Autoantibodies neutralizing type I IFNs underlie severe tick-borne encephalitis in ∼10% of patients

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Authors

GERVAIS Adrian MARCHAL Astrid FORTOVA Andrea BERANKOVA Michaela KRBKOVÁ Lenka PÝCHOVÁ Martina SALAT Jiri ZHAO Shuxiang KERROUCHE Nacim TOM Le Voyer STIASNY Karin RAFFL Simon ANNE Schieber Pachart FAFI-KREMER Samira GRAVIER Simon ROBBIANI Davide F ABEL Laurent MACDONALD Margaret R RICE Charles M WEISSMANN Gaia TAREK Kamal Eldin ROBATSCHER Eva ERNE Elke Maria PAGANI Elisabetta BORGHESI Alessandro PUEL Anne BASTARD Paul VELAY Aurelie MARTINOT Martin HANSMANN Yves ABERLE Judith H RUZEK Daniel COBAT Aurelie ZHANG Shen-Ying CASANOVA Jean-Laurent

Year of publication 2024
Type Article in Periodical
Magazine / Source JOURNAL OF EXPERIMENTAL MEDICINE
MU Faculty or unit

Faculty of Medicine

Citation
web https://rupress.org/jem/article/221/10/e20240637/276989/Autoantibodies-neutralizing-type-I-IFNs-underlie
Doi http://dx.doi.org/10.1084/jem.20240637
Keywords Autoantibodies; Type I interferons; Tick-borne encephalitis; Severe disease; Immune response; Neurological infections; Viral encephalitis Patient outcomes; Autoimmunity; Infectious diseases
Attached files
Description Tick-borne encephalitis (TBE) virus (TBEV) is transmitted to humans via tick bites. Infection is benign in >90% of the cases but can cause mild (<5%), moderate (<4%), or severe (<1%) encephalitis. We show here that ~10% of patients hospitalized for severe TBE in cohorts from Austria, Czech Republic, and France carry auto-Abs neutralizing IFN-?2, -ß, and/or -? at the onset of disease, contrasting with only ~1% of patients with moderate and mild TBE. These auto-Abs were found in two of eight patients who died and none of 13 with silent infection. The odds ratios (OR) for severe TBE in individuals with these auto-Abs relative to those without them in the general population were 4.9 (95% CI: 1.5–15.9, P < 0.0001) for the neutralization of only 100 pg/ml IFN-?2 and/or -?, and 20.8 (95% CI: 4.5–97.4, P < 0.0001) for the neutralization of 10 ng/ml IFN-?2 and -?. Auto-Abs neutralizing type I IFNs accounted for ~10% of severe TBE cases in these three European cohorts.
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