Single-Cell Meta-Analysis of Neutrophil Activation in Kawasaki Disease and Multisystem Inflammatory Syndrome in Children Reveals Potential Shared Immunological Drivers
Authors' conclusion
Our findings indicate that CD177+ neutrophils may exert systemic pathological damage contributing to the shared morbidities in KD and MIS-C.
Study context
- Population
- Children; single-cell transcriptomic PBMC data
- Participants
- 103 children9 cohorts
- Comparison
- Kawasaki disease (KD) and multisystem inflammatory syndrome in children (MIS-C) vs healthy controls and other pediatric diseases
Methodological detailssingle-cell meta-analysis, 9 cohorts
- Single-cell meta-analysis
- 9 cohorts
Main finding
As reported in the abstract
- Blood signatures associated with CV event risk enriched in KD and MIS-C neutrophils
- Expansion of CD177+ neutrophils with hyperactivated effector functions in KD and MIS-C, not in healthy controls or other pediatric diseases
- KD and MIS-C CD177+ neutrophils had highly similar transcriptomes (conserved damage-related signatures and pathways)
- Shared neutrophil expression program, potentially regulated by SPI1, conferring enhanced effector functions, especially degranulation
- CD177 and shared program expression associated with acute stages; attenuated during KD IVIG treatment and MIS-C recovery
- Shared program associated with coronary and myocardial disorders (disease-gene association analysis)
- TSPO and S100A12 identified and validated as main molecular targets; FDA-approved candidates for repurposing include methotrexate, zaleplon, metronidazole, lorazepam, clonazepam, temazepam, zolpidem
Further findings
Network analysis
- Hub genes correlated with high activation of CD177+ neutrophils
Original publication
Single-Cell Meta-Analysis of Neutrophil Activation in Kawasaki Disease and Multisystem Inflammatory Syndrome in Children Reveals Potential Shared Immunological Drivers. Circulation. Published 31 October 2023. doi:10.
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