RNAseq based transcriptomics of treatment naive multi inflammatory syndrome in children demonstrates predominant activation of matrisome innate and humoral immune pathways

MISC is a rare highly inflammatory state resembling incomplete Kawasaki disease temporarily associated with COVID19 The pathogenesis is not completely known RNAseq was carried out on whole blood of six treatment naive MISC patients This was compared against RNAseq transcriptomics data of five healthy controls four Kawasaki Disease and seven systemic Juvenile Idiopathic Arthritis Using PCA MISC clustered separately from HC KD and sJIA Amongst the top 50 significant genes in the three comparisons with HC KD and sJIA common genes were TMCC2 ITGA2B DMTN GFI1B PF4 QSER1 GRAP2 TUBB1 DSEA revealed that maximum number of hits for overexpressed pathways was for NABA matrisome activation when MISC was compared against HC Cytokine stimulated cellular activation pathways specifically IL10 were downregulated MIS-C had more activated pathways of neutrophil degranulation and acquired immune activation but less of coagulation system or heat shock system involvement as compared to KD As compared to sJIA humoral immune response and complements were activated Matrisome activation was higher with increased cell cell interaction and ECM signalling This analysis revealed novel insights into the pathogenesis of MISC including the potential role of matrisomes humoral immune system and down-regulated interleukin10 pathways