Skypala Isabel J, Asero Ricardo, Barber Domingo, Cecchi Lorenzo, Diaz Perales Arazeli, Hoffmann-Sommergruber Karin, Pastorello Elide A, Swoboda Ines, Bartra Joan, Ebo Didier G, Faber Margaretha A, Fernández-Rivas Montserrat, Gomez Francesca, Konstantinopoulos Anastasios P, Luengo Olga, van Ree Ronald, Scala Enrico, Till Stephen J
Department of Allergy & Clinical Immunology Royal Brompton & Harefield NHS Foundation Trust Imperial College London UK.
Ambulatorio di Allergologia Clinica San Carlo Milan Italy.
Clin Transl Allergy. 2021 May 18;11(3):e12010. doi: 10.1002/clt2.12010. eCollection 2021 May.
Discovered and described 40 years ago, non-specific lipid transfer proteins (nsLTP) are present in many plant species and play an important role protecting plants from stressors such as heat or drought. In the last 20 years, sensitization to nsLTP and consequent reactions to plant foods has become an increasing concern.
The aim of this paper is to review the evidence for the structure and function of nsLTP allergens, and cross-reactivity, sensitization, and epidemiology of nsLTP allergy.
A Task Force, supported by the European Academy of Allergy & Clinical Immunology (EAACI), reviewed current evidence and provide a signpost for future research. The search terms for this paper were "Non-specific Lipid Transfer Proteins", "LTP syndrome", "Pru p 3", "plant food allergy", "pollen-food syndrome".
Most nsLTP allergens have a highly conserved structure stabilised by 4-disulphide bridges. Studies on the peach nsLTP, Pru p 3, demonstrate that nsLTPs are very cross-reactive, with the four major IgE epitopes of Pru p 3 being shared by nsLTP from other botanically related fruits. These nsLTP allergens are to varying degrees resistant to heat and digestion, and sensitization may occur through the oral, inhaled or cutaneous routes. In some populations, Pru p 3 is the primary and sole sensitizing allergen, but many are poly-sensitised both to botanically un-related nsLTP in foods, and non-food sources of nsLTP such as Cannabis sativa, Platanus acerifolia, (plane tree), Ambrosia artemisiifolia (ragweed) and Artemisia vulgaris (mugwort). Initially, nsLTP sensitization appeared to be limited to Mediterranean countries, however more recent studies suggest clinically relevant sensitization occurs in North Atlantic regions and also countries in Northern Europe, with nsLTP sensitisation profiles being broadly similar.
These robust allergens have the potential to sensitize and provoke symptoms to a large number of plant foods, including those which are raw, cooked or processed. It is unknown why some sensitized individuals develop clinical symptoms to foods whereas others do not, or indeed what other allergens besides Pru p 3 may be primary sensitising allergens. It is clear that these allergens are also relevant in non-Mediterranean populations and there needs to be more recognition of this.
Non-specific LTP allergens, present in a wide variety of plant foods and pollens, are structurally robust and so may be present in both raw and cooked foods. More studies are needed to understand routes of sensitization and the world-wide prevalence of clinical symptoms associated with sensitization to these complex allergens.
非特异性脂质转移蛋白（nsLTP）于40年前被发现并描述，存在于许多植物物种中，在保护植物免受高温或干旱等应激源影响方面发挥着重要作用。在过去20年里，对nsLTP的致敏作用以及随之而来的对植物性食物的反应已日益受到关注。
本文旨在综述nsLTP变应原的结构与功能、交叉反应性、致敏作用及nsLTP过敏的流行病学证据。
一个由欧洲变态反应与临床免疫学会（EAACI）支持的特别工作组，回顾了当前证据并为未来研究提供了指引。本文的检索词为“非特异性脂质转移蛋白”“LTP综合征”“Pru p 3”“植物性食物过敏”“花粉 - 食物综合征”。
大多数nsLTP变应原具有由4个二硫键稳定的高度保守结构。对桃nsLTP即Pru p 3的研究表明，nsLTP具有很强的交叉反应性，Pru p 3的4个主要IgE表位可被其他植物学相关果实中的nsLTP共享。这些nsLTP变应原对热和消化具有不同程度的抗性，致敏可能通过口服、吸入或皮肤途径发生。在一些人群中，Pru p 3是主要且唯一的致敏变应原，但许多人对食物中植物学上不相关的nsLTP以及nsLTP的非食物来源如大麻、悬铃木、豚草和艾蒿等呈多致敏状态。最初，nsLTP致敏似乎仅限于地中海国家，然而最近的研究表明，在北大西洋地区以及北欧国家也出现了具有临床相关性的致敏情况，nsLTP致敏谱大致相似。
这些强效变应原有可能使大量植物性食物致敏并引发症状，包括生食、熟食或加工食品。尚不清楚为何一些致敏个体对食物出现临床症状而另一些人则没有，或者除了Pru p 3之外还有哪些其他变应原可能是主要致敏变应原。显然，这些变应原在非地中海人群中也具有相关性，对此需要有更多认识。
存在于多种植物性食物和花粉中的非特异性LTP变应原结构稳定，因此可能同时存在于生食和熟食中。需要开展更多研究以了解致敏途径以及与这些复杂变应原致敏相关的临床症状在全球的患病率。
