tetano
Editor, Senior Moderator
Nature
. 2024 Aug 7.
doi: 10.1038/s41586-024-07722-4. Online ahead of print. Molecular mimicry in multisystem inflammatory syndrome in children
Aaron Bodansky[SUP] #[/SUP][SUP] 1 [/SUP], Robert C Mettelman[SUP] #[/SUP][SUP] 2 [/SUP], Joseph J Sabatino Jr[SUP] 3 4 [/SUP], Sara E Vazquez[SUP] 5 [/SUP], Janet Chou[SUP] 6 7 [/SUP], Tanya Novak[SUP] 8 9 [/SUP], Kristin L Moffitt[SUP] 7 10 [/SUP], Haleigh S Miller[SUP] 5 11 [/SUP], Andrew F Kung[SUP] 5 11 [/SUP], Elze Rackaityte[SUP] 5 [/SUP], Colin R Zamecnik[SUP] 3 4 [/SUP], Jayant V Rajan[SUP] 5 [/SUP], Hannah Kortbawi[SUP] 5 12 [/SUP], Caleigh Mandel-Brehm[SUP] 5 [/SUP], Anthea Mitchell[SUP] 13 [/SUP], Chung-Yu Wang[SUP] 13 [/SUP], Aditi Saxena[SUP] 13 [/SUP], Kelsey Zorn[SUP] 5 [/SUP], David J L Yu[SUP] 14 [/SUP], Mikhail V Pogorelyy[SUP] 2 [/SUP], Walid Awad[SUP] 2 [/SUP], Allison M Kirk[SUP] 2 [/SUP], James Asaki[SUP] 15 [/SUP], John V Pluvinage[SUP] 4 [/SUP], Michael R Wilson[SUP] 3 4 [/SUP], Laura D Zambrano[SUP] 16 [/SUP], Angela P Campbell[SUP] 16 [/SUP]; Overcoming COVID-19 Network Investigators; Paul G Thomas[SUP] 2 [/SUP], Adrienne G Randolph[SUP] 7 8 9 [/SUP], Mark S Anderson[SUP] 17 18 [/SUP], Joseph L DeRisi[SUP] 19 20 [/SUP]
Collaborators, Affiliations
Multisystem inflammatory syndrome in children (MIS-C) is a severe, post-infectious sequela of SARS-CoV-2 infection[SUP]1,2[/SUP], 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 Aug 7.
doi: 10.1038/s41586-024-07722-4. Online ahead of print. Molecular mimicry in multisystem inflammatory syndrome in children
Aaron Bodansky[SUP] #[/SUP][SUP] 1 [/SUP], Robert C Mettelman[SUP] #[/SUP][SUP] 2 [/SUP], Joseph J Sabatino Jr[SUP] 3 4 [/SUP], Sara E Vazquez[SUP] 5 [/SUP], Janet Chou[SUP] 6 7 [/SUP], Tanya Novak[SUP] 8 9 [/SUP], Kristin L Moffitt[SUP] 7 10 [/SUP], Haleigh S Miller[SUP] 5 11 [/SUP], Andrew F Kung[SUP] 5 11 [/SUP], Elze Rackaityte[SUP] 5 [/SUP], Colin R Zamecnik[SUP] 3 4 [/SUP], Jayant V Rajan[SUP] 5 [/SUP], Hannah Kortbawi[SUP] 5 12 [/SUP], Caleigh Mandel-Brehm[SUP] 5 [/SUP], Anthea Mitchell[SUP] 13 [/SUP], Chung-Yu Wang[SUP] 13 [/SUP], Aditi Saxena[SUP] 13 [/SUP], Kelsey Zorn[SUP] 5 [/SUP], David J L Yu[SUP] 14 [/SUP], Mikhail V Pogorelyy[SUP] 2 [/SUP], Walid Awad[SUP] 2 [/SUP], Allison M Kirk[SUP] 2 [/SUP], James Asaki[SUP] 15 [/SUP], John V Pluvinage[SUP] 4 [/SUP], Michael R Wilson[SUP] 3 4 [/SUP], Laura D Zambrano[SUP] 16 [/SUP], Angela P Campbell[SUP] 16 [/SUP]; Overcoming COVID-19 Network Investigators; Paul G Thomas[SUP] 2 [/SUP], Adrienne G Randolph[SUP] 7 8 9 [/SUP], Mark S Anderson[SUP] 17 18 [/SUP], Joseph L DeRisi[SUP] 19 20 [/SUP]
Collaborators, Affiliations
- PMID: 39112696
- DOI: 10.1038/s41586-024-07722-4
Multisystem inflammatory syndrome in children (MIS-C) is a severe, post-infectious sequela of SARS-CoV-2 infection[SUP]1,2[/SUP], 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.