Autoantibodies neutralizing type I IFNs underlie ~5% of herpes simplex encephalitis in adults.

Autoantibodies neutralizing type I IFNs are linked to approximately 5% of adult herpes simplex encephalitis cases.

• Why it matters: Understanding the causes of HSE in adults is crucial because inborn errors of immunity explain only about 7-8% of cases in children, leaving a significant gap in knowledge about adult cases.
• What they did: The study analyzed serum and cerebrospinal fluid from 339 Danish adults with HSE, identifying that 16 had IgG autoantibodies neutralizing 0.1-10 ng/ml of IFN-I, mainly targeting IFN-ω, which impaired antiviral responses in vitro.
• The result: Auto-Abs against IFN-I, especially IFN-ω, were associated with a significantly increased risk of HSE (OR=3.1 for IFN-ω), and these auto-Abs accounted for about 5% of adult HSE cases, highlighting their role in disease susceptibility.