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Immunopathological signatures in multisystem inflammatory syndrome in children and pediatric COVID-19 #MMPMID35177862
Sacco K; Castagnoli R; Vakkilainen S; Liu C; Delmonte OM; Oguz C; Kaplan IM; Alehashemi S; Burbelo PD; Bhuyan F; de Jesus AA; Dobbs K; Rosen LB; Cheng A; Shaw E; Vakkilainen MS; Pala F; Lack J; Zhang Y; Fink DL; Oikonomou V; Snow AL; Dalgard CL; Chen J; Sellers BA; Montealegre Sanchez GA; Barron K; Rey-Jurado E; Vial C; Poli MC; Licari A; Montagna D; Marseglia GL; Licciardi F; Ramenghi U; Discepolo V; Lo Vecchio A; Guarino A; Eisenstein EM; Imberti L; Sottini A; Biondi A; Mato S; Gerstbacher D; Truong M; Stack MA; Magliocco M; Bosticardo M; Kawai T; Danielson JJ; Hulett T; Askenazi M; Hu S; Cohen JI; Su HC; Kuhns DB; Lionakis MS; Snyder TM; Holland SM; Goldbach-Mansky R; Tsang JS; Notarangelo LD
Nat Med 2022[May]; 28 (5): 1050-1062 PMID35177862show ga
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-kappaB-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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Nat+Med 2022 ; 28 (5): 1050-1062
