| Title: |
Evidence of molecular mimicry in multisystem inflammatory syndrome in children (MIS-C) |
| Authors: |
Bodansky, Aaron; Mettelman, Robert; Sabatino, Joseph; Vazquez, Sara; Chou, Janet; Novak, Tanya; Moffitt, Kristin; Miller, Haleigh; Kung, Andrew; Rackaityte, Elze; Zamecnik, Colin; Rajan, Jayant; Kortbawi, Hannah; Mandel-Brehm, Caleigh; Mitchell, Anthea; Wang, Chung-Yu; Saxena, Aditi; Zorn, Kelsey; Yu, David; Pogorelyy, Mikhail; Awad, Walid; Kirk, Allison; Pluvinage, John; Wilson, Michael; Loftis, Laura; Hobbs, Charlotte; Tarquinio, Keiko; Kong, Michelle; Fitzgerald, Julie; Espinal, Paula; Walker, Tracie; Schwartz, Stephanie; Crandall, Hillary; Irby, Katherine; Staat, Mary; Rowan, Courtney; Schuster, Jennifer; Halasa, Natasha; Gertz, Shira; Mack, Elizabeth; Maddux, Aline; Cvijanovich, Natalie; Zinter, Matt; Zambrano, Laura; Campbell, Angela; Thomas, Paul; Randolph, Adrienne; Anderson, Mark; DeRisi, Joseph |
| Source: |
Research Data Catalog |
| Publisher Information: |
UAB Digital Commons |
| Publication Year: |
2024 |
| Subject Terms: |
PhIP-Seq; MIS-C; Molecular mimicry |
| Description: |
Multisystem inflammatory syndrome in children (MIS-C) is a severe, post-infectious sequela of SARS-CoV-2 infection, yet the pathophysiological mechanism connecting the infection to the broad inflammatory syndrome remains unknown. Here we leveraged a large set of MIS-C patient samples (n=199) to identify a distinct set of host proteins that are differentially targeted by patient autoantibodies relative to matched controls. We identified an autoreactive epitope within SNX8, a protein expressed primarily in immune cells that regulates an antiviral pathway associated with MIS-C pathogenesis. In parallel, we also probed the SARS-CoV-2 proteome-wide MIS-C patient antibody response and found it to be differentially reactive to a distinct domain of the SARS-CoV-2 nucleocapsid (N) protein relative to controls. This viral N region and the mapped SNX8 epitope bear remarkable biochemical similarity. Furthermore, we find that many children with anti-SNX8 autoantibodies also have T cells cross-reactive to both SNX8 and this distinct region of the SARS-CoV-2 N protein. Together, these findings suggest that MIS-C patients develop a characteristic immune response against the SARS-CoV-2 N protein that is associated with cross-reactivity to the self-protein SNX8, demonstrating a mechanistic link from the infection to the inflammatory syndrome with implications for better understanding a range of post-infectious autoinflammatory diseases. |
| Document Type: |
text |
| Language: |
unknown |
| Relation: |
https://digitalcommons.library.uab.edu/datasets/135; https://doi.org/10.7272/Q6SJ1HVH |
| DOI: |
10.7272/Q6SJ1HVH |
| Availability: |
https://digitalcommons.library.uab.edu/datasets/135; https://doi.org/10.7272/Q6SJ1HVH |
| Rights: |
https://creativecommons.org/publicdomain/zero/1.0/ |
| Accession Number: |
edsbas.4C2B1606 |
| Database: |
BASE |