The additive effect of IgE-mediated and pseudoallergic hypersensitivity in RBL-2H3 cells and guinea pigs

Drug hypersensitivity reactions (DHR) are commonly observed with various medications. However, some drugs, like Qingkailing (QKL), iodixanol, and vancomycin, previously classified as pseudoallergenic, do not align with clinical observations, creating uncertainty in understanding DHR mechanisms and implementing prevention. In response, our research team hypothesized that IgE-mediated allergy and pseudoallergic hypersensitivity may synergistically lead to more severe reactions. We established an IgE-mediated hypersensitivity model using an anti-dinitrophenyl IgE monoclonal antibody in RBL-2H3 cells and employed ovalbumen (OVA) for guinea pigs. Compound 48/80 served as a positive control for non-immunologic hypersensitivity. We measured β-hexosaminidase and histamine released in cells and guinea pigs to focus on hypersensitivity responses from both IgE-mediated and pseudoallergic pathways. Results indicated that combining pseudoallergenic drugs and IgE significantly increased the hypersensitivity response compared to IgE or separate compound 48/80 groups. This effect was mirrored in the OVA-induced model. Notably, the three pseudoallergic drugs exhibited a similar increase in IgE-mediated hypersensitivity. These findings highlight the additive effects of IgE-mediated and pseudoallergic hypersensitivity, suggesting a more potent DHR response. The study also measured several cytokines and developed a method to differentiate between allergic, pseudoallergic DHRs, and additive reactions, aiding in understanding and controlling serious DHR risks in clinical practice.