not-yet-known not-yet-known not-yet-known unknown 3.2. Differences in saliva proteome profiles between OFC-positive and OFC-negative group Saliva was collected from all 17 participants, including eight who did not provide consent to serum collection . Six were OFC-positive, and 11 were OFC-negative (Table 1). A total of 8,108 proteins were identified via proteomic analysis of saliva; 7,202 proteins were analyzed after filtering for proteins with at least two detected peptide counts. In subsequent group comparisons, the number of proteins for analysis was filtered to ~6,000 (three times that in serum) to ensure that at least one group contained a minimum of 70% valid values for each protein. In addition to proteome analysis of the serum, we assessed the difference in protein levels between the OFC-positive and OFC-negative groups before OFC (Figure S2). We found significant differences only in 1.1% (65 proteins) of the 6,000 comparable proteins, suggesting that salivary proteome profiles before OFC may not differ between the OFC-positive and OFC-negative groups. Proteins with significantly altered expression 1 and 2 h after OFC compared with before OFC in each group are shown in Figure S6. At 1 h after the OFC, 184 proteins [148 upregulated (Saliva-UpPOS1) and 36 downregulated] in the OFC-positive group (Figure S6A) and 458 proteins [391 upregulated (Saliva-UpNEG1) and 67 downregulated] in the OFC-negative group (Figure S6C) were detected. Contrastingly, 2 h after OFC, 216 proteins [199 upregulated (Saliva-UpPOS2) and 17 downregulated] in the OFC-positive group (Figure S6B) and 49 proteins [31 upregulated (Saliva-UpNEG2) and 18 downregulated] in the OFC-negative group (Figure S6D), were detected. In addition to proteomic analysis of the serum, we performed cluster analysis of enriched ontologies at each time point (Figure S7). Interestingly, terms and pathways including neutrophil degranulation (R-HAS-6798695) and neutrophil extracellular trap formation (KEGG: hsa04613) were shared mainly by the enriched ontologies in Saliva-UpPOS1 and Saliva-UpNEG1, suggesting that pathogenesis, including neutrophil activation, may occur with or without symptom onset. However, we found a difference in terms and pathways between Saliva-UpPOS2 and Saliva-UpNEG2, which included complement and coagulation cascades (KEGG: hsa14610), complement and coagulation (R-HSA-8951664), and positive regulation of cell-substrate adhesion (GO: 0010811). Additionally, the p -value for neutrophil degranulation (R-HAS-6798695) was lower in Saliva-UpPOS2 than in Saliva-UpNEG2.