Back to Search
Start Over
Molecular mimicry in multisystem inflammatory syndrome in children.
- Source :
-
Nature [Nature] 2024 Aug; Vol. 632 (8025), pp. 622-629. Date of Electronic Publication: 2024 Aug 07. - Publication Year :
- 2024
-
Abstract
- Multisystem inflammatory syndrome in children (MIS-C) is a severe, post-infectious sequela of SARS-CoV-2 infection <superscript>1,2</superscript> , 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.<br /> (© 2024. The Author(s).)
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 1476-4687
- Volume :
- 632
- Issue :
- 8025
- Database :
- MEDLINE
- Journal :
- Nature
- Publication Type :
- Academic Journal
- Accession number :
- 39112696
- Full Text :
- https://doi.org/10.1038/s41586-024-07722-4