A differential gene expression profiles by cDNA microarrays in endometrioid endometrial carcinoma: a preliminary study

Chung, Min Ji; Chung, Eun Jee; Lee, Taek Hoo; Cho, Young Lae; Park, Il Soo; Lee, Yoon Soon

doi:10.3802/kjgo.2007.18.3.219

Cited by 1 publication

(2 citation statements)

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“…We next determined whether PNMA2's virus-like properties are responsible for eliciting autoantibody production. Since PNMA2 appears to be exclusively expressed in neurons of the CNS (Figure 1b, Supplemental Figure 1), we hypothesize that aberrant expression of PNMA2 in tumor cells (8)(9)(10)(11)(12)37) and release of capsids outside of the CNS may be immunogenic. Virus capsids induce a stronger immune response than soluble proteins due to the capsid's influence on antigen transport, adaptive immune response, and cross-presentation (38)(39)(40)(41).…”

Section: Pnma2 Capsids Induce Autoantibody Productionmentioning

confidence: 99%

“…Patients with elevated levels of PNMA1 (Ma1) or PNMA2 (Ma2) autoantibodies experience limbic/brainstem encephalitis and cerebellar degeneration (5). These patients often present with solid peripheral tumors (1, 6, 7) that are a potential source of PNMA protein (8)(9)(10)(11) and antibodies to PNMA proteins can be diagnostic of specific cancers (12). Prognosis in this paraneoplastic syndrome is poor (7).…”

Section: Introductionmentioning

confidence: 99%

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PNMA2 forms non-enveloped virus-like capsids that trigger paraneoplastic neurological syndrome

Erlendsson

Singh

et al. 2023

Preprint

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Theparaneoplastic 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.PNMAgenes 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 externalspikePNMA2 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 PNMA2spikecapsid epitopes. These observations suggest that PNMA2 capsids released from tumors trigger an autoimmune response that underlies Ma2 paraneoplastic neurological syndrome.

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