Immune dysregulation and autoreactivity correlate with disease severity in SARS-CoV-2-associated multisystem inflammatory syndrome in children.
Immunity
; 54(5): 1083-1095.e7, 2021 05 11.
Article
in English
| MEDLINE | ID: covidwho-1179682
ABSTRACT
Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening post-infectious complication occurring unpredictably weeks after mild or asymptomatic SARS-CoV-2 infection. We profiled MIS-C, adult COVID-19, and healthy pediatric and adult individuals using single-cell RNA sequencing, flow cytometry, antigen receptor repertoire analysis, and unbiased serum proteomics, which collectively identified a signature in MIS-C patients that correlated with disease severity. Despite having no evidence of active infection, MIS-C patients had elevated S100A-family alarmins and decreased antigen presentation signatures, indicative of myeloid dysfunction. MIS-C patients showed elevated expression of cytotoxicity genes in NK and CD8+ T cells and expansion of specific IgG-expressing plasmablasts. Clinically severe MIS-C patients displayed skewed memory T cell TCR repertoires and autoimmunity characterized by endothelium-reactive IgG. The alarmin, cytotoxicity, TCR repertoire, and plasmablast signatures we defined have potential for application in the clinic to better diagnose and potentially predict disease severity early in the course of MIS-C.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Systemic Inflammatory Response Syndrome
/
SARS-CoV-2
/
COVID-19
Type of study:
Prognostic study
Limits:
Adolescent
/
Child
/
Child, preschool
/
Humans
Language:
English
Journal:
Immunity
Journal subject:
Allergy and Immunology
Year:
2021
Document Type:
Article
Affiliation country:
J.immuni.2021.04.003
Similar
MEDLINE
...
LILACS
LIS