Immune dysregulation and autoreactivity correlate with disease severity in SARS-CoV-2-associated multisystem inflammatory syndrome in children
| Autor: | Andrew J. Rice, Alamzeb Khan, Ningshan Li, Charles S. Dela Cruz, Xiting Yan, Kenneth B. Hoehn, Hiromitsu Asashima, Victoria Habet, Tomokazu Sumida, Jason Bishai, Merrick Lopez, Carrie L. Lucas, Jason Catanzaro, Brian Sellers, John S. Tsang, Pamela A. Guerrerio, David van Dijk, Michela Comi, Richard W. Pierce, Anjali Ramaswamy, Harsha K. Chandnani, Zuoheng Wang, Aagam Shah, Avraham Unterman, Yunqing Liu, David A. Hafler, Steven H. Kleinstein, Nina N. Brodsky, William W. Lau, Naftali Kaminski, Neha Bansal, Neal G. Ravindra |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Cytotoxicity
Immunologic 0301 basic medicine Myeloid Adolescent Plasma Cells Immunology Receptors Antigen T-Cell Inflammation MIS-C plasmablasts CD8-Positive T-Lymphocytes Biology medicine.disease_cause Severity of Illness Index Asymptomatic Article Autoimmunity 03 medical and health sciences 0302 clinical medicine Severity of illness medicine otorhinolaryngologic diseases Humans Immunology and Allergy Myeloid Cells Endothelium Child Autoantibodies SARS-CoV-2 alarmins TRBV11-2 T-cell receptor COVID-19 Immune dysregulation Systemic Inflammatory Response Syndrome Killer Cells Natural 030104 developmental biology Infectious Diseases medicine.anatomical_structure pediatric inflammation Child Preschool 030220 oncology & carcinogenesis cytotoxicity medicine.symptom CD8 |
| Zdroj: | Immunity medRxiv |
| ISSN: | 1097-4180 1074-7613 |
| Popis: | 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. Graphical abstract Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening and unpredictable condition of unknown etiology. Ramaswamy et al. use peripheral blood single-cell transcriptomic profiling along with other techniques to define key innate and adaptive signatures that characterize MIS-C. |
| Databáze: | OpenAIRE |
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