Pru p 3
Summary
The peach allergen, Pru p 3, is a non-specific lipid transfer protein type 1 (nsLTP 1) and acts as a precursor for other nsLTP-related sensitizations. Peach LTP acts as an archetype of the LTP family due to its broad distribution among the plant species. Pru p 3 cross-reactivity occurs with most members of the Rosaceae family, such as apple, plum, cherry and apricot. It can also cross-react with members containing nsLTPs from other families such as walnut, hazelnut, peanut, asparagus, lettuce, tomato, maize, onion, and carrot. Typical clinical symptoms of Pru p 3 induced allergies include oral allergy syndrome (OAS), anaphylaxis (gastrointestinal involvement, nausea, vomiting and diarrhea), generalized or contact urticaria, and sometimes severe asthma. Pru p 3 acts as a marker allergen for severe systemic symptoms and is one of the diagnostic indicators to detect allergy to Rosaceae family fruits.
Epidemiology
Worldwide distribution
The European Community Respiratory Health Survey involving sera of 4522 individuals from 13 countries stated that sensitization to peach is quite common in Western Europe, the USA, and Australia. Peach showed the second-highest prevalence (7.9%) of IgE sensitization to foods after hazelnut (9.3%) in another European multi-country survey.
An observational controlled cohort study in the U.K. compared the sensitization pattern of LTP allergy among the U.K. and Italian patients. This study reported sensitization to Pru p 3 in 29 of 35 (83%) UK patients and 33 of 37 (89%) Italian patients with LTP allergy.
Sensitivity to Pru p 3 (nsLTPs) was 83.4% (252/302) among patients with peach allergy in a prospective study conducted in Spain. This study focused on determining the clinical and sensitization profile of peach-allergic patients, due to nsLTPs (Pru p 3) sensitization, through skin prick (SPT) and specific-IgE (sIgE) tests.
Clinical Relevance
Cross-reactive Molecules
LTPs are one of the important allergens found common in Rosaceae fruit family, various vegetables, and nuts. nsLTPs are referred as plant panallergens (pan means ‘all’ in Greek) due to its widespread distribution among plant-foods and pollens. The LTPs from different plant-foods and pollens can cross-react with each other, which may cause multiple plant-food sensitizations, and lead to LTP syndrome, in allergic patients.
Bogas et al. (2020) conducted a prospective study in 302 peach-allergic patients when exposed to several plant-foods and pollens. The study concluded that majority of patients (92.9%) with peach allergy, show multi-sensitization to LTP from peach and other plant foods, and thus, may also suffer from LTP-syndrome. Symptoms such as anaphylaxis (41.2%), urticaria (47.8%) and OAS (11.7%) were observed in mono-allergic (peach LTP) patients. Patients allergic to LTP from multiple sources (including peach) experienced a prolonged history of peach allergy and additional episodes of asthma in comparison to mono-allergic individuals.
In a double-blind, placebo-controlled food challenge study using 30 peach-allergic patients, plum sensitization was correlated to severe reactions to peach. Of 30 patients, about 64% and 36% were sensitized to plum and presented systemic and local reactions to peach respectively.
Disease severity
Pru p 3 sensitization can cause OAS that includes oropharyngeal symptoms (oral pruritus, edema, vesicles and erythema localized in the pharynx or throat cavity), anaphylaxis, systemic symptoms (gastrointestinal involvement, nausea, vomiting and diarrhea, angioedema and sometimes severe asthma).
LTP sensitization generally triggers severe systemic reactions such as generalized urticaria, angioedema, asthma, and anaphylaxis due to its resistance to proteolytic digestion and heat treatment.
Some individuals show systemic reactions after direct contact with peach peel but can tolerate the pulp as peel contains seven times higher LTP (per mg of freeze-dried material).
Pastorello et al. (2013) in their study with 141 peach-allergic patients identified that about 50% of them developed peach allergy between the age of 10-29 years. They found an association of severe peach allergy with sensitization to Pru p 3 among children under 9 years.
Diagnostics
Disease Severity
Pru p 3 is one of the diagnostic markers for Rosaceae-related allergies [p65]. In Southern Europe, Pru p 3 is associated with severe systemic symptoms and OAS reactions.
A study by Diaz-Perales et al. (2003) identified that recombinant Pru p 3 (rPru p 3) shares a similar spectrum, physicochemical function, and allergenic properties as natural Pru p 3 (nPru p 3) and can be beneficial as a diagnostic aid for peach allergy.
Another finding from the Pastorello et al. (2013) study was that the anti-rPru p 3 IgE levels are inversely proportional to the age when peach-induced severe symptoms are reported for the first time by peach-allergic adults (p<0.0005).
Due to similarity of mass between Pru p 3 and Pru p 7, it is potentially challenging to separate these components during the purification of natural extracts. It is speculated that Pru p 7 might contaminate commercially purified natural Pru p 3 skin prick test extracts. This would lead to inconsistent diagnostic results. Advances in routine testing approach can resolve this.
Cross-Reactivity
There are various allergens other than Pru p 3 (nsLTP type 1) that are present in fruits of the Rosaceae family, such as Pru p 1 (Bet v 1 family member) and Pru p 4 (profilins). Since all these allergenic components tend to cross-react, Pru p 1 and Pru p 4 can also be used for detecting Rosaceae fruit allergies.
Exposure
The main exposure route for this allergen is through ingestion.
Prevention And Therapy
Experimental trials
Eichhorn et al. (2019) evaluated Pru p 3 variants for treatment of peach allergy. In 33 of 60 sera samples from peach-allergic patients, both Pru p 3 variants - proline (PV) and cysteine (CV) reduced IgE binding activity by 97% and 73% respectively. Also, PV demonstrated antibody immune response in all the mice used in-vitro with a phosphate-based adjuvant formulation compared to a hydroxide-based formulation. The authors found PV to be hypoallergenic with a stable structure eliciting an immune response which helps it to be a promising candidate for peach allergen immunotherapy.
Cross-Reactivity
LTP from peach acts as a standard pan-allergen of the LTP family.
In a study, Pasquato et al. (2006) mentioned that cross-reactivity between Rosaceae LTPs is due to similar amino acid sequence identity of nsLTP within Rosaceae family fruits (like peach, apple, apricot, cherry). Cross-reactivity between peach and species from unrelated families occurs due to sharing of nsLTP homologous IgE-epitopes in botanically unrelated species (rice, wheat, maize, barley).
A prospective study involving 252 patients with peach allergy showed that about 93.3% (235/252) of patients developed frequent sensitivity to LTP from plant-foods other than peach. sIgE reactivity was highest with Pru p 3 followed by walnut (Jug r 3), hazelnut (Cor a 8), and peanut (Ara h 9). LTP sensitization from multiple sources was prevalent in 7.1% of patients sensitized to two nsLTPs, 7.9% to three nsLTPs and 48.5% to four nsLTPs. Patients with LTP-related allergy were more sensitized to mugwort pollen compared to other aeroallergens tested.
A double-blind, placebo-controlled food challenge study in 30 peach allergic patients revealed that 90% of the peach allergic patients developed sensitivity to other Rosaceae fruits such as plum (46.3%), almonds (43.3%) and apricot (43.3%).
Salcedo et al. (2007) commented that Pru p 3 shares amino acid sequence identity with members of unrelated species (like asparagus, lettuce, cabbage, onion, and carrot) that indicates the presence of cross-reactivity between peach and these species.
References
- Burney P, Summers C, Chinn S, Hooper R, van Ree R, Lidholm J. Prevalence and distribution of sensitization to foods in the European Community Respiratory Health Survey: a EuroPrevall analysis. Allergy. 2010;65(9):1182-8.
- Burney PG, Potts J, Kummeling I, Mills ENC, Clausen M, R. Dubakiene, et al. The prevalence and distribution of food sensitization in European adults. Allergy. 2014;69(3):365-71.
- Skypala IJ, Cecchi L, Shamji MH, Scala E, Till S. Lipid Transfer Protein allergy in the United Kingdom: Characterization and comparison with a matched Italian cohort. Allergy. 2019;74(7):1340-51.
- Bogas G, Munoz-Cano R, Mayorga C, Casas R, Bartra J, Perez N, et al. Phenotyping peach-allergic patients sensitized to LTP and analysing severity biomarkers. Allergy. 2020.
- Carnes J, Fernandez-Caldas E, Gallego MT, Ferrer A, Cuesta-Herranz J. Pru p 3 (LTP) content in peach extracts. Allergy. 2002;57(11):1071-5.
- Peterson A, Kleine-Tebbe J, S S. Stable Plant Food Allergens I: Lipid Transfer Proteins. In: T K-TJaJ, editor. Molecular Allergy Diagnostics - Innovation for a Better Patient Management: Springer; 2017. p. 57-71.
- Asero R, Mistrello G, Amato S, Roncarolo D, Martinelli A, Zaccarini M. Peach fuzz contains large amounts of lipid transfer protein: is this the cause of the high prevalence of sensitization to LTP in Mediterranean countries? Eur Ann Allergy Clin Immunol. 2006;38(4):118-21.
- Botton A, Begheldo M, Rasori A, Bonghi C, Tonutti P. Differential expression of two lipid transfer protein genes in reproductive organs of peach (Prunus persica L. Batsch). Plant Science. 2002;163(5):993-1000.
- Zamieskova L, Žiarovská J, Bilčíková J, Fialková V. Natural variability of restriction profiles in non-coding part of Prunus persica (L.) Batsch. Pru p 3 gene. Acta fytotechnica et zootechnica. 2020;23(1).
- Perez-Calderon R, Gonzalo-Garijo MA, Rodriguez-Velasco FJ, Sanchez-Vega S, Bartolome-Zavala B. Occupational respiratory allergy in peach crop workers. Allergy. 2017;72(10):1556-64.
- Diaz-Perales A, Sanz ML, Garcia-Casado G, Sanchez-Monge R, Garcia-Selles FJ, Lombardero M, et al. Recombinant Pru p 3 and natural Pru p 3, a major peach allergen, show equivalent immunologic reactivity: a new tool for the diagnosis of fruit allergy. J Allergy Clin Immunol. 2003;111(3):628-33.
- Breiteneder H, Kleine-Tebbe J. PR-10-LIKE ALLERGENS. In: Matricardi P. M. K-TJ, Hoffmann H. J., et al., editor. Molecular Allergology User's Guide. Switzerland: The European Academy of Allergy and Clinical Immunology (EAACI); 2016. p. 299-310.
- Salcedo G, Sanchez-Monge R, Barber D, Diaz-Perales A. Plant non-specific lipid transfer proteins: an interface between plant defence and human allergy. Biochim Biophys Acta. 2007;1771(6):781-91.
- Pastorello EA, Farioli L, Stafylaraki C, Mascheri A, Scibilia J, Pravettoni V, et al. Anti-rPru p 3 IgE levels are inversely related to the age at onset of peach-induced severe symptoms reported by peach-allergic adults. Int Arch Allergy Immunol. 2013;162(1):45-9.
- Egger M, Hauser M, Mari A, Ferreira F, Gadermaier G. The role of lipid transfer proteins in allergic diseases. Curr Allergy Asthma Rep. 2010;10(5):326-35.
- Hauser M, Roulias A, Ferreira F, Egger M. Panallergens and their impact on the allergic patient. Allergy Asthma Clin Immunol. 2010;6(1):1.
- Pascal M, Munoz-Cano R, Reina Z, Palacin A, Vilella R, Picado C, et al. Lipid transfer protein syndrome: clinical pattern, cofactor effect and profile of molecular sensitization to plant-foods and pollens. Clin Exp Allergy. 2012;42(10):1529-39.
- Rodrigues-Alves R, Lopez A, Pereira-Santos MC, Lopes-Silva S, Spinola-Santos A, Costa C, et al. Clinical, anamnestic and serological features of peach allergy in portugal. Int Arch Allergy Immunol. 2009;149(1):65-73.
- Eichhorn S, Horschlager A, Steiner M, Laimer J, Jensen BM, Versteeg SA, et al. Rational Design, Structure-Activity Relationship, and Immunogenicity of Hypoallergenic Pru p 3 Variants. Mol Nutr Food Res. 2019;63(18):e1900336.
- Pasquato N, Berni R, Folli C, Folloni S, Cianci M, Pantano S, et al. Crystal structure of peach Pru p 3, the prototypic member of the family of plant non-specific lipid transfer protein pan-allergens. J Mol Biol. 2006;356(3):684-94.
- Pastorello E., Barber D. NON-SPECIFIC LIPID TRANSFER PROTEINS (nsLTPs). In: Matricardi P. M. K-TJ, Hoffmann H. J., et al., editor. Molecular Allergology User's Guide. Switzerland: The European Academy of Allergy and Clinical Immunology (EAACI); 2016. p. 311-20.
- WHO/IUIS. "Pru p 3." 2019 [19-11-2020]. Available from: http://www.allergen.org/viewallergen.php?aid=558.
- Pastorello EA, Ortolani C, Baroglio C, Pravettoni V, Ispano M, Giuffrida MG, et al. Complete amino acid sequence determination of the major allergen of peach (Prunus persica) Pru p 1. Biol Chem. 1999;380(11):1315-20.
- Diaz-Perales A, Garcia-Casado G, Sanchez-Monge R, Garcia-Selles FJ, Barber D, Salcedo G. cDNA cloning and heterologous expression of the major allergens from peach and apple belonging to the lipid-transfer protein family. Clin Exp Allergy. 2002;32(1):87-92.
- Cavatorta V, Sforza S, Aquino G, Galaverna G, Dossena A, Pastorello EA, et al. In vitro gastrointestinal digestion of the major peach allergen Pru p 3, a lipid transfer protein: molecular characterization of the products and assessment of their IgE binding abilities. Mol Nutr Food Res. 2010;54(10):1452-7.
- Sastre J. Molecular diagnosis in allergy. Clin Exp Allergy. 2010;40(10):1442-60.
- Tuppo L, Alessandri C, Pomponi D, Picone D, Tamburrini M, Ferrara R, et al. Peamaclein--a new peach allergenic protein: similarities, differences and misleading features compared to Pru p 3. Clin Exp Allergy. 2013;43(1):128-40.
- Ballmer-Weber B, Hoffmann-Sommergruber K. B15. ALLERGY TO FRUITS AND VEGETABLES. In: Matricardi P. M. K-TJ, Hoffmann H. J., et al., editor. MOLECULAR ALLERGOLOGY USER'S GUIDE. Switerland: EAACI; 2016.
- Gamboa PM, Caceres O, Antepara I, Sanchez-Monge R, Ahrazem O, Salcedo G, et al. Two different profiles of peach allergy in the north of Spain. Allergy. 2007;62(4):408-14.