Anti-DENV IgE correlates with dengue severity and triggers FcεRI-dependent basophil activation inhibited by Omalizumab.

Severe dengue, marked by plasma leakage, is often linked to secondary heterotypic dengue virus (DENV) infection. While mast cells and basophils contribute to dengue pathogenesis, the role of anti-DENV IgE remains unclear. Here, we investigated whether anti-DENV IgE promotes FcεRI-dependent basophil activation, potentially contributing to disease severity. Plasma from dengue fever (DF, n = 42) and dengue hemorrhagic fever (DHF, n = 56) patients, collected at febrile, defervescence, and convalescent phases, were analyzed using an in-house IgE-capture ELISA developed to detect antibodies against all four DENV serotypes. Functional assays employed RS-ATL8, a human FcεRI-expressing basophil reporter cell line, to assess IgE-mediated activation following DENV antigen cross-linking. The anti-IgE monoclonal antibody Omalizumab was used to evaluate FcεRI dependence. Anti-DENV IgE was detected in both DF and DHF, peaking at defervescence and significantly higher in DHF. Total IgE was elevated but did not differ between groups. About one-third of anti-DENV-IgE-positive plasma samples induced RS-ATL8 activation upon DENV challenge, an effect abolished by omalizumab. These findings indicate a potential pathogenic role of anti-DENV IgE and provide a rationale for further investigation of IgE-targeted interventions.