Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology (POSTECH), Pohang, Gyeongbuk, Republic of Korea.
Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyeongbuk, Republic of Korea.
Nat Commun. 2022 Sep 27;13(1):5669. doi: 10.1038/s41467-022-33176-1.
IgE is central to the development of allergic diseases, and its neutralization alleviates allergic symptoms. However, most of these antibodies are based on IgG1, which is associated with an increased risk of fragment crystallizable-mediated side effects. Moreover, omalizumab, an anti-IgE antibody approved for therapeutic use, has limited benefits for patients with high IgE levels. Here, we assess a fusion protein with extracellular domain of high affinity IgE receptor, FcεRIα, linked to a IgD/IgG4 hybrid Fc domain we term IgE to reduce the risk of IgG1 Fc-mediated side effects. IgE shows enhanced IgE binding affinity compared to omalizumab. We also see an enhanced therapeutic effect of IgE in food allergy models when combined with Bifidobacterium longum, which results in mast cell number and free IgE levels. The combination of IgE and B. longum may therefore represent a potent treatment for allergic patients with high IgE levels.
IgE 是过敏疾病发展的核心，其中和可缓解过敏症状。然而，这些抗体大多基于 IgG1，这与片段结晶化介导的副作用风险增加有关。此外，奥马珠单抗是一种已批准用于治疗的抗 IgE 抗体，对高 IgE 水平的患者益处有限。在这里，我们评估了一种融合蛋白，该蛋白将高亲和力 IgE 受体的细胞外结构域与 IgD/IgG4 杂合 Fc 结构域连接起来，我们将其称为 IgE，以降低 IgG1 Fc 介导的副作用风险。IgE 与奥马珠单抗相比，表现出增强的 IgE 结合亲和力。当与长双歧杆菌结合时，我们还观察到 IgE 在食物过敏模型中的治疗效果增强，从而导致肥大细胞数量和游离 IgE 水平降低。因此，IgE 与长双歧杆菌的组合可能代表了一种治疗高 IgE 水平过敏患者的有效方法。
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