Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 218, Issue 6, Pages -Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20210446
Keywords
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Categories
Funding
- Howard Hughes Medical Institute
- Rockefeller University
- St. Giles Foundation
- National Institutes of Health [R01AI088364, R01AI148963, R01AI151029, R01AI150300, K08AI135091, R21AI144315-02S1]
- National Center for Advancing Translational Sciences, National Institutes of Health Clinical and Translational Science Award program [UL1 TR001866]
- Yale Center for Mendelian Genomics
- GSP Coordinating Center - National Human Genome Research Institute [UM1HG006504, U24HG008956]
- Institut National de la Sante et de la Recherche Medicale
- Universite de Paris
- French National Research Agency (ANR) Resilience-Covid-19 grant GenMIS-C
- ANR Investments for the Future program [ANR-10-IAHU-01]
- Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence [ANR-10-LABX-62-IBEID]
- ANR project AABIFNCOV [ANR-20-CO11-0001]
- French Foundation for Medical Research [EQU201903007798]
- French Foundation for Medical Research
- ANR GENCOVID project
- ANRSCOV05 project
- Square Foundation
- Grandir - Fonds de solidarite pour l'enfance
- Fondation du Souffle
- SCOR Corporate Foundation for Science
- UK Research and Innovation Future Leader's Fellowship [MR/S032304/1]
- NIHR Imperial Biomedical Research Centre at Imperial College Healthcare NHS Trust [70931]
- Burroughs Wellcome Fund Career Awards for Medical Scientists
- Clinical Immunology Society
- American Academy of Allergy Asthma and Immunology
- Michael Smith Foundation for Health Research
- National Health and Medical Research Council of Australia
- University of New South Wales Sydney COVID Rapid Response Initiative
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MIS-C, a newly emerging syndrome in children associated with COVID-19, shows heterogeneity resembling KD, possibly triggered by viruses and potentially linked to rare inborn errors of immunity altering the immune response. Discovery of monogenic IEIs underlying MIS-C may pave the way for a new genetic approach to classic KD.
Multisystem inflammatory syndrome in children (MIS-C) emerged in April 2020 in communities with high COVID-19 rates. This new condition is heterogenous but resembles Kawasaki disease (KD), a well-known but poorly understood and clinically heterogenous pediatric inflammatory condition for which weak associations have been found with a myriad of viral illnesses. Epidemiological data clearly indicate that SARS-CoV-2 is the trigger for MIS-C, which typically occurs about 1 mo after infection. These findings support the hypothesis of viral triggers for the various forms of classic KD. We further suggest that rare inborn errors of immunity (IEIs) altering the immune response to SARS-CoV-2 may underlie the pathogenesis of MIS-C in some children. The discovery of monogenic IEIs underlying MIS-C would shed light on its pathogenesis, paving the way for a new genetic approach to classic KD, revisited as a heterogeneous collection of IEIs to viruses.
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