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Updated: Sep 23, 2025
Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
An Artificial Intelligence-guided signature reveals the shared host immune response in MIS-C and Kawasaki disease
Pradipta Ghosh1,2, Gajanan D Katkar3, Chisato Shimizu4,5
1Department of Cellular and Molecular Medicine, University of California San Diego, San Diego, USA. prghosh@ucsd.edu.
Insights
Multisystem inflammatory syndrome in children (MIS-C) and Kawasaki disease (KD) are related inflammatory conditions. MIS-C is more severe, sharing immune pathways but differing in specific cytokine profiles and clinical outcomes.
Area of Science:
- Immunology
- Pediatrics
- Virology
Background:
- Multisystem inflammatory syndrome in children (MIS-C) emerged during the COVID-19 pandemic.
- MIS-C shares clinical features with Kawasaki disease (KD), a pre-pandemic syndrome.
- Understanding the relationship between MIS-C, KD, and COVID-19 is crucial for pediatric health.
Purpose of the Study:
- To compare MIS-C and KD using gene expression signatures.
- To elucidate the shared and distinct immunopathogenesis pathways.
- To identify biomarkers for monitoring MIS-C severity.
Main Methods:
- Utilized viral pandemic (ViP) and severe-ViP gene signatures alongside a KD diagnostic signature.
- Analyzed whole blood RNA sequences, serum cytokines, and cardiac tissues.
- Employed computational analysis to compare gene expression patterns.
Main Results:
- KD and MIS-C lie on a continuum of the immune response to COVID-19.
- Both syndromes exhibit an IL15/IL15RA-centric cytokine storm, indicating shared pathways.
- MIS-C demonstrates unique targetable cytokine pathways and greater severity than KD.
Conclusions:
- MIS-C and KD share immunopathogenesis but diverge in clinical and laboratory parameters.
- ViP signatures differentiate MIS-C severity and identify potential therapeutic targets.
- Clinical indicators like reduced cardiac function, thrombocytopenia, and eosinopenia are key for monitoring MIS-C severity.
Abstract:
Multisystem inflammatory syndrome in children (MIS-C) is an illness that emerged amidst the COVID-19 pandemic but shares many clinical features with the pre-pandemic syndrome of Kawasaki disease (KD). Here we compare the two syndromes using a computational toolbox of two gene signatures that were developed in the context of SARS-CoV-2 infection, i.e., the viral pandemic (ViP) and severe-ViP signatures and a 13-transcript signature previously demonstrated to be diagnostic for KD, and validated our findings in whole blood RNA sequences, serum cytokines, and formalin fixed heart tissues. Results show that KD and MIS-C are on the same continuum of the host immune response as COVID-19. Both the pediatric syndromes converge upon an IL15/IL15RA-centric cytokine storm, suggestive of shared proximal pathways of immunopathogenesis; however, they diverge in other laboratory parameters and cardiac phenotypes. The ViP signatures reveal unique targetable cytokine pathways in MIS-C, place MIS-C farther along in the spectrum in severity compared to KD and pinpoint key clinical (reduced cardiac function) and laboratory (thrombocytopenia and eosinopenia) parameters that can be useful to monitor severity.
