Background

Three years of treatment with either sublingual or subcutaneous allergen immunotherapy has been shown to be effective and to induce long-term tolerance. The Gauging Response in Allergic Rhinitis to Sublingual and Subcutaneous Immunotherapy (GRASS) trial demonstrated that 2 years of treatment through either route was effective in suppressing the response to nasal allergen challenge, although it was insufficient for inhibition 1 year after discontinuation.

Objective

We sought to examine in the GRASS trial the time course of immunologic changes during 2 years of sublingual and subcutaneous immunotherapy and for 1 year after treatment discontinuation.

Methods

We performed multimodal immunomonitoring to assess allergen-specific CD4 T-cell properties in parallel with analysis of local mucosal cytokine responses induced by nasal allergen exposure and humoral immune responses that included IgE-dependent basophil activation and measurement of serum inhibitory activity for allergen-IgE binding to B cells (IgE-facilitated allergen binding).

Results

All 3 of these distinct arms of the immune response displayed significant and coordinate alterations during 2 years of allergen desensitization, followed by reversal at 3 years, reflecting a lack of a durable immunologic effect. Although frequencies of antigen-specific T_H2 cells in peripheral blood determined by using HLA class II tetramer analysis most closely paralleled clinical outcomes, IgE antibody–dependent functional assays remained inhibited in part 1 year after discontinuation.

Conclusion

Two years of allergen immunotherapy were effective but insufficient for long-term tolerance. Allergen-specific T_H2 cells most closely paralleled the transient clinical outcome, and it is likely that recurrence of the T-cell drivers of allergic immunity abrogated the potential for durable tolerance. On the other hand, the persistence of IgE blocking antibody 1 year after discontinuation might be an early indicator of a protolerogenic mechanism.

中文翻译：

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同步免疫改变反映了过敏原免疫治疗期间的临床反应

背景

三年的舌下或皮下过敏原免疫治疗已被证明是有效的，并能诱导长期耐受。变应性鼻炎对舌下和皮下免疫治疗 (GRASS) 试验的反应衡量表明，通过任一途径进行 2 年的治疗可有效抑制对鼻腔过敏原挑战的反应，尽管在停药后 1 年仍不足以抑制。

客观的

我们试图在 GRASS 试验中检查舌下和皮下免疫治疗 2 年期间以及治疗停止后 1 年期间免疫学变化的时间进程。

方法

我们进行了多模式免疫监测以评估过敏原特异性 CD4 T 细胞特性，同时分析了鼻过敏原暴露引起的局部粘膜细胞因子反应和体液免疫反应，包括 IgE 依赖性嗜碱性粒细胞激活和测量过敏原-IgE 结合的血清抑制活性B 细胞（IgE 促进过敏原结合）。

结果

在 2 年的过敏原脱敏过程中，所有这 3 个不同的免疫反应臂都显示出显着和协调的变化，随后在 3 年时逆转，反映出缺乏持久的免疫作用。尽管通过使用 HLA II 类四聚体分析确定的外周血中抗原特异性 T _{H 2 细胞的频率与临床结果最接近平行，但 IgE 抗体依赖性功能测定在停药后 1 年内仍然受到抑制。}

结论

两年的过敏原免疫治疗有效但不足以达到长期耐受。过敏原特异性 T _H 2 细胞最接近短暂的临床结果，很可能是过敏性免疫的 T 细胞驱动因素的复发消除了持久耐受的可能性。另一方面，停药后 1 年 IgE 阻断抗体的持续存在可能是促耐受机制的早期指标。