Total dose defines the incidence of percutaneous IgE/IgG1 mediated immediate-type hypersensitivity caused by papain

Assessment of human health risk requires an understanding of antigen dose metrics associated with toxicity. Whereas assessment of the human health risk for delayed-type hypersensitivity is understood, the metrics remain unclear for percutaneous immediate-type hypersensitivity (ITH) mediated by IgE/IgG1. In this work, we aimed to investigate the dose metric for percutaneous ITH mediated by IgE/IgG1 responses. Papain, which causes ITH via percutaneous sensitization in humans, was used to sensitize guinea pigs and mice. The total dose per animal or dose per unit area was adjusted to understand the drivers of sensitization. Passive cutaneous anaphylaxis (PCA) and enzyme-linked immunosorbent assay (ELISA) for papain-specific IgG1 enabled quantification of the response in guinea pigs. In mice, the number of antigen-bearing B cells in the draining lymph nodes (DLN) was calculated using flow cytometry papain-specific IgG1 and IgE levels were quantified by ELISA. PCA positive test rates and the amounts of antigen-specific antibody corresponded with total dose per animal, not dose per unit area. Furthermore, the number of B cells taking up antigen within DLN also correlated with total dose. These findings indicate that the total antigen dose is the important metric for percutaneous IgE/IgG1-mediated ITH.