Abstract 13544: Inflammasome Activation In Kawasaki Disease And Multisystem Inflammatory Syndrome In Children

Abstract

Introduction: Multisystem Inflammatory Syndrome in Children (MIS-C) is a newly identified syndrome elicited by infection of acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although MIS-C shares several clinical features with Kawasaki disease (KD), a greater magnitude of systemic inflammation is usually associated with MIS-C. Inflammasome activation induces the secretion of pro-inflammatory cytokines, IL-1β and IL-18 and the inflammatory form of cell death, pyroptosis. To provide mechanistic insights into MIS-C and KD, we compared the expression and activation of the inflammasome in blood samples from MIS-C and KD patients. Methods: Expression levels of canonical and non-canonical inflammasome components, including NLRP3 , CASP1 , CASP4 , CASP5 , IL1B , and the inflammatory mediator, TIFA in whole blood from KD and convalescent patients were analyzed from microarray datasets. The expression of these inflammasome-related genes was further examined in whole blood samples from MIS-C, KD, KD shock syndrome (KDSS) and convalescent patients using RT-qPCR. Inflammasome activation and TIFA expression were validated in granulocytes of febrile control, KD and MIS-C patients by Western blotting. Results: TIFA , NLRP3 , CASP1 , CASP4 , CASP5 , IL1B were upregulated in whole blood from MIS-C, KD, and KDSS patients as compared to convalescent patients. However, the differences were not significant among diseases. Although gene expression profiles were similar in KD, KDSS and MIS-C whole blood RNA, the processing of canonical and non-canonical inflammasome caspases, caspase-1, and caspase-4 were only observed in granulocytes isolated from MIS-C patients, but not KD and febrile controls. Moreover, TIFA was upregulated along with the activation of the inflammasome in granulocytes of MIS-C patients. Conclusions: Our results suggest that activation of inflammasomes, especially non-canonical inflammasome induction in granulocytes, is a hallmark of MIS-C, and differentiates it from KD.