We reasoned that, at least, some of the SJIA urine peptide biomarkers, such as FGA peptide biomarkers, are likely filtered from the circulation into urine. To explore this, we fractionated normal plasma by two-dimensional chroma-tography to extract the naturally occurring peptides for MSMS peptide sequencing. Similar to other plasma peptide direct sequencing efforts [38] , we observed FGA peptide clusters. We found seven FGA peptide clusters in plasma (Electronic Supplementary Table 1) , and our urine peptide biomarkers FGA (20-38) 1,536.69, FGA (605-628) 2,560.2, and FGA (605-629) 2,659.24 were observed in plasma FGA peptide clusters I and VII. We did not detect FGA (605-621) 1,826.80, although this peptide was found in a published plasma peptidome sequencing effort [38] . Urinary peptide FGA (607-622) Table 8 Identification of peptides found in normal plasma that are related to SJIA urine peptide biomarkers previously published one [38] . The urinary FGA peptides found in active SJIA samples (Table 8 ) lack one or two Cterminal residues compared with a related plasma peptide and thus appear to derive from exopeptidase activity. The urinary COL1A1 peptide that is most differentially expressed in active SJIA (Table 8) extends beyond the C terminus of a closely related peptide found in normal plasma, suggesting it may be generated by inhibition of normal protease activity during SJIA. A urinary FGB peptide found in SJIA (at similar levels in KD, but not comparison groups with less systemic inflammation) is identical to a peptide found in normal plasma, suggesting that the precursor protein is increased during inflammation.