Classifier training FDR analysis Predictor discovery in training set 4 Training set SJIA (12 F, 12 Q) 1 DIGE raw gel images Matched samples SJIA (10 F, 10 Q) POLY (5 F, 5 Q) Spot finding spot alignment feature extraction Classifier training Classify SJIA F vs Q DIGE analysis Prediction analysis (LDA) Predictor test in testing set 5 Testing set SJIA (10 F, 10 Q) 2 Cluster analysis 2d hierarchical clustering heatmap plotting Normalization manual review Manual review MSMS Protein ID 3 15 protein 2d clustering 12 ELISA Assay development Feature selection 7 Discriminate SJIA F KD FI Supplementary Figure 1 Clustering Box-and-Whisker Analysis Discriminate SJIA F SJIA Q POLY F POLY Q ELISA assays 7 ELISA assay ELISA assay FI (27 ) KD (10) 9 ELISA assay Q->F (5) Q->Q (10) Test to anticipate SJIA F in Q LDA Fisher exact test randomization Blind testing Classify SJIA F vs Q Fisher exact test SJIA F(12) FI (15) Classify SJIA F vs FI Fisher exact test

numberspot label Protein biomarker 11 (a,b)APO-AI 22GSN 33TTR 44FGB 55FGG 66APO-D 77APO-E 88 (a,b)ATIII 99 (a,b)A2M 1010 (a,b)CFH 11 VDB 12 KLKB (a,b)AMBP 14 APO-AIV 15 APO-L 1616 (a,b,c)C (a,b)C9 18 CRP 1919 (a,b,c)HP 20 S100A9 21 S100A (a,b)SAA 23 SAP 24 ACT 25 AGP1 26 C3 Supplementary Figure 2 pH MW/ anti-trypsin 2 albumin 3 serrotransferrin 4 Ig heavy chain 5 Haptoglobin 6 Ig light chain Removed proteins: Patient 1 and Patient 2 whole plasma Patient 1 and Patient 2 after protein depletion AB Hemoglobin

S100A8 /S100A9 Relative DIGE MEASUREMENTS FKDFI SJIA APOA1SAPCRPHPS100A9SAAS100A8A2M Q Supplementary Figure 3 FKDFI SJIA APOA1SAPCRPHPSAAA2M Q Relative ELISA MEASUREMENTS