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