Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria.
Department of Dermatology, Medical University of Vienna, Vienna, Austria.
J Allergy Clin Immunol. 2020 Oct;146(4):894-900.e2. doi: 10.1016/j.jaci.2020.03.015. Epub 2020 Apr 4.
We recently reported that 16 weeks of sublingual immunotherapy (SLIT) with recombinant (r) Mal d 1, but not rBet v 1, significantly improved birch pollen-related apple allergy. Allergen-specific IgE-blocking IgG antibodies have been associated with clinical efficacy.
We compared the quantity, quality, and IgE-blocking bioactivity of SLIT-induced Mal d 1-specific IgG antibodies in both treatment groups.
Pre- and post-SLIT sera were assessed for rMal d 1-specific IgG antibodies in ELISA and for their ability to inhibit apple allergen-induced upregulation of CD63 on basophils from nontreated individuals with birch pollen-related apple allergy. Post-SLIT sera depleted of IgG1 or IgG4 were compared for their IgE-blocking activity. IgG1 binding to rMal d 1 was competed with rMal d 1 and rBet v 1 in ELISA.
SLIT with rMal d 1 and rBet v 1 induced comparable levels of rMal d 1-specific IgG1, IgG2, IgG3, and IgG4 antibodies. Only post-rMal d 1 SLIT sera displayed IgE-blocking activity, which was significantly reduced by depletion of IgG1 and less so by IgG4 depletion. In competition ELISA, IgG1 binding to Mal d 1 in post-rMal d 1 SLIT sera was fully inhibited with rMal d 1 but not with rBet v 1. Correspondingly, Bet v 1 was the more potent competitor for IgG1 binding to Mal d 1 in post-rBet v 1 SLIT sera.
rMal d 1 SLIT for 16 weeks induced functional, primarily Mal d 1-specific IgE-blocking antibodies, whereas rBet v 1 SLIT induced Bet v 1-specific, Mal d 1-cross-reactive IgG antibodies with limited cross-blocking activity. These results provide a possible explanation for the limited effectiveness of birch pollen immunotherapy in birch pollen-related food allergy and indicate a dominant protective role of functional IgE-blocking IgG1 antibodies in the early phase of allergy treatment.
我们最近报道，16 周舌下免疫治疗（SLIT）用重组（r）Mal d 1，但不是 rBet v 1，显著改善了桦树花粉相关的苹果过敏。过敏原特异性 IgE 阻断 IgG 抗体与临床疗效相关。
我们比较了两组治疗中 SLIT 诱导的 Mal d 1 特异性 IgG 抗体的数量、质量和 IgE 阻断生物活性。
在 SLIT 前后评估了 rMal d 1 特异性 IgG 抗体在 ELISA 中的水平，并评估了它们抑制桦树花粉相关苹果过敏的未治疗个体嗜碱性粒细胞上苹果过敏原诱导的 CD63 上调的能力。比较了 SLIT 后 IgG1 或 IgG4 耗尽的血清的 IgE 阻断活性。在 ELISA 中，用 rMal d 1 和 rBet v 1 竞争 IgG1 与 rMal d 1 的结合。
rMal d 1 和 rBet v 1 的 SLIT 诱导了相当水平的 rMal d 1 特异性 IgG1、IgG2、IgG3 和 IgG4 抗体。只有 rMal d 1 SLIT 后血清显示 IgE 阻断活性，该活性被 IgG1 耗尽显著降低，而 IgG4 耗尽降低较少。在竞争 ELISA 中，rMal d 1 SLIT 后血清中 IgG1 与 Mal d 1 的结合被 rMal d 1 完全抑制，但不受 rBet v 1 抑制。相应地，Bet v 1 是 rBet v 1 SLIT 后血清中 IgG1 与 Mal d 1 结合的更有效竞争物。
16 周 rMal d 1 SLIT 诱导了功能性的、主要是 Mal d 1 特异性的 IgE 阻断 IgG 抗体，而 rBet v 1 SLIT 诱导了 Bet v 1 特异性的、与 Mal d 1 交叉反应的 IgG 抗体，具有有限的交叉阻断活性。这些结果为桦树花粉免疫治疗在桦树花粉相关食物过敏中的有限疗效提供了可能的解释，并表明功能性 IgE 阻断 IgG1 抗体在过敏治疗早期阶段具有主要的保护作用。
