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

This is the authors' abstract. We don't add key points for this paper.

Inborn errors of type I interferon (IFN-I) immunity account for ∼7-8% of herpes simplex encephalitis (HSE) cases in young children, but the pathogenesis of HSE in adults is largely unknown. We report that IFN-I autoantibodies (auto-Abs) in serum/plasma samples drawn before, during, or after HSE in 16/339 Danish adults neutralized 0.1-10 ng/ml of IFN-I. Neutralization was IgG-mediated and was also detected in cerebrospinal fluid in several patients. Patients' serum impaired the ability of exogenous IFN-I to protect fibroblasts against herpes simplex virus (HSV)-1 infection in vitro. Among patients with neutralizing IFN-I auto-Abs, a larger fraction were HSV-1 IgG seronegative, suggesting that these auto-Abs confer a greater risk of HSE during primary HSV-1 infection. Neutralization was mainly driven by auto-Abs to IFN-ω, and the risk of HSE in adults with auto-Abs was significantly elevated (odds ratio [OR] = 3.1 for IFN-ω and OR = 2.0 for any IFN-I) compared with the general population. Overall, auto-Abs neutralizing IFN-I accounted for ∼5% of adult HSE cases.