Prevalence of neutralizing autoantibodies against type I interferon in dengue patients

The presence of neutralizing autoantibodies (NAbs) against type I IFN (IFN-I) has been associated with severe complications arising from various viral infections. However, the prevalence of IFN-I NAbs in dengue virus (DENV) infection remains unclear. Here, we enrolled 216 hospitalized dengue patients in 2024, including 7 individuals with dengue shock syndrome (DSS) and 42 individuals with dengue hemorrhagic fever (DHF). Utilizing a sensitive luciferase reporter assay, IFN-I NAbs were detected in 7 patients (14.3% of DSS/DHF cases), and their neutralizing ability was further validated in DENV-infected cells. Notably, all NAb-positive patients exhibited plasma leakage tendency and cardiac injury and were significantly older than the overall cohort (75.34 vs. 50.75, P = 0.010). IFN-I NAbs were correlated with clinical parameters of myocardial injury and plasma leakage, with increased odds ratio (OR) for cardiac injury (OR = 22.8, P = 0.003) and hypoproteinemia (OR = 53.5, P = 0.001). These findings suggest that IFN-I NAbs may contribute to severe clinical manifestations of dengue, warranting validation in larger cohorts.