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.

中文翻译：

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总剂量定义了由木瓜蛋白酶引起的经皮 IgE/IgG1 介导的速发型超敏反应的发生率

评估人类健康风险需要了解与毒性相关的抗原剂量指标。虽然对迟发型超敏反应的人类健康风险的评估已被了解，但 IgE/IgG1 介导的经皮速发型超敏反应 (ITH) 的指标仍不清楚。在这项工作中，我们旨在研究由 IgE/IgG1 反应介导的经皮 ITH 的剂量指标。木瓜蛋白酶通过人体经皮致敏引起 ITH，被用来致敏豚鼠和小鼠。调整每只动物的总剂量或每单位面积的剂量以了解致敏的驱动因素。木瓜蛋白酶特异性 IgG1 的被动皮肤过敏反应 (PCA) 和酶联免疫吸附试验 (ELISA) 能够量化豚鼠的反应。在小鼠中，使用流式细胞术计算引流淋巴结 (DLN) 中携带抗原的 B 细胞数量，木瓜蛋白酶特异性 IgG1 和 IgE 水平通过 ELISA 定量。PCA 阳性检测率和抗原特异性抗体的数量对应于每只动物的总剂量，而不是每单位面积的剂量。此外，DLN 内吸收抗原的 B 细胞数量也与总剂量相关。这些发现表明总抗原剂量是经皮 IgE/IgG1 介导的 ITH 的重要指标。