Cytotoxic lymphocytes are dysregulated in multisystem inflammatory syndrome in children
Noam D. Beckmann; Phillip H. Comella; Esther Cheng; Lauren Lepow; Aviva G. Beckmann; Konstantinos Mouskas; Nicole W. Simons; Gabriel E. Hoffman; Nancy J. Francoeur; Diane Marie Del Valle; Gurpawan Kang; Emily Moya; Lillian Wilkins; Jessica Le Berichel; Christie Chang; Robert Marvin; Sharlene Calorossi; Alona Lansky; Laura Walker; Nancy Yi; Alex Yu; Matthew Harnett; Melody Eaton; Sandra Hatem; Hajra Jamal; Alara Akyatan; Alexandra Tabachnikova; Lora E. Liharska; Liam Cotter; Brian Fennessey; Akhil Vaid; Guillermo Barturen; Scott R. Tyler; Hardik Shah; Yinh-chih Wang; Shwetha Hara Sridhar; Juan Soto; Swaroop Bose; Kent Madrid; Ethan Ellis; Elyze Merzier; Konstantinos Vlachos; Nataly Fishman; Manying Tin; Melissa Smith; Hui Xie; Manishkumar Patel; Kimberly Argueta; Jocelyn Harris; Neha Karekar; Craig Batchelor; Jose Lacunza; Mahlet Yishak; Kevin Tuballes; Leisha Scott; Arvind Kumar; Suraj Jaladanki; Ryan Thompson; Evan Clark; Bojan Losic; - The Mount Sinai COVID-19 Biobank Team; Jun Zhu; Wenhui Wang; Andrew Kasarskis; Benjamin S. Glicksberg; Girish Nadkarni; Dusan Bogunovic; Cordelia Elaiho; Sandeep Gangadharan; George Ofori-Amanfo; Kasey Alesso-Carra; Kenan Onel; Karen M. Wilson; Carmen Argmann; Marta E. Alarcón-Riquelme; Thomas U. Marron; Adeeb Rahman; Seunghee Kim-Schulze; Sacha Gnjatic; Bruce D. Gelb; Miriam Merad; Robert Sebra; Eric E. Schadt; Alexander W. Charney.
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| PREPRINT-MEDRXIV | ID: ppmedrxiv-20182899
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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