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. 2021 May 18;11(3):e12010.
doi: 10.1002/clt2.12010. eCollection 2021 May.

Non-specific lipid-transfer proteins: Allergen structure and function, cross-reactivity, sensitization, and epidemiology

Isabel J Skypala  1 , Ricardo Asero  2 , Domingo Barber  3   4 , Lorenzo Cecchi  5 , Arazeli Diaz Perales  6 , Karin Hoffmann-Sommergruber  7 , Elide A Pastorello  8 , Ines Swoboda  9 , Joan Bartra  10 , Didier G Ebo  11 , Margaretha A Faber  11 , Montserrat Fernández-Rivas  12 , Francesca Gomez  13 , Anastasios P Konstantinopoulos  14 , Olga Luengo  15 , Ronald van Ree  16 , Enrico Scala  17 , Stephen J Till  18   19 ; European Academy of Allergy; Clinical Immunology (EAACI) Task Force: Non‐specific Lipid Transfer Protein Allergy Across Europe
Affiliations

Non-specific lipid-transfer proteins: Allergen structure and function, cross-reactivity, sensitization, and epidemiology

Isabel J Skypala et al. Clin Transl Allergy. .

Abstract

Background: 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.

Aim: 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.

Materials and methods: 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".

Results: 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.

Discussion: 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.

Conclusion: 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.

Keywords: LTP; allergy; epidemiology; food; lipid transfer protein; sensitization.

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Conflict of interest statement

The following authors declare that they have competing interests: K. Hoffmann‐Somergruber has received support from the Austrian Science funds (FWF) by SFB Subproject F‐4603, L. Cecchi has received honoraria from Malseci, Menarini, Mylan and Thermofisher, D Barber is a scientific advisor to ALK and AIMMUNE, E.Scala has received consultant arrangements and speakers’ bureau participation from Stallergenes and Thermo Fisher Scientific. M. Fernández‐Rivas declares grants from Spanish Government (ISCIII; MINECO), Aimmune Therapeutics and Diater to her organization; consultancy fees from Aimmune, DBV, Novartis, SPRIM; lecture fees from Aimmune, ALK, Diater, GSK, HAL Allergy, Thermofisher Scientific, outside the submitted work. R. van Ree undertakes consultancies for HAL Allergy BV, Citeq BV and Angany Inc, has received honoraria from HAL Allergy BV, ThermoFisher Scientific and funding support from the European Commission, Dutch Science Foundation, Health Holland. I. Skypala, D. Ebo, M. Faber, A Diaz‐Perales, I Swoboda, F Gomez, R. Asero, E. Pastorello, O. Luengo, S Till, J Bartra, A Konstantinopoulos have no conflict of interests to declare

Figures

FIGURE 1
FIGURE 1
Structure of lipid‐transfer protein allergens
FIGURE 2
FIGURE 2
Structure of Pru p 3: (A) surface model, (B) ribbon model, (C) internal cavity with ligand binding
FIGURE 3
FIGURE 3
World‐wide reported lipid‐transfer protein sensitization
See this image and copyright information in PMC

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