1. Immune dysregulation and autoreactivity correlate with disease severity in SARS-CoV-2-associated multisystem inflammatory syndrome in children
- Author
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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, and Neal G. Ravindra
- Subjects
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 - 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., 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.
- Published
- 2021