The anti-IgE mAb omalizumab induces adverse reactions by engaging Fcγ receptors
The anti-IgE mAb omalizumab induces adverse reactions by engaging Fcγ receptors
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DOI：
10.1172/jci129697
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发表时间：
2020-03-02
影响因子：
15.9
通讯作者：
Reber, Laurent L.
中科院分区：
文献类型：
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作者：
Balbino, Bianca;Herviou, Pauline;Reber, Laurent L.
Omalizumab是一种抗ige单克隆抗体（mAb），被批准用于治疗严重哮喘和慢性自发性荨麻疹。使用omalizumab与报道的副作用有关，从注射部位的局部皮肤炎症到全身过敏反应。迄今为止，omalizumab诱导不良反应的机制尚不清楚。在这里，我们证明了omalizumab和IgE之间形成的免疫复合物可以通过参与Fc γ r人源化小鼠的IgG受体（Fc γ Rs）诱导皮肤炎症和过敏反应。我们进一步开发了一种fc工程突变版本的omalizumab，并证明该单抗在阻断ige介导的过敏反应方面与omalizumab同样有效，但不会诱导F γ 7r依赖性不良反应。总体而言，我们的数据表明omalizumab可以通过参与Fc γ Rs诱导皮肤炎症和过敏反应，并证明Fc工程版本的mAb可用于减少此类不良反应。
Omalizumab is an anti-IgE monoclonal antibody (mAb) approved for the treatment of severe asthma and chronic spontaneous urticaria. Use of omalizumab is associated with reported side effects ranging from local skin inflammation at the injection site to systemic anaphylaxis. To date, the mechanisms through which omalizumab induces adverse reactions are still unknown. Here, we demonstrated that immune complexes formed between omalizumab and IgE can induce both skin inflammation and anaphylaxis through engagement of IgG receptors (Fc gamma Rs) in Fc gamma R-humanized mice. We further developed an Fc-engineered mutant version of omalizumab, and demonstrated that this mAb is equally potent as omalizumab at blocking IgE-mediated allergic reactions, but does not induce F gamma 7R-dependent adverse reactions. Overall, our data indicate that omalizumab can induce skin inflammation and anaphylaxis by engaging Fc gamma Rs, and demonstrate that Fc-engineered versions of the mAb could be used to reduce such adverse reactions.