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

Gervais A, Marchal A, Boucherit S, Abi Haidar A, Bizien L, Yalcinkaya A, Sandström E, Kong XF, Jacquemin E, Bernard O, Debray D, Lacaille F, Ichai P, Arikan C, Javouhey E, Roquelaure B, Gottrand F, Trespidi F, Codullo V, Cavagna L, Schleinitz N, Bousfiha M, Amenzoui N, Bousfiha AA, Jørgensen SE, Mørk N, Mogensen TH, Bastard P, Puel A, Borghesi A, Rule JA, Lee WM, Landegren N, Cobat A, Casanova JL, Jouanguy E

J. Exp. Med. 223 (3) - [2026-03-02; online 2025-12-05]

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.

PubMed 41348319

DOI 10.1084/jem.20251760

Crossref 10.1084/jem.20251760

pmc: PMC12679989
pii: 278554