Fig. 4: Serum cytokine arrays and whole blood transcriptomes reveal the severity and nature of the cytokine storm in MIS-C that distinguishes it from KD.

a Heatmap displays the results of unsupervised clustering of sub-acute and acute KD (KD-SA, KD-AV; n = 10 each) and MIS-C (n = 10) subjects using the cytokine profiles determined by mesoscale (MSD). Red = cytokines differentially expressed between MIS-C and KD. See also Supplementary Fig. S2 for violin plots for individual cytokines. b Source data are provided as a Supplementary Data 2. Violin plots display the shared (top panels; IL15, MIP1a, IL2, IL6 and VEGF) and distinct (bottom panels; IFNγ, IL1β, IL8, IL10, and TNFα) features of the cytokine storm in MIS-C vs. KD subjects. Statistical significance was determined by one-way ANOVA followed by Tukey’s test for multiple comparisons. c Schematic shows the process used to integrate serum cytokine array results with whole blood RNA Seq data; cytokines that were differentially expressed in MIS-C were used to inform GSEA of the corresponding pathways. d–f Gene set enrichment analysis (GSEA pre-ranked analysis) of three pathways derived from MSigDB: SANA TNF SIGNALING UP (d), TIAN TNF SIGNALING VIA NFkB (e), and SANA RESPONSE TO IFNG UP (f) demonstrate the significance of TNF (d, e) and IFNG (f) pathway activation in MIS-C. g, h Down-regulated genes after IL1B (g) and IL10 (h) stimulation were derived from differential expression analysis of GSE44722 (n = 269 genes), and GSE61298 (n = 208 genes) respectively. GSEA pre-ranked analysis to test the significance of IL1B and IL10 pathway is performed like panels d–f using the down-regulated genes. GSEA pre-ranked analysis computes nominal pvalue and FDR using an empirical phenotype-based permutation test procedure. No adjustments were made for multiple comparisons because of single hypothesis testing. Source data are provided as a Source Data file.