Cytotoxic lymphocytes are dysregulated in multisystem inflammatory syndrome in children
Noam D Beckmann,
Phillip H. Comella,
Aviva G. Beckmann,
Nicole W. Simons,
Gabriel E. Hoffman,
Nancy J. Francoeur,
Diane Marie Del Valle,
Jessica Le Berichel,
Lora E. Liharska,
Scott R. Tyler,
Shwetha Hara Sridhar,
The Mount Sinai COVID-19 Biobank Team,
Benjamin S Glicksberg,
Karen M. Wilson,
Marta E. Alarc_n-Riquelme,
Thomas U. Marron,
Adeeb H Rahman,
Bruce D Gelb,
Eric E. Schadt,
Alexander William Charney
Posted 02 Sep 2020
medRxiv DOI: 10.1101/2020.08.29.20182899
Posted 02 Sep 2020
Multisystem inflammatory syndrome in children (MIS-C) presents with fever, inflammation and multiple organ involvement in individuals under 21 years following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To identify genes, pathways and cell types driving MIS-C, we sequenced the blood transcriptomes of MIS-C cases, pediatric cases of coronavirus disease 2019, and healthy controls. We define a MIS-C transcriptional signature partially shared with the transcriptional response to SARS-CoV-2 infection and with the signature of Kawasaki disease, a clinically similar condition. By projecting the MIS-C signature onto a co-expression network, we identified disease gene modules and found genes downregulated in MIS-C clustered in a module enriched for the transcriptional signatures of exhausted CD8+ T-cells and CD56dimCD57+ NK cells. Bayesian network analyses revealed nine key regulators of this module, including TBX21, a central coordinator of exhausted CD8+ T-cell differentiation. Together, these findings suggest dysregulated cytotoxic lymphocyte response to SARS-Cov-2 infection in MIS-C.
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