Autoantibodies neutralizing type I IFNs in patients with fulminant herpes simplex virus hepatitis

Fulminant viral hepatitis (FVH) is a devastating condition caused by hepatotropic viruses such as hepatitis A virus (HAV), hepatitis B virus (HBV), and HSV-1/2. We studied 149 FVH patients (73 males and 76 females, aged 1-76) for blood autoantibodies (auto-Abs) neutralizing type I interferons (IFNs; IFN-α2, -β, -ω). Six of 16 (37.5%) HSV-triggered FVH patients carried such auto-Abs on admission, including three with a previously known autoimmune disease. These patients contrasted with 133 HAV- (n = 46) or HBV-triggered (n = 87) patients, none of whom had such detectable auto-Abs. Odds ratios for HSV-triggered FVH in individuals with auto-Abs ranged from 35.3 (95% CI: 13.0-96.2; P < 10-7) for those neutralizing only 100 pg/ml IFN-α/ω to 1,895 (CI: 448.5-8,002; P < 10-12) for those neutralizing both IFN-α and IFN-ω at 10 ng/ml. Over one third of HSV-triggered FVH cases in this international cohort were due to preexisting auto-Abs. This finding highlights auto-Abs against type I IFNs as a major determinant of HSV-FVH and paves the way for targeted preventive or therapeutic interventions.

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Publication Details

Journal
The Journal of Experimental Medicine
Published
2025-10-28
DOI
https://doi.org/10.1084/jem.20251760
Citations
4
Primary Topic
Liver Diseases and Immunity
Type
article
Field-Weighted Citation Impact
5.29

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article

Autoantibodies neutralizing type I IFNs in patients with fulminant herpes simplex virus hepatitis

Étienne Javouhey, Paul Bastard, Lorenzo Cavagna, A Haidar et al.
4 citations
The Journal of Experimental Medicine
Liver Diseases and Immunity
5.29
article

Autoantibodies neutralizing type I IFNs in patients with fulminant herpes simplex virus hepatitis

Étienne Javouhey, Paul Bastard, Lorenzo Cavagna, A Haidar, Soraya Boucherit, Sofie E. Jørgensen, Adrian Gervais, Nanna Mørk, Aurélie Cobat, Ahmet Yalçınkaya, Frédèric Gottrand, Nils Landegren, N. Schleinitz, Xiao‐Fei Kong, Jean‐Laurent Casanova, Çiğdem Arıkan, Lucy Bizien, Ahmed Aziz Bousfiha, Dominique Debray, Olivier Bernard, Trine Hyrup Mogensen, Philippe Ichaı̈, Mohamed Bousfiha, Anne Puel, Emmanuelle Jouanguy, Veronica Codullo, William M. Lee, Florence Lacaille, Astrid Marchal, Eric Sandström, Emmanuel Jacquemin, Alessandro Borghesi, Naima Amenzoui, Jody A. Rule, Bertrand Roquelaure, Francesca Trespidi
article en
4 citations

Abstract

Fulminant viral hepatitis (FVH) is a devastating condition caused by hepatotropic viruses such as hepatitis A virus (HAV), hepatitis B virus (HBV), and HSV-1/2. We studied 149 FVH patients (73 males and 76 females, aged 1-76) for blood autoantibodies (auto-Abs) neutralizing type I interferons (IFNs; IFN-α2, -β, -ω). Six of 16 (37.5%) HSV-triggered FVH patients carried such auto-Abs on admission, including three with a previously known autoimmune disease. These patients contrasted with 133 HAV- (n = 46) or HBV-triggered (n = 87) patients, none of whom had such detectable auto-Abs. Odds ratios for HSV-triggered FVH in individuals with auto-Abs ranged from 35.3 (95% CI: 13.0-96.2; P < 10-7) for those neutralizing only 100 pg/ml IFN-α/ω to 1,895 (CI: 448.5-8,002; P < 10-12) for those neutralizing both IFN-α and IFN-ω at 10 ng/ml. Over one third of HSV-triggered FVH cases in this international cohort were due to preexisting auto-Abs. This finding highlights auto-Abs against type I IFNs as a major determinant of HSV-FVH and paves the way for targeted preventive or therapeutic interventions.

The Journal of Experimental MedicineVol. 223(3)
Université Claude Bernard Lyon 1 (FR), University of Geneva (CH), Hôpital Necker-Enfants Malades (FR), Howard Hughes Medical Institute (US), Koç University (TR), Inserm (FR), Aarhus University (DK), Université Paris Cité (FR), Aix-Marseille Université (FR), Université de Lille (FR), University of Pavia (IT), Université Paris-Saclay (FR), Science for Life Laboratory (SE), Hospital for Sick Children (CA), Aarhus University Hospital (DK), Hôpital Femme Mère Enfant (FR), Institut Necker Enfants Malades (FR), Hospital for Sick Children Pediatric Center (US), Assistance Publique Hôpitaux de Marseille (FR), University Hospital Foundation (CA), Southwestern Medical Center (US), Assistance Publique – Hôpitaux de Paris (FR), Hospices Civils de Lyon (FR), University Hospital of Geneva (CH), Institut de Neurosciences de la Timone (FR), Centre Hospitalier Universitaire Ibn Rochd (MA), Policlinico San Matteo Fondazione (IT), Bicêtre Hospital (FR), Hôpital Paul-Brousse (FR), Institut des Maladies Génétiques Imagine (FR), Université Paris 8 (FR), École Polytechnique Fédérale de Lausanne (CH), Geneva College (US), Hacettepe University (TR), Rockefeller University (US), The University of Texas Southwestern Medical Center (US), University of Hassan II Casablanca (MA)
St. Giles Foundation, Fondazione IRCCS Policlinico San Matteo, Fondation du Souffle, Ministère de l'Enseignement supérieur, de la Recherche et de l'Innovation, Institut des maladies génétiques Imagine, Agence Nationale de la Recherche, Institut National de la Santé et de la Recherche Médicale, Fondation pour la Recherche Médicale, Ministero della Salute, Science for Life Laboratory, National Center for Advancing Translational Sciences, CHIST-ERA
Openalex Percentile: Top 3%
Liver Diseases and Immunity
5.29
DOIOpen Access PDFOpenAlex
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