https://scholars.lib.ntu.edu.tw/handle/123456789/624134
標題: | Immunopathological signatures in multisystem inflammatory syndrome in children and pediatric COVID-19 | 作者: | 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 ARISTINE CHENG 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 |
關鍵字: | APOPTOSIS; DISEASE; IL-33; REPERTOIRE; REVEALS; VACCINE | 公開日期: | 2022 | 出版社: | NATURE PORTFOLIO | 卷: | 28 | 期: | 5 | 起(迄)頁: | 1050 | 來源出版物: | Nature medicine | 摘要: | 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. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/624134 | ISSN: | 1078-8956 | DOI: | 10.1038/s41591-022-01724-3 |
顯示於: | 醫學系 |
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