Tamaș Tudor Paul, Ciurariu Elena
Discipline of Immunology and Allergology, Biology, Department of Functional Sciences III, "Victor Babeș" University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, 300041 Timişoara, Romania.
Discipline of Physiology, Department of Functional Sciences III, "Victor Babeș" University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, 300041 Timişoara, Romania.
Int J Mol Sci. 2025 Apr 9;26(8):3535. doi: 10.3390/ijms26083535.
Allergen immunotherapy (AIT) is a well-established treatment aimed at reducing allergen sensitivity by gradually exposing the immune system to increasing doses of allergens. This promotes desensitization and immune tolerance through multiple mechanisms. AIT offers long-term immune modulation and is considered a potentially curative certain forms of allergic diseases. Altered antibody responses is a key mechanism of AIT in the production of allergen-specific IgG4 antibodies, which act as blocking antibodies to prevent allergen binding to IgE on mast cells (MCs) and basophils. However, IgG4 responses are sometimes ineffective due to variations in antibody affinity and epitope targeting. Reverse class switching from IgE to IgG4 and selective depletion of IgE-producing B cells represent potential strategies to improve AIT efficacy. Tregs play a central role in AIT by suppressing Th2-driven allergic responses and promoting immune tolerance through anti-inflammatory cytokines interleukin (IL)-10 and transforming growth factor (TGF)-β. However, genetic and environmental factors may impair Treg function, leading to AIT failure. AIT reduces MC and basophil activation, leading to long-term suppression of allergic inflammation. It modulates IgE-FcεRI interactions and cytokine signaling pathways, but in some cases, anaphylactic reactions or resistance to MC desensitization may occur. Discussion and conclusions: While AIT is a highly effective allergy treatment, variability in immune responses can impact its success. Advances in biologic therapies offer potential synergies with AIT. Understanding these interactions will help refine AIT strategies and improve patient outcomes.
变应原免疫疗法（AIT）是一种成熟的治疗方法，旨在通过逐渐让免疫系统接触递增剂量的变应原，来降低变应原敏感性。这通过多种机制促进脱敏和免疫耐受。AIT可提供长期的免疫调节，被认为对某些形式的过敏性疾病具有潜在的治愈作用。抗体反应的改变是AIT产生变应原特异性IgG4抗体的关键机制，这些抗体作为阻断性抗体，可防止变应原与肥大细胞（MCs）和嗜碱性粒细胞上的IgE结合。然而，由于抗体亲和力和表位靶向性的差异，IgG4反应有时会无效。从IgE向IgG4的反向类别转换以及产生IgE的B细胞的选择性耗竭，是提高AIT疗效的潜在策略。调节性T细胞（Tregs）在AIT中发挥核心作用，通过抑制Th2驱动的过敏反应，并通过抗炎细胞因子白细胞介素（IL）-10和转化生长因子（TGF）-β促进免疫耐受。然而，遗传和环境因素可能会损害Treg功能，导致AIT失败。AIT可减少MC和嗜碱性粒细胞的激活，从而长期抑制过敏性炎症。它可调节IgE-FcεRI相互作用和细胞因子信号通路，但在某些情况下，可能会发生过敏反应或对MC脱敏产生抗性。讨论与结论：虽然AIT是一种高效的过敏治疗方法，但免疫反应的变异性会影响其治疗效果。生物疗法的进展为AIT提供了潜在的协同作用。了解这些相互作用将有助于优化AIT策略并改善患者预后。
