Background

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.

Objective

We compared the quantity, quality, and IgE-blocking bioactivity of SLIT-induced Mal d 1-specific IgG antibodies in both treatment groups.

Methods

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.

Results

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.

Conclusion

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.

中文翻译：

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SLIT后与重组Mal d 1结合的IgE阻断抗体与改善的苹果过敏症相吻合。

背景

我们最近报道说，重组（r）Mal d 1而不是rBet v 1的16周舌下免疫治疗（SLIT）显着改善了与桦树花粉相关的苹果过敏。变应原特异性IgE阻断IgG抗体已与临床疗效相关联。

目的

我们比较了两个治疗组中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。

方法

在ELISA中评估SLIT前后的rMal d 1特异性IgG抗体，以及抑制未经过敏处理的桦木花粉相关苹果过敏者嗜碱性粒细胞上苹果变应原诱导的CD63上调的能力。比较耗尽了IgG1或IgG4的SLIT后血清的IgE阻断活性。在ELISA中，与rMal d 1结合的IgG1与rMal d 1和rBet v 1竞争。

结果

具有rMal d 1和rBet v 1的SLIT诱导了可比较水平的rMal d 1特异性IgG1，IgG2，IgG3和IgG4抗体。只有rMal d 1 SLIT血清显示IgE阻断活性，但由于IgG1的消耗而显着降低，而IgG4的消耗则较小。在竞争性ELISA中，rMal d 1完全抑制了rMal d 1 SLIT血清中与Mal d 1结合的IgG1，而rBet v 1则未完全抑制。相应地，Bet v 1是IgG1与Mald 1结合的更强竞争者。投注后v 1 SLIT血清。

结论

rMal d 1 SLIT持续16周诱导功能性的，主要是Mal d 1特异性IgE阻断抗体，而rBet v 1 SLIT诱导的Bet v 1特异性，Mal d 1交叉反应性IgG抗体具有有限的交叉阻断活性。这些结果为桦木花粉免疫疗法在桦木花粉相关食品过敏中疗效有限提供了可能的解释，并表明功能性IgE阻断IgG1抗体在过敏治疗的早期阶段起着主要的保护作用。