Highly neutralizing anti-IFN-ω autoantibodies underlie severe pediatric adenovirus infection.

Neutralizing autoantibodies (auto-Abs) against type I IFNs (IFN-α and IFN-ω) have emerged as major acquired risk factors for severe viral infections. Human adenovirus (HAdV) is highly prevalent in children and can cause severe pneumonia, but the host determinants of disease severity remain poorly understood. We describe here a 5-year-old child with life-threatening HAdV-B7 pneumonia requiring intensive care who carried high-titer anti-IFN-ω auto-Abs of the IgG1 and IgG3 subclasses. Peripheral blood mononuclear cells produced normal amounts of IFN-α and IFN-ω ex vivo; however, IFN-ω was undetectable in the plasma during acute illness. Functional assays demonstrated that the patient's plasma strongly neutralized IFN-ω, abolishing its antiviral signaling and protective effects, resulting in high levels of adenovirus replication and virus-induced cytotoxicity. These findings implicate anti-IFN-ω auto-Abs in severe adenoviral infection and support immunological screening of pediatric patients with unexplained severe viral pneumonia, which may guide targeted management.