1. Molecular mimicry in multisystem inflammatory syndrome in children.
- Author
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Bodansky A, Mettelman RC, Sabatino JJ Jr, Vazquez SE, Chou J, Novak T, Moffitt KL, Miller HS, Kung AF, Rackaityte E, Zamecnik CR, Rajan JV, Kortbawi H, Mandel-Brehm C, Mitchell A, Wang CY, Saxena A, Zorn K, Yu DJL, Pogorelyy MV, Awad W, Kirk AM, Asaki J, Pluvinage JV, Wilson MR, Zambrano LD, Campbell AP, Thomas PG, Randolph AG, Anderson MS, and DeRisi JL
- Subjects
- Child, Humans, Coronavirus Nucleocapsid Proteins chemistry, Coronavirus Nucleocapsid Proteins immunology, Phosphoproteins chemistry, Phosphoproteins immunology, Sorting Nexins chemistry, Sorting Nexins immunology, T-Lymphocytes immunology, Antibodies, Viral immunology, Autoantibodies immunology, COVID-19 immunology, COVID-19 virology, COVID-19 complications, Cross Reactions immunology, Epitopes immunology, Epitopes chemistry, Molecular Mimicry immunology, SARS-CoV-2 chemistry, SARS-CoV-2 immunology, SARS-CoV-2 metabolism, SARS-CoV-2 pathogenicity, Systemic Inflammatory Response Syndrome immunology, Systemic Inflammatory Response Syndrome pathology, Systemic Inflammatory Response Syndrome virology
- Abstract
Multisystem inflammatory syndrome in children (MIS-C) is a severe, post-infectious sequela of SARS-CoV-2 infection
1,2 , yet the pathophysiological mechanism connecting the infection to the broad inflammatory syndrome remains unknown. Here we leveraged a large set of samples from patients with MIS-C to identify a distinct set of host proteins targeted by patient autoantibodies including a particular autoreactive epitope within SNX8, a protein involved in regulating an antiviral pathway associated with MIS-C pathogenesis. In parallel, we also probed antibody responses from patients with MIS-C to the complete SARS-CoV-2 proteome and found enriched reactivity against a distinct domain of the SARS-CoV-2 nucleocapsid protein. The immunogenic regions of the viral nucleocapsid and host SNX8 proteins bear remarkable sequence similarity. Consequently, we found that many children with anti-SNX8 autoantibodies also have cross-reactive T cells engaging both the SNX8 and the SARS-CoV-2 nucleocapsid protein epitopes. Together, these findings suggest that patients with MIS-C develop a characteristic immune response to the SARS-CoV-2 nucleocapsid protein that is associated with cross-reactivity to the self-protein SNX8, demonstrating a mechanistic link between the infection and the inflammatory syndrome, with implications for better understanding a range of post-infectious autoinflammatory diseases., (© 2024. The Author(s).)- Published
- 2024
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