Gervais et al.
Autoantibodies neutralizing type I IFNs underlie severe tick-borne encephalitis in ∼10% of patients. J Exp Med. 2024; 221(10):e20240637. doi:10.1084/jem.20240637
Recent research has revealed that autoantibodies (auto-Abs) against interferons (IFNs) may contribute to the severity of infectious diseases such as West Nile fever, influenza, and COVID-19. An international team of scientists investigated whether auto-Abs could also play a role in severe forms of tick-borne encephalitis (TBE).
The team examined 441 patients infected with the TBE virus (TBEV) from Austria (177), the Czech Republic (184), France (70), and Italy (10), covering cases with mild, moderate, or severe TBE, to assess the presence of auto-Abs targeting interferons. No auto-Abs were detected in patients with mild or moderate TBE; however, some individuals with severe TBE were found to have neutralizing auto-Abs against IFN-α and/or IFN-ω. Notably, 2 out of 8 patients with severe TBE and auto-Abs died.
The percentage of neutralizing auto-Abs varied across countries, which may be due to differences in the year of infection, the number of hospitalized patients, or the size of the study cohorts.
The prevalence of auto-Abs was significantly higher in patients with severe TBE compared to the general population, and higher concentrations of auto-Abs were linked to more severe disease. In an in-vitro model, Vero-E6 cells infected with the TBE virus showed higher viral titers when incubated with IFN-α, IFN-ω, or serum samples from patients with auto-Abs against these interferons.
Crucially, these auto-Abs were not induced by the TBE virus infection; they were stable over time and not transient. These findings suggest that neutralizing auto-Abs against IFNs may weaken the immune response to the TBE virus. The authors concluded that hospitalized patients with severe TBE might benefit from treatment with IFN-α or IFN-ω to help manage the disease.