Protease inhibitor abundance is differentially present in mild and severe EAE mice prior to disease onset, while proteases vary minimally. (A) Two-way ANOVA (n = 4 mice per group) of selected protease abundance in mild and severely scored EAE mice over the course of the study, asterisks denote significance (Dunn’s test corrected *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001). The protease subset selected is representative of the overall trend in protease abundance. (B) Pearson correlation analysis of protease inhibitor abundance and EAE cumulative severity. SERPIN A3M is noted as being significantly correlated, while several others (denoted as ~*) nearly reached significance (p ≤ 0.1, see Supplementary Table 6). Higher EAE score is indicative of greater disease severity (C). Two-way ANOVA of protease inhibitor abundance in mild and severely score EAE mice over time suggested significance between mild and severely affected mice specifically on DPI 3 (Bonferroni corrected, *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001; for complete statistics see Supplementary Table 8).