the inflammatory milieu in these (sometimes clinically similar) diseases. Such differences may explain the differences in expression of the FGA peptide biomarkers in urine between SJIA flare and Kawasaki disease. The observation of P/L-Selectins as part of the plasma biomarker panel suggests that P/L-Selectin-mediated leukocyte migration might be important in SJIA pathogenesis, possibly by mediating the recruitment and/or trafficking of specific leukocyte subtypes into inflammatory foci. Previously analysis [56] of rheumatoid arthritis (RH)-specific collagen breakdown products indicates that RH-specific fragments are formed locally in synovial fluids during diseases process and then released into the circulation. It is likely that the SJIA urine peptide biomarkers, in a similar formation mechanism as RH-specific collagen degradation products, originate due to local inflammation, and then are released in the circulation, which are ultimately enriched and ended in urine.