Molecular mimicry in multisystem inflammatory syndrome in children.
Nature
; 632(8025): 622-629, 2024 Aug.
Article
en En
| MEDLINE
| ID: mdl-39112696
ABSTRACT
Multisystem inflammatory syndrome in children (MIS-C) is a severe, post-infectious sequela of SARS-CoV-2 infection1,2, 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.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Autoanticuerpos
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Síndrome de Respuesta Inflamatoria Sistémica
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Imitación Molecular
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Reacciones Cruzadas
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SARS-CoV-2
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COVID-19
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Anticuerpos Antivirales
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Epítopos
Idioma:
En
Revista:
Nature
Año:
2024
Tipo del documento:
Article