Pru p 7
Summary
The peach allergen Pru p 7 is a marker for severe fruit-induced allergy and may be the link between severe allergic reaction to fruits and cypress pollen allergy. Pru p 7 is a gibberlin-regulated protein (GRP) and, homologous, IgE cross-reactive proteins exists in several fruits of the Rosaceae, (e. g. Japanese apricot, pomegranate) and Rutaceae families (e. g. orange) as well as in pollens from the Cupressaceae family. Pru p 7 was first described by Tuppo et al in 2013. Testing of specific IgE to Pru p 7 may be useful in order to fill the diagnostic gap observed in peach allergic patients not sensitized to the peach allergens Pru p 1 (PR-10), Pru p 3 (LTP) and Pru p 4 (profilin), a situation that seems to be especially common in areas with high cypress pollen exposure. Typical clinical symptoms of Pru p 7 induced allergy is anaphylaxis with urticaria and swelling of the face, especially the eyelids.
Epidemiology
Pru p 7 sensitivity seems to be most common in areas with high cypress pollen exposure. In a study conducted in the southern parts of France, Klingebiel et al showed that sensitization to Pru p 7 was found in 54 % (171 of 316) of patients with suspected peach allergy and 62 % (123 of 198) of patients with diagnosed peach allergy. In the group of peach allergic and Pru p 7 sensitized patients, 54 % (66 of 123) did not show IgE sensitization to any other tested peach allergen (Pru p 1, Pru p 3 or Pru p 4).
In the same study, Pru p 7 sensitivity was found to be associated with clinical severity of peach induced allergic reactions with a higher incident and ratio in grade 3 than in grade 1 or 2 reactions. Furthermore, Pru p 7 sensitization was found to be associated with the intensity of cypress pollen exposure, based on geographical location, and with IgE-reactivity to cypress pollen. In fact, Pru p 7 was the only peach allergen associated with cypress pollen sensitization. Based on the results of the study the authors speculate that cypress pollen act as the primary sensitizer in Pru p 7 induced peach allergy and that sensitization to Pru p 7 is a characteristic of a sub-type of Cupressaceae pollen allergy causing severe peach allergy.
In a recent report, Ehrenberg et al reveal more evidence related to the connection between Cypress pollen allergy and Pru p 7 sensitivity. In their study, they show that the Cupressaceae pollen allergen involved in severe fruit allergy is a 7 kDa protein belonging to the GRP family, named Cup s 7. They also show that the IgE biding capacity was substantially higher to Cup s 7 than to Pru p 7 in sera of 54 peach allergic patients. In a reciprocal inhibition experiment, Cup s 7 completely outcompeted IgE binding to Pru p 7 while only modest inhibition of IgE binding to Cup s 7 by Pru p 7 occurred. These results suggest that Cup s 7 act as the predominant primary sensitizer in cypress pollen associated food allergy.
In a study conducted in Japan, Inomata et. al. studied fruit allergic patients who were not sensitized to the allergens PR 10, profilin or LTP. Out of 100 consecutive peach allergic patients, 20 patients were negative the PR 10 and profilin, indicating true fruit allergy. In this group, 13 patients were sensitized to Pru p 7 and one to LTP. In the Pru p 7 sensitized group, peach (92.3%), apricot (61.5%), orange (46.2%) and apple (30.8%) were the causative fruits, 10 patients reacted to multiple fruits. The authors concluded that the prevalence of GRP (Pru p 7) sensitization was high in the group of Japanese fruit allergic patients whose reactions were not caused by the PR 10, LTP or profilin.
Clinical Relevance
Typical peach-induced clinical symptoms related to Pru p 7 sensitization are severe reactions including anaphylaxis with urticaria, swelling of the face and eyelids and laryngeal tightness. Eyelid swelling has been proposed as a predictive factor for sensitization to Pru p 7 in peach allergy.
Diagnostics
Disease severity
Sensitivity to Pru p 7 has been suggested as a risk factor for severe fruit-induced allergic reactions and the severity of reactions have been found to be significantly associated with the level of sIgE. Furthermore, sensitivity to Pru p 7 may be a characteristic of a sub-type of cypress (Cupressaceae) pollen allergy, in which cypress pollen is the primary sensitizer, causing severe peach allergy.
Testing of specific IgE to Pru p 7 may also be useful in order to fill the diagnostic gap observed in peach allergic patients not sensitized to the peach allergens Pru p 1 (PR-10), Pru p 3 (LTP) and Pru p 4 (profilin), a situation that seems to be especially common in areas with high cypress pollen exposure.
Pru p 7 and Pru p 3 have similar mass and pI, potentially making complete separation difficult during purification of natural extracts. It has therefor been speculated that Pru p 7 contamination of commercial purified natural Pru p 3 (LTP) skin prick test extracts may give rise to reported inconsistent diagnostic results. Using a recombinant molecule may resolve this.
Cross-reactivity
Pru p 7 is a gibberlin-regulated protein (GRP) and, homologous, IgE cross-reactive proteins exists in several fruits of the Rosaceae and Rutaceae families. IgE-mediated cross-reactivity between the fruit GRPs Pru p 7, Pru m 7 (Japanese apricot), Cit s 7 (orange) and Pun g 7 (pomegranate), have been shown. Furthermore, high IgE-mediated cross-reactivity between Pru p 7 and the GRP BP14, present in pollens of the Cupressaceae family, has been shown to be of clinical importance. In a recent study, Ehrenberg et al showed that the Pru p 7 cross-reactive allergen of Cupressaceae pollen is a 7 kDa protein belonging to the GRP family, named Cup s 7.
AIT prescription
There is currently no licensed AIT product for treatment of Pru p 7 (or GRP) induced food allergy. Sublingual AIT for Cypress pollen induced allergic rhinitis exists in some markets but there is currently no evidence that this therapy would alleviate food allergy symptoms caused by GRPs.
Cross-Reactivity
Pru p 7 IgE cross-reactive proteins exists in several fruits of the Rosaceae, (e. g. Japanese apricot, pomegranate) and Rutaceae families (e. g. orange) as well as in pollens from the Cupressaceae family. In a recent study, Ehrenberg et al showed that the Pru p 7 cross-reactive allergen of Cupressaceae pollen is a 7 kDa protein belonging to the gibberlin-regulated protein (GRP) family, named Cup s 7.
References
- Klingebiel, C., et al., Pru p 7 sensitization is a predominant cause of severe, cypress pollen-associated peach allergy. Clin Exp Allergy, 2019. 49(4): p. 526-536.
- Ehrenberg, A.E., et al., Characterization of a 7 kDa pollen allergen belonging to the gibberellin-regulated protein family from three Cupressaceae species. Clin Exp Allergy, 2020.
- Inomata, N., M. Miyakawa, and M. Aihara, Gibberellin-regulated protein in Japanese apricot is an allergen cross-reactive to Pru p 7. Immun Inflamm Dis, 2017. 5(4): p. 469-479.
- Tuppo, L., et al., Pomegranate Cultivars: Identification of the New IgE-Binding Protein Pommaclein and Analysis of Antioxidant Variability. J Agric Food Chem, 2017. 65(13): p. 2702-2710.
- Inomata, N., et al., Identification of gibberellin-regulated protein as a new allergen in orange allergy. Clin Exp Allergy, 2018. 48(11): p. 1509-1520.
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- Tuppo, L., et al., Peamaclein--a new peach allergenic protein: similarities, differences and misleading features compared to Pru p 3. Clin Exp Allergy, 2013. 43(1): p. 128-40.
- Inomata, N., Gibberellin-regulated protein allergy: Clinical features and cross-reactivity. Allergol Int, 2020. 69(1): p. 11-18.
- Inomata, N., M. Miyakawa, and M. Aihara, Eyelid edema as a predictive factor for sensitization to Pru p 7 in peach allergy. J Dermatol, 2016. 43(8): p. 900-5.
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- Senechal, H., et al., Pollen/Fruit Syndrome: Clinical Relevance of the Cypress Pollen Allergenic Gibberellin-Regulated Protein. Allergy Asthma Immunol Res, 2019. 11(1): p. 143-151.
- Poncet, P., T. Aizawa, and H. Senechal, The subtype of Cupressaceae pollinosis associated with Pru p 7 sensitization is characterized by a sensitization to a cross-reactive gibberellin-regulated protein in cypress pollen: BP14. Clin Exp Allergy, 2019. 49(8): p. 1163-1166.