Department of Immunology, University Clinic of Rheumatology and Immunology, Inselspital, University of Bern, Bern, Switzerland.
Department of BioMedical Research, University of Bern, Bern, Switzerland.
Front Immunol. 2022 Oct 6;13:892631. doi: 10.3389/fimmu.2022.892631. eCollection 2022.
Successful treatment of IgE mediated allergies by allergen-specific immunotherapy (AIT) usually correlates with the induction of allergen-specific IgG4. However, it is not clear whether IgG4 prevents the allergic reaction more efficiently than other IgG subclasses. Here we aimed to compare allergen-specific monoclonal IgG1 and IgG4 antibodies in their capacity to inhibit type I allergic reactions by engaging FcγRIIb. We found that IgG1, which is the dominant subclass induced by viruses, binds with a similar affinity to the FcγRIIb as IgG4 and is comparable at blocking human basophil activation from allergic patients; both by neutralizing the allergen as well as engaging the inhibitory receptor FcγRIIb. Hence, the IgG subclass plays a limited role for the protective efficacy of AIT even if IgG4 is considered the best correlate of protection, most likely simply because it is the dominant subclass induced by classical AITs.
通过过敏原特异性免疫疗法（AIT）成功治疗 IgE 介导的过敏反应通常与诱导过敏原特异性 IgG4 相关。然而，目前尚不清楚 IgG4 是否比其他 IgG 亚类更有效地预防过敏反应。在这里，我们旨在通过结合 FcγRIIb 比较过敏原特异性单克隆 IgG1 和 IgG4 抗体在抑制 I 型过敏反应方面的能力。我们发现，作为病毒诱导的主要亚类的 IgG1 与 IgG4 以相似的亲和力结合到 FcγRIIb 上，并且在阻断来自过敏患者的人嗜碱性粒细胞活化方面具有可比性；既能中和过敏原，又能结合抑制性受体 FcγRIIb。因此，即使 IgG4 被认为是最佳保护相关性，IgG 亚类在 AIT 的保护效果中也只起有限的作用，这很可能仅仅是因为它是经典 AIT 诱导的主要亚类。
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