Autoantibodies neutralizing type I IFNs underlie ~5% of herpes simplex encephalitis in adults.
Abstract
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.
// Source
Authors: Julie A. Jensen, Morten Kelder Skouboe, Adrian Gervais, Sofie E. Jørgensen, Nanna Mørk, Marvin Werner, Renée Marije van der Sluis, Bettina Bundgaard, Jacob Bodilsen, Paul Bastard, Muyesier Maimaitili, Stefanie Fruhwürth, Marie Helleberg, Merete Storgaard, Henrik Nielsen, Anne Puel, Shen‐Ying Zhang, Søren R Paludan, Aurélie Cobat, Jean-Laurent Casanova, Trine H Mogensen
Institutions: Rigshospitalet, Inserm, Université Paris Cité, Aalborg University Hospital, Aarhus University, Aarhus University Hospital, Assistance Publique – Hôpitaux de Paris, University of Gothenburg, The University of Texas Southwestern Medical Center, Howard Hughes Medical Institute, Aalborg University, Hôpital Necker-Enfants Malades, Institut des Maladies Génétiques Imagine, Human Genetic of Infectious Diseases