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

Autoantibodies neutralizing type I IFNs cause approximately 5% of adult herpes simplex encephalitis cases, mainly targeting IFN-ω.

• Why it matters: Understanding the immune factors behind adult HSE is crucial because inborn errors explain only a small fraction of cases in children, leaving a gap in adult disease mechanisms.
• What they did: The study analyzed serum and cerebrospinal fluid from 339 Danish adults with HSE, identifying that 16 had IgG autoantibodies neutralizing IFN-I, especially IFN-ω, which impaired antiviral responses in vitro.
• The result: Auto-Abs against IFN-ω significantly increased HSE risk (OR=3.1), and their presence accounted for about 5% of adult HSE cases, highlighting a key immune deficiency that could inform targeted therapies.