Cincinnati Veterans Affairs Medical Center, Cincinnati, OH 45220, USA.
Proc Natl Acad Sci U S A. 2011 Jul 26;108(30):12413-8. doi: 10.1073/pnas.1105695108. Epub 2011 Jul 11.
IgG-mediated anaphylaxis occurs in mice and may contribute to human reactions to infused drugs. To distinguish IgE- from putative IgG-mediated human anaphylaxis, we developed blood markers for murine anaphylaxis and evaluated their human relevance. Both IgG- and IgE-mediated anaphylaxis were characterized by decreased basophil and monocyte percentages and an increased neutrophil percentage in mouse blood. IgE- but not IgG-mediated murine anaphylaxis was accompanied by large increases in IL-4 secretion, plasma soluble IL-4 receptor-α (IL-4Rα) concentration, and T-cell membrane IL-4Rα expression. T-cell IL-4Rα expression also increased when mice that express human Fcε receptor Iα were sensitized with IgG-depleted serum from a peanut-allergic individual and challenged with peanut extract. Increased T-cell IL-4Rα expression is likely to also be a marker for human IgE-mediated anaphylaxis, because IgE-activated human basophils secrete IL-4, and IL-4 increases human T-cell IL-4Rα expression in vitro. Murine IgG- but not IgE-mediated anaphylaxis was characterized by decreased neutrophil Fcγ receptor III (FcγRIII) expression that was observed even when the antigen dose was insufficient to induce shock. Human neutrophils cultured with IgG immune complexes also lost FcγRIII. These observations suggest that decreased blood neutrophil FcγRIII expression without increased IL-4Rα expression can be used to determine whether and when IgG-mediated anaphylaxis occurs in man.
IgG 介导的过敏反应发生在小鼠中，可能导致人类对输注药物的反应。为了区分 IgE 介导的和可能的 IgG 介导的人类过敏反应，我们开发了用于小鼠过敏反应的血液标志物，并评估了它们与人类的相关性。IgE 和 IgG 介导的过敏反应均表现为小鼠血液中嗜碱性粒细胞和单核细胞百分比降低，中性粒细胞百分比增加。IgE 介导的但不是 IgG 介导的小鼠过敏反应伴随着 IL-4 分泌、血浆可溶性 IL-4 受体-α（IL-4Rα）浓度和 T 细胞膜 IL-4Rα 表达的大幅增加。当用来自花生过敏个体的 IgG 耗尽的血清致敏表达人 Fcε受体 Iα 的小鼠并用花生提取物进行挑战时，T 细胞 IL-4Rα 表达也会增加。增加的 T 细胞 IL-4Rα 表达也可能是人类 IgE 介导的过敏反应的标志物，因为 IgE 激活的人嗜碱性粒细胞分泌 IL-4，IL-4 增加体外人类 T 细胞 IL-4Rα 表达。与 IgE 介导的过敏反应不同，IgG 介导的过敏反应的特征是中性粒细胞 Fcγ 受体 III（FcγRIII）表达降低，即使抗原剂量不足以引起休克也是如此。与 IgG 免疫复合物培养的人类中性粒细胞也失去了 FcγRIII。这些观察结果表明，即使没有增加的 IL-4Rα 表达，血液中性粒细胞 FcγRIII 表达的降低也可用于确定 IgG 介导的过敏反应是否以及何时发生在人类中。
