PNMA2 forms immunogenic non-enveloped virus-like capsids associated with paraneoplastic neurological syndrome.
Cell
; 187(4): 831-845.e19, 2024 Feb 15.
Article
em En
| MEDLINE
| ID: mdl-38301645
ABSTRACT
The paraneoplastic Ma antigen (PNMA) proteins are associated with cancer-induced paraneoplastic syndromes that present with an autoimmune response and neurological symptoms. Why PNMA proteins are associated with this severe autoimmune disease is unclear. PNMA genes are predominantly expressed in the central nervous system and are ectopically expressed in some tumors. We show that PNMA2, which has been co-opted from a Ty3 retrotransposon, encodes a protein that is released from cells as non-enveloped virus-like capsids. Recombinant PNMA2 capsids injected into mice induce autoantibodies that preferentially bind external "spike" PNMA2 capsid epitopes, whereas a capsid-assembly-defective PNMA2 protein is not immunogenic. PNMA2 autoantibodies in cerebrospinal fluid of patients with anti-Ma2 paraneoplastic disease show similar preferential binding to spike capsid epitopes. PNMA2 capsid-injected mice develop learning and memory deficits. These observations suggest that PNMA2 capsids act as an extracellular antigen, capable of generating an autoimmune response that results in neurological deficits.
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Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Síndromes Paraneoplásicas do Sistema Nervoso
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Antígenos de Neoplasias
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Neoplasias
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Proteínas do Tecido Nervoso
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
Cell
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos