Food allergy presents a significant global health concern with up to 10% of the population affected in developed nations and a steadily increasing prevalence. In many cases, particularly with peanut, tree nut and shellfish, food allergy is a lifelong and potentially life-threatening diagnosis. While no "cure" for IgE-mediated food allergy exists, oral immunotherapy (OIT) is a promising treatment modality with the peanut OIT drug Palforzia (Aimmune Therapeutics) the only treatment for food allergy that is currently approved by the United States Food and Drug Administration. OIT primarily induces a state of desensitization with only a minority of subjects achieving sustained unresponsiveness, a state of limited clinical remission that appears to be immunologically distinct from natural tolerance. Early humoral changes during OIT include an initial increase in allergen-specific IgE, which eventually decreases to below baseline levels as OIT progresses, and a gradual increase in allergen-specific IgA and IgG4 that continues throughout the course of OIT. Basophil hyporesponsiveness and decreased skin prick test wheal size are observed within the first year of OIT, and persistence after completion of therapy has been associated with sustained unresponsiveness. In the T-cell compartment, there is an initial expansion followed by a decline in the number and activity of T helper 2 (TH 2) cells, the latter of which may be dependent on an expansion of IL-10 producing cells, including regulatory T-cells. Our understanding of the immunomodulatory effects of OIT continues to evolve, with new technologies such as single-cell transcriptional profiling and antibody epitope analysis allowing for more detailed study of T-cell and B-cell responses to OIT. In this review, we present evidence to illustrate what is currently known about the immunologic changes induced by OIT, explore potential mechanisms, and emphasize knowledge gaps where future research is needed.

中文翻译：

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口服免疫疗法的机制

食物过敏是一个重大的全球健康问题，发达国家多达 10% 的人口受到影响，并且患病率稳步上升。在许多情况下，尤其是花生、树坚果和贝类，食物过敏是一种终生且可能危及生命的诊断。虽然 IgE 介导的食物过敏没有“治愈方法”，但口服免疫疗法 (OIT) 是一种很有前途的治疗方式，花生 OIT 药物 Palforzia (Aimmune Therapeutics) 是目前美国食品药品监督管理局批准的唯一食物过敏治疗方法行政。OIT 主要诱导一种脱敏状态，只有少数受试者实现持续无反应，这是一种在免疫学上与自然耐受不同的有限临床缓解状态。OIT 期间的早期体液变化包括过敏原特异性 IgE 的初始增加，随着 OIT 的进展最终降至基线水平以下，以及过敏原特异性 IgA 和 IgG4 的逐渐增加，并在整个 OIT 过程中持续。在 OIT 的第一年内观察到嗜碱性粒细胞低反应性和皮肤点刺试验风团大小减小，并且完成治疗后的持续性与持续无反应性有关。在 T 细胞区室中，T 辅助细胞 2 (TH 2) 的数量和活性会随着初始扩增而下降，后者可能依赖于产生 IL-10 的细胞的扩增，包括调节T细胞。我们对 OIT 的免疫调节作用的理解不断发展，采用单细胞转录谱和抗体表位分析等新技术，可以更详细地研究 T 细胞和 B 细胞对 OIT 的反应。在这篇综述中，我们提供了证据来说明目前对 OIT 引起的免疫变化的了解，探索潜在的机制，并强调需要未来研究的知识差距。