Peanuts and tree nuts are two of the most common elicitors of immunoglobulin E (IgE)-mediated food allergy. Nut allergy is frequently associated with systemic reactions and can lead to potentially life-threatening respiratory and circulatory symptoms. Furthermore, nut allergy usually persists throughout life. Whether sensitized patients exhibit severe and life-threatening reactions (e.g., anaphylaxis), mild and/or local reactions (e.g., pollen-food allergy syndrome) or no relevant symptoms depends much on IgE recognition of digestion-resistant class I food allergens, IgE cross-reactivity of class II food allergens with respiratory allergens and clinically not relevant plant-derived carbohydrate epitopes, respectively. Accordingly, molecular allergy diagnosis based on the measurement of allergen-specific IgE levels to allergen molecules provides important information in addition to provocation testing in the diagnosis of food allergy. Molecular allergy diagnosis helps identifying the genuinely sensitizing nuts, it determines IgE sensitization to class I and II food allergen molecules and hence provides a basis for personalized forms of treatment such as precise prescription of diet and allergen-specific immunotherapy (AIT). Currently available forms of nut-specific AIT are based only on allergen extracts, have been mainly developed for peanut but not for other nuts and, unlike AIT for respiratory allergies which utilize often subcutaneous administration, are given preferentially by the oral route. Here we review prevalence of allergy to peanut and tree nuts in different populations of the world, summarize knowledge regarding the involved nut allergen molecules and current AIT approaches for nut allergy. We argue that nut-specific AIT may benefit from molecular subcutaneous AIT (SCIT) approaches but identify also possible hurdles for such an approach and explain why molecular SCIT may be a hard nut to crack.

花生和坚果是免疫球蛋白 E (IgE) 介导的食物过敏最常见的两种诱发因素。坚果过敏通常与全身反应有关，并可能导致潜在危及生命的呼吸和循环系统症状。此外，坚果过敏通常会持续一生。致敏患者是否表现出严重和危及生命的反应（例如过敏反应）、轻微和/或局部反应（例如花粉食物过敏综合征）或没有相关症状，很大程度上取决于 IgE 对难消化的 I 类食物过敏原的识别，IgE II类食物过敏原分别与呼吸道过敏原和临床上不相关的植物源碳水化合物表位的交叉反应性。因此，基于对过敏原分子的过敏原特异性IgE水平的测量的分子过敏诊断除了在食物过敏的诊断中进行激发试验之外还提供了重要的信息。分子过敏诊断有助于识别真正致敏的坚果，确定 IgE 对 I 类和 II 类食物过敏原分子的敏感性，从而为个性化治疗形式（例如精确饮食处方和过敏原特异性免疫疗法 (AIT)）提供基础。目前可用的坚果特异性 AIT 形式仅基于过敏原提取物，主要针对花生开发，而不是针对其他坚果，并且与通常采用皮下给药的呼吸道过敏 AIT 不同，优先通过口服途径给药。在此，我们回顾了世界不同人群对花生和木本坚果过敏的流行情况，总结了有关坚果过敏原分子的知识以及当前针对坚果过敏的 AIT 方法。我们认为，坚果特异性 AIT 可能会受益于分子皮下 AIT (SCIT) 方法，但也确定了这种方法可能存在的障碍，并解释了为什么分子 SCIT 可能是一个难以破解的难题。