PNMA2 forms non-enveloped virus-like capsids that trigger paraneoplastic neurological syndrome
The paraneoplastic Ma antigen (PNMA) genes are associated with cancer-induced paraneoplastic syndromes that present with neurological symptoms and autoantibody production. How PNMA proteins trigger a severe autoimmune disease is unclear. PNMA genes are predominately expressed in the central nervous system with little known functions but are ectopically expressed in some tumors. Here, we show that PNMA2 is derived from a Ty3 retrotransposon that encodes a protein which forms virus-like capsids released from cells as non-enveloped particles. Recombinant PNMA2 capsids injected into mice induce a robust autoimmune reaction with significant generation of autoantibodies that preferentially bind external "spike" PNMA2 capsid epitopes, while capsid-assembly-defective PNMA2 protein is not immunogenic. PNMA2 autoantibodies present in cerebrospinal fluid of patients with anti-Ma2 paraneoplastic neurologic disease show similar preferential binding to PNMA2 "spike" capsid epitopes. These observations suggest that PNMA2 capsids released from tumors trigger an autoimmune response that underlies Ma2 paraneoplastic neurological syndrome.
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2023 |
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| Enthalten in: |
bioRxiv : the preprint server for biology - (2023) vom: 09. Feb. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Xu, Junjie [VerfasserIn] |
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Date Revised 16.02.2024 published: Electronic UpdateIn: Cell. 2024 Jan 30;:. - PMID 38301645 Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1101/2023.02.09.527862 |
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| PPN (Katalog-ID): |
NLM353048917 |
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| 500 | |a published: Electronic | ||
| 500 | |a UpdateIn: Cell. 2024 Jan 30;:. - PMID 38301645 | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a The paraneoplastic Ma antigen (PNMA) genes are associated with cancer-induced paraneoplastic syndromes that present with neurological symptoms and autoantibody production. How PNMA proteins trigger a severe autoimmune disease is unclear. PNMA genes are predominately expressed in the central nervous system with little known functions but are ectopically expressed in some tumors. Here, we show that PNMA2 is derived from a Ty3 retrotransposon that encodes a protein which forms virus-like capsids released from cells as non-enveloped particles. Recombinant PNMA2 capsids injected into mice induce a robust autoimmune reaction with significant generation of autoantibodies that preferentially bind external "spike" PNMA2 capsid epitopes, while capsid-assembly-defective PNMA2 protein is not immunogenic. PNMA2 autoantibodies present in cerebrospinal fluid of patients with anti-Ma2 paraneoplastic neurologic disease show similar preferential binding to PNMA2 "spike" capsid epitopes. These observations suggest that PNMA2 capsids released from tumors trigger an autoimmune response that underlies Ma2 paraneoplastic neurological syndrome | ||
| 650 | 4 | |a Preprint | |
| 700 | 1 | |a Erlendsson, Simon |e verfasserin |4 aut | |
| 700 | 1 | |a Singh, Manvendra |e verfasserin |4 aut | |
| 700 | 1 | |a Regier, Matthew |e verfasserin |4 aut | |
| 700 | 1 | |a Ibiricu, Iosune |e verfasserin |4 aut | |
| 700 | 1 | |a Day, Gregory S |e verfasserin |4 aut | |
| 700 | 1 | |a Piquet, Amanda L |e verfasserin |4 aut | |
| 700 | 1 | |a Clardy, Stacey L |e verfasserin |4 aut | |
| 700 | 1 | |a Feschotte, Cedric |e verfasserin |4 aut | |
| 700 | 1 | |a Briggs, John A G |e verfasserin |4 aut | |
| 700 | 1 | |a Shepherd, Jason D |e verfasserin |4 aut | |
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