Browsing by Author "Vakkilainen, Svetlana"

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    Immunopathological signatures in multisystem inflammatory syndrome in children and pediatric COVID-19
    (2022) Sacco , Keith; Castagnoli , Riccardo; Vakkilainen, Svetlana; Liu, Can; Delmonte, Ottavia M.; Oguz, Cihan; Kaplan, Ian M.; Alehashemi, Sara; Burbelo, Peter D.; Bhuyan, Farzana; Jesus, Adriana A.; Dobbs , Kerry; Rosen, Lindsey B.; Cheng, Aristine; Shaw, Elana; Vakkilainen, Mikko S.; Pala , Francesca; Lack, Justin; Zhang, Yu; Fink, Danielle L.; Oikonomou, Vasileios; Snow , Andrew L.; Dalgard, Clifton L.; Chen, Jinguo; Sellers, Brian A.; Montealegre Sanchez, Gina A.; Barron, Karyl; Rey-Jurado, Emma; Vial, Cecilia; Poli, Cecilia; Licari, Amelia; Montagna, Daniela; Marseglia, Gian Luigi
    Pediatric Coronavirus Disease 2019 (pCOVID-19) is rarely severe; however, a minority of children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might develop multisystem inflammatory syndrome in children (MIS-C), with substantial morbidity. In this longitudinal multi-institutional study, we applied multi-omics (analysis of soluble biomarkers, proteomics, single-cell gene expression and immune repertoire analysis) to profile children with COVID-19 (n= 110) and MIS-C (n= 76), along with pediatric healthy controls (pHCs; n= 76). pCOVID-19 was characterized by robust type I interferon (IFN) responses, whereas prominent type II IFN-dependent and NF-κB-dependent signatures, matrisome activation and increased levels of circulating spike protein were detected in MIS-C, with no correlation with SARS-CoV-2 PCR status around the time of admission. Transient expansion of TRBV11-2 T cell clonotypes in MIS-C was associated with signatures of inflammation and T cell activation. The association of MIS-C with the combination of HLA A*02, B*35 and C*04 alleles suggests genetic susceptibility. MIS-C B cells showed higher mutation load than pCOVID-19 and pHC. These results identify distinct immunopathological signatures in pCOVID-19 and MIS-C that might help better define the pathophysiology of these disorders and guide therapy

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