Figure 1. Peptidomic profiling of synovial fluid from juvenile idiopathic arthritis patients and controls.

(A) Venn diagram reporting the number of endogenous peptides and their protein substrates (peptidomic data are reported in Supplemental Tables 2 and 3) found in the synovial fluid of patients with juvenile idiopathic arthritis (JIA) and controls (data were compiled from 3 separate proteomic analyses). (B) Hierarchical clustering analysis of the protein substrates of the peptidome found in the synovial fluid of patients with JIA and controls was generated in Scaffold 4 using the log of the normalized spectral abundance factor [ln(NSAF)] values [average of 3 experiments for the ln(NSAF)]. The Ward’s dual-clustering method and the t test were performed comparing 2 controls and 7 JIA patients. Only 43 protein substrates of the peptidome were shown to have more than 1.5-fold difference in expression across all patients, with statistical significance corresponding to a FDR < 0.7 [green corresponds to the lowest ln(NSAF), while red corresponds to the highest ln(NSAF)]. The protein substrates with the highest statistically significant contribution to the peptidome of JIA patients versus controls are shown as cluster (I) (at P < 0.08) (peptidomic data used to compile the heat map are reported in Supplemental Table 2F). (C) Analysis of the unique endogenous peptides derived from the degradation of the acute-phase response and cartilage matrix proteins found in the synovial fluid of patients with JIA and controls (data were compiled from 3 separate proteomic analyses). The enhanced degradation of the proteome from the synovial fluid of JIA patients correlates with the increased number of sequenced endogenous peptides. (D) Selected tandem mass spectrometry fragmentation profiles of peptides derived from collagen I (α 1) and from transthyretin, as mapped in the synovial fluid of patients with JIA.