| Title: |
Immunopathological signatures in multisystem inflammatory syndrome in children and pediatric COVID-19 |
| Authors: |
Sacco, K; Castagnoli, R; Vakkilainen, S; Liu, C; Delmonte, O; Oguz, C; Kaplan, I; Alehashemi, S; Burbelo, P; Bhuyan, F; de Jesus, A; Dobbs, K; Rosen, L; Cheng, A; Shaw, E; Vakkilainen, M; Pala, F; Lack, J; Zhang, Y; Fink, D; Oikonomou, V; Snow, A; Dalgard, C; Chen, J; Sellers, B; Montealegre Sanchez, G; Barron, K; Rey-Jurado, E; Vial, C; Poli, M; Licari, A; Montagna, D; Marseglia, G; Licciardi, F; Ramenghi, U; Discepolo, V; Lo Vecchio, A; Guarino, A; Eisenstein, E; Imberti, L; Sottini, A; Biondi, A; Mató, S; Gerstbacher, D; Truong, M; Stack, M; Magliocco, M; Bosticardo, M; Kawai, T; Danielson, J; Hulett, T; Askenazi, M; Hu, S; Cohen, J; Su, H; Kuhns, D; Lionakis, M; Snyder, T; Holland, S; Goldbach-Mansky, R; Tsang, J; Notarangelo, L; Sacco, Keith; Castagnoli, Riccardo; Vakkilainen, Svetlana; Liu, Can; Delmonte, Ottavia M; Oguz, Cihan; Kaplan, Ian M; Alehashemi, Sara; Burbelo, Peter D; Bhuyan, Farzana; de 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, Maria Cecilia; Licari, Amelia; Montagna, Daniela; Marseglia, Gian Luigi; Licciardi, Francesco; Ramenghi, Ugo; Discepolo, Valentina; Lo Vecchio, Andrea; Guarino, Alfredo; Eisenstein, Eli M; Imberti, Luisa; Sottini, Alessandra; Biondi, Andrea; Mató, Sayonara; Gerstbacher, Dana; Truong, Meng; Stack, Michael A; Magliocco, Mary; Bosticardo, Marita; Kawai, Tomoki; Danielson, Jeffrey J; Hulett, Tyler; Askenazi, Manor; Hu, Shaohui; Cohen, Jeffrey I; Su, Helen C; Kuhns, Douglas B; Lionakis, Michail S; Snyder, Thomas M; Holland, Steven M; Goldbach-Mansky, Raphaela; Tsang, John S; Notarangelo, Luigi D |
| Publisher Information: |
Nature Publishing Group country:US 2022 |
| Document Type: |
Electronic Resource |
| Abstract: |
Transcriptomic, proteomic and immune repertoire profiling reveals distinct peripheral features of MIS-C and pediatric COVID-19, including elevated soluble spike protein levels, more pronounced type II IFN-dependent gene expression and a higher B cell mutation rate in patients with MIS-C.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-kappa B-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. |
| Index Terms: |
Child; COVID-19; Human; SARS-CoV-2; Systemic Inflammatory Response Syndrome; T-Lymphocytes; info:eu-repo/semantics/article |
| URL: |
https://hdl.handle.net/10281/476960; info:eu-repo/semantics/altIdentifier/pmid/35177862; info:eu-repo/semantics/altIdentifier/wos/WOS:000757243200002; volume:28; issue:5; firstpage:1050; lastpage:1062; numberofpages:13; journal:NATURE MEDICINE |
| Availability: |
Open access content. Open access content |
| Note: |
STAMPA; English |
| Other Numbers: |
ITBAO oai:boa.unimib.it:10281/476960; 10.1038/s41591-022-01724-3; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85126232677; 1434547232 |
| Contributing Source: |
BICOCCA OPEN ARCH; From OAIster®, provided by the OCLC Cooperative. |
| Accession Number: |
edsoai.on1434547232 |
| Database: |
OAIster |