Phelps Allyssa, Bruton Kelly, Grydziuszko Emily, Koenig Joshua F E, Jordana Manel
Department of Medicine, McMaster Immunology Research Centre (MIRC), Schroeder Allergy and Immunology Research Institute, McMaster University, Hamilton, ON, Canada.
Front Allergy. 2022 Feb 9;3:826623. doi: 10.3389/falgy.2022.826623. eCollection 2022.
A series of landmark studies have provided conclusive evidence that the early administration of food allergens dramatically prevents the emergence of food allergy. One of the greatest remaining challenges is whether patients with established food allergy can return to health. This challenge is particularly pressing in the case of allergies against peanut, tree nuts, fish, and shellfish which are lifelong in most patients and may elicit severe reactions. The standard of care for food allergy is allergen avoidance and the timely administration of epinephrine upon accidental exposure. Epinephrine, and other therapeutic options like antihistamines provide acute symptom relief but do not target the underlying pathology of the disease. In principle, any transformative treatment for established food allergy would require the restoration of a homeostatic immunological state. This may be attained through either an active, non-harmful immune response (immunological tolerance) or a lack of a harmful immune response (e.g., anergy), such that subsequent exposures to the allergen do not elicit a clinical reaction. Importantly, such a state must persist beyond the course of the treatment and exert its protective effects permanently. In this review, we will discuss the immunological mechanisms that maintain lifelong food allergies and are, consequently, those which must be dismantled or reprogrammed to instate a clinically non-reactive state. Arguably, the restoration of such a state in the context of an established food allergy would require a reprogramming of the immune response against a given food allergen. We will discuss existing and experimental therapeutic strategies to eliminate IgE reactivity and, lastly, will propose outstanding questions to pave the road to the development of novel, transformative therapeutics in food allergy.
一系列具有里程碑意义的研究提供了确凿证据，表明早期给予食物过敏原能显著预防食物过敏的出现。目前最大的挑战之一是，已确诊食物过敏的患者能否恢复健康。对于花生、坚果、鱼类和贝类过敏的情况，这一挑战尤为紧迫，因为在大多数患者中，这些过敏是终身性的，且可能引发严重反应。食物过敏的标准治疗方法是避免接触过敏原，并在意外接触后及时注射肾上腺素。肾上腺素以及其他治疗选择（如抗组胺药）可缓解急性症状，但无法针对该疾病的潜在病理机制。原则上，任何针对已确诊食物过敏的变革性治疗都需要恢复免疫稳态。这可以通过主动的、无害的免疫反应（免疫耐受）或缺乏有害免疫反应（例如无反应性）来实现，从而使后续接触过敏原时不会引发临床反应。重要的是，这种状态必须在治疗过程结束后持续存在，并永久发挥保护作用。在本综述中，我们将讨论维持终身食物过敏的免疫机制，因此也就是那些必须被消除或重新编程以建立临床无反应状态的机制。可以说，在已确诊食物过敏的情况下恢复这种状态需要对针对特定食物过敏原的免疫反应进行重新编程。我们将讨论现有的和实验性的消除IgE反应性的治疗策略，最后提出一些突出问题，为开发治疗食物过敏的新型变革性疗法铺平道路。
