Autoimmune-Associated PTPN22 Variant May Improve Immune Defense Against Covid

A recent study found that a common mutation that’s associated with a higher risk of developing autoimmune diseases is also linked to protection from viral infections. This mutation in the PTPN22 gene is called the PTPN22 1858C>T allele and is found in 5-15% of people in North America. It is considered the highest non-HLA risk allele for autoimmunity. PTPN22 is associated with regulating T cell receptor signaling and regulatory T cells.

To study the role of this mutation in acute infections, the researchers turned to a mouse model where coronavirus infections lead to liver infection and death in half the mice. In mice with the PTPN22 1858C>T allele, they saw that the infected mice had reduced viral titers, lost less weight, and had increased survival compared to mice without the mutant allele.

Digging into the mechanism behind this, the team looked at how the mutation affected a type of immune cell called natural killer cells that normally destroy infected cells. The mice with the PTPN22 1858C>T allele had more mature natural killer cells in the liver and spleen, which could help the mice better fight coronavirus infection.

The current work used a common mouse strain of coronavirus called mouse hepatitis virus (MHV) strain A59, so the researchers plan to test whether the PTPN22 1858C>T allele protects against respiratory viruses like SARS-CoV-2.

Previous work from this group found that mice with this mutation are also protected from chronic viral infections and tumors.

Citations

Barnes, J. R., Shaikh, A. F., Bevis, A. M., Cockerham, T. R., & Orozco, R. C. (2025). Type I interferon production in myeloid cells is regulated by factors independent of Ptpn22. ImmunoHorizons, 9(11), vlaf063. https://doi.org/10.1093/immhor/vlaf063

Bevis, A. M., Rosa, K. J. L. H., Schwarting, N., Cockerham, T. R., Kerr, C. M., More, S., Fehr, A. R., & Orozco, R. C. (2026). An autoimmunity-associated allele of PTPN22 enhances innate antiviral immunity to protect against acute coronavirus infection, Proc. Natl. Acad. Sci., 123(12), e2519903123. https://doi.org/10.1073/pnas.2519903123