过敏的病因与2型炎症反应密切相关,最终导致过敏原特异性免疫球蛋白E(IgE)的产生。许多过敏状况的关键驱动因素。在高层次上,初始过敏原暴露会破坏上皮完整性,通过包括IL-25、IL-33和TSLP的警示素引发局部炎症,激活2型先天淋巴细胞以及其他免疫细胞分泌2型细胞因子IL-4,IL-5和IL-13,促进Th2细胞发育和嗜酸性粒细胞募集。Th2细胞依赖性B细胞活化促进过敏原特异性IgE的产生,与嗜碱性粒细胞和肥大细胞稳定结合。这些细胞在过敏原再暴露时的快速脱粒导致过敏症状。我们对过敏性病理生理学的分子和细胞机制的理解的最新进展显着影响了治疗干预策略的发展。在这次审查中,我们强调了过敏级联中的关键治疗目标,特别关注过去,使用单克隆抗体的当前和未来的治疗方法。特定靶向警报,2型细胞因子和IgE在包括哮喘在内的不同过敏适应症中显示出不同程度的临床益处,慢性自发性荨麻疹,特应性皮炎,慢性鼻-鼻窦炎伴鼻息肉,食物过敏和嗜酸性食管炎。虽然多种治疗性抗体已被批准用于临床,科学家们仍在努力改善目前的治疗方法。这里,我们提供背景来理解治疗靶向策略及其局限性,讨论知识差距和有希望的未来方向,以提高过敏性疾病管理的临床疗效。
The etiology of allergy is closely linked to type 2 inflammatory responses ultimately leading to the production of allergen-specific immunoglobulin E (IgE), a key driver of many allergic conditions. At a high level, initial allergen exposure disrupts epithelial integrity, triggering local inflammation via alarmins including IL-25, IL-33, and TSLP, which activate type 2 innate lymphoid cells as well as other immune cells to secrete type 2 cytokines IL-4, IL-5 and IL-13, promoting Th2 cell development and eosinophil recruitment. Th2 cell dependent B cell activation promotes the production of allergen-specific IgE, which stably binds to basophils and mast cells. Rapid degranulation of these cells upon allergen re-exposure leads to allergic symptoms. Recent advances in our understanding of the molecular and cellular mechanisms underlying allergic pathophysiology have significantly shaped the development of therapeutic intervention strategies. In this review, we highlight key therapeutic targets within the allergic cascade with a particular focus on past, current and future treatment approaches using monoclonal antibodies. Specific targeting of alarmins, type 2 cytokines and IgE has shown varying degrees of clinical benefit in different allergic indications including asthma, chronic spontaneous urticaria, atopic dermatitis, chronic rhinosinusitis with nasal polyps, food allergies and eosinophilic esophagitis. While multiple therapeutic antibodies have been approved for clinical use, scientists are still working on ways to improve on current treatment approaches. Here, we provide context to understand therapeutic targeting strategies and their limitations, discussing both knowledge gaps and promising future directions to enhancing clinical efficacy in allergic disease management.