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An Artificial Intelligence-guided signature reveals the shared host immune response in MIS-C and Kawasaki disease

Author

Listed:
  • Pradipta Ghosh

    (University of California San Diego
    University of California San Diego)

  • Gajanan D. Katkar

    (University of California San Diego)

  • Chisato Shimizu

    (University of California San Diego
    Rady Children’s Hospital-San Diego)

  • Jihoon Kim

    (University of California San Diego)

  • Soni Khandelwal

    (University of California San Diego)

  • Adriana H. Tremoulet

    (University of California San Diego
    Rady Children’s Hospital-San Diego)

  • John T. Kanegaye

    (University of California San Diego
    Rady Children’s Hospital-San Diego)

  • Joseph Bocchini

    (Willis-Knighton Health System)

  • Soumita Das

    (University of California)

  • Jane C. Burns

    (University of California San Diego
    Rady Children’s Hospital-San Diego)

  • Debashis Sahoo

    (University of California San Diego
    University of California San Diego)

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.

Suggested Citation

  • Pradipta Ghosh & Gajanan D. Katkar & Chisato Shimizu & Jihoon Kim & Soni Khandelwal & Adriana H. Tremoulet & John T. Kanegaye & Joseph Bocchini & Soumita Das & Jane C. Burns & Debashis Sahoo, 2022. "An Artificial Intelligence-guided signature reveals the shared host immune response in MIS-C and Kawasaki disease," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30357-w
    DOI: 10.1038/s41467-022-30357-w
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    References listed on IDEAS

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    1. John W. Schoggins & Sam J. Wilson & Maryline Panis & Mary Y. Murphy & Christopher T. Jones & Paul Bieniasz & Charles M. Rice, 2011. "A diverse range of gene products are effectors of the type I interferon antiviral response," Nature, Nature, vol. 472(7344), pages 481-485, April.
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