PNMA2 forms immunogenic non-enveloped virus-like capsids associated with paraneoplastic neurological syndrome. (https://pubmed.ncbi.nlm.nih.gov/38301645/)

These scientists wanted to understand why certain proteins called PNMA proteins are associated with a severe autoimmune disease that affects the nervous system. They found that these PNMA proteins are mostly found in the brain and can also be found in some tumors.

To investigate further, the scientists focused on a specific PNMA protein called PNMA2. They discovered that this protein is actually a part of a virus-like structure called a capsid. Capsids are like little containers that viruses use to protect themselves.

The scientists made copies of the PNMA2 capsids in the lab and injected them into mice. They found that when the mice were injected with the PNMA2 capsids, their immune systems produced special proteins called autoantibodies. These autoantibodies specifically targeted and attached to certain parts of the PNMA2 capsids called "spike" epitopes.

When they looked at the cerebrospinal fluid of patients with the autoimmune disease, they found similar autoantibodies that also specifically targeted the spike epitopes of the PNMA2 capsids.

To see if these PNMA2 capsids could cause any problems in the mice, the scientists tested the mice's learning and memory abilities. They found that the mice injected with PNMA2 capsids had difficulties in learning and memory tasks compared to mice that were not injected.

From these experiments, the scientists concluded that PNMA2 capsids can act as an external antigen, which means they can trigger an immune response in the body that leads to problems in the nervous system. This helps explain why PNMA proteins are associated with the severe autoimmune disease.

Xu J., Erlendsson S., Singh M., Holling GA., Regier M., Ibiricu I., Einstein J., Hantak MP., Day GS., Piquet AL., Smith TL., Clardy SL., Whiteley AM., Feschotte C., Briggs JAG., Shepherd JD. PNMA2 forms immunogenic non-enveloped virus-like capsids associated with paraneoplastic neurological syndrome. Cell. 2024 Jan 30:S0092-8674(24)00011-4. doi: 10.1016/j.cell.2024.01.009.