f420 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 (1). Peach showed the second-highest prevalence (7.9%) of IgE sensitization to foods after hazelnut (9.3%) in another European multi-country survey (2).

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 (3).

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 (4).

Environmental Characteristics

Source and tissue

Pru p 3 is an important allergen present in peach, which is a nsLTP1weighing 9 kDa (5). Peach pericarp (outer surface of fruits) is known to have high concentration of LTPs (6). The peach skin holds around 7 times higher concentration of LTP per mg of freeze-dried material than the pulp. Peach peel contains higher protein and LTP content than the pulp (5). Peach fuzz is also rich in Pru p 3 (7).

Botton et al. (2002) identified that the nsLTPs in peach are expressed as two isoforms: LTP 1, usually found in pollinated flowers and LTP 2 in the ovary. They could detect only LTP mRNA in the fruit (8, 9).

A study reported of Pru p 3 presence in peach leaves as an inhalant allergen source in 37 peach crop workers suffering from recurrent work-related asthma and rhino-conjunctivitis. (10).

Recombinant allergen (rPru p 3) can be produced through a yeast strain carrying a cloned cDNA encoding Prunus persica allergen Pru p 3 (11).

Clinical Relevance

Cross-reactive Molecules

LTPs are one of the important allergens found common in Rosaceae fruit family, various vegetables, and nuts (15). nsLTPs are referred as plant panallergens (pan means ‘all’ in Greek) (16) due to its widespread distribution among plant-foods and pollens (17). 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 (17).

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. (4).

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 (18).

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) (12) .

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 (9, 13).

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) (5).

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 (14). 

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 (19).

Molecular Aspects

Biochemistry

The structure of nsLTP (like Pru p 3 in peach) contains an alpha-helical compact domain with its four helices joined by short loops. Its amino acid sequence consists of eight cysteine residues making a network of four disulfide bridges (20). This structure makes the Pru p 3 molecule heat-stable and resistant to pH variations (21) .

The LTP protein framework forms a hydrophobic tunnel which helps in non-specific binding of fatty acids and phospholipids (6). One of the primary functions of LTP is to transfer lipids intracellularly. Other functions include, stabilizing the cell membrane and cuticle, and defending against phytopathogens (6, 20).

The N-terminal signal peptide can allow the secretion of LTP to the extracellular component providing for the extracellular assembly (6).

Isoforms, epitopes, antibodies

Isoallergens of Pru p 3

A study by Garcia-Casado et al. (2003) identified three sequence regions in Pru p 3 (11-25, 31-45, and 71-80), as its main IgE binding regions. Substitution with the triple mutant R39/ T40/R44 (positions 31-45) in rPru p 3 decreased the IgE binding to Pru p 3 by about 5 times (24).

In a study using a pool of sera from peach-allergic individuals, both the recombinant and natural forms of Pru p 3 exhibited similar IgE binding properties (25).

Cavatorta et al. (2010) used an in-vitro model to determine the gastric digestion of Pru p 3. The study found Pru p 3 to be resistant to pepsin for a longer duration. This study also compared Pru p 3 allergenicity in-vivo, using serum from one allergic and one non-allergenic patient. IgE reactivity to Pru p 3 and some high molecular weight (HMW) peptides in the sera of the allergic patient was observed. It was implied that even after Pru p 3 is digested, the Pru p 3 core remains linked to the disulfide bridges that can cause an allergic reaction (26).

Cross-reactivity

LTP from peach acts as a standard pan-allergen of the LTP family (26).

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) (20).

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. (4).

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%). (18).

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 (13). 

Diagnostic Relevance

Disease Severity

Pru p 3 is one of the diagnostic markers for Rosaceae-related allergies (6) [p65]. In Southern Europe, Pru p 3 is associated with severe systemic symptoms and OAS reactions (27).

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 (11).

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) (14).

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 (28).

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) (29). 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 (29).

Exposure

The main exposure route for this allergen is through ingestion (22).

Compiled By

Author: Turacoz Healthcare Solutions

Reviewer: Dr. Christian Fischer

Last reviewed: January 2021