Pru p 4
Summary
The peach allergen, Pru p 4, is a profilin, which can act as an actin-binding protein. Peach profilin is one of the important pan-allergens. Pru p 4 in peach is reported to share similar amino-acid sequence with profilins from other members of the Rosaceae family, such as apple and cherry. It can also cross-react with profilin in pollens from unrelated families such as Artemisia vulgaris, Betula alba, Corylus avellanus, P amygdalus. Pollen food allergy syndrome (PFAS) is found to occur due to cross-reactivity between Pru p 4 and profilins present in trees, grass, and other weeds. Typically, Pru p 4 is found to be associated with mild symptoms of oral allergy syndrome (OAS). Pru p 4 was identified as a marker allergen for predicting non-systemic symptoms in peach allergy.
Epidemiology
Worldwide distribution
Pru p 4 in peach is a profilin which is an important pan-allergen found in various pollen and vegetable sources. A prospective cross-sectional study in Spain among 57 children identified Pru p 4 in peach as a minor allergen as the sensitization to Pru p 4 was quite low (10% of 39). A cross-sectional study on 148 peach allergic patients from Italy showed that 40.8% (31/76) patients with Pru p 4 sensitivity showed mild OAS. Another study in Japan involving 27 peach allergic patients showed that Pru p 4 sensitization resulted in oral allergy symptoms. Furthermore, a retrospective study in Japan using 90 patients with peach allergy showed that sIgE to Pru p 4 was negatively associated with the occurrence of systemic symptoms due to peach.
Clinical Relevance
Disease Severity
A cross-sectional observational study in 148 peach-allergic individuals identified that Pru p 4 sensitivity is usually associated with mild symptoms of oral allergy syndrome (OAS) pertaining to the oral mucosa. In this study, around 41% (n=76) of patients had mild OAS symptoms while 18% (n=72) of patients suffered with severe OAS symptoms due to Pru p 4 sensitivity.
A study by Inomata et al. (2017) in Japan identified PFAS in most of the patients (80% of 100) either due to Pru p 1 and/or Pru p 4 sensitivity.
Cross-reactive molecules
PFAS can arise due to cross-reactivity between Pru p 4 in peach and profilins in tree, grass, and weed pollen. Although, alder pollen might be the primary contributor for oral symptoms in peach allergic patients with Pru p 1 and/or Pru p 4 sensitization.
In a prospective, cross-sectional study by Boyano-Martinez et al. (2013) a patient with positive Pru p 4 antibodies had reported similar symptoms of OAS with melon, watermelon, and pear. This could be due to the wide distribution of profilins in various pollens and fruits.
Diagnostics
Disease Severity
A prospective study carried in 29 peach allergic patients pointed that individuals with a positive Pru p 4.01 but negative skin prick test (SPT) to Pru p 3 experienced more OAS symptoms and lesser systemic reactions than those with negative Pru p 4.01 and positive Pru p 3. Evidence suggest that co-sensitization of Pru p 3, Pru p 1, and/or Pru p 4 among peach allergic patients may provide a shield against severe symptoms due to Pru p 3.
A retrospective study with 90 peach allergic children in Japan concluded that sIgE of Pru p 4 was an accurate predictor (100% specificity and 61% sensitivity) of non-systemic peach allergy.
Cross-reactivity
Rodriguez-Perez et al. (2003) identified in their study with 29 patients that all 15 sera with positive Bet v 2 reacted with Pru p 4 isoallergen (Pru p 4.01). Whereas no sera reacted with Pru p 4.01 in 14 patients without IgE antibodies to birch profilin. Thus, implying that sIgE to birch profilin (Bet v 2) can act as a diagnostic marker for detecting sensitivity to Rosaceae fruit profilins.
Exposure
The main exposure route for this allergen is through ingestion.
Cross-Reactivity
The Pru p 4 variants displayed about 80% similarity in their amino acid sequences. Pru p 4.0101 showed more than 90% sequence similarity to profilins from other Rosaceae fruits, such as cherry and apple. Pru p 4.0201 showed more than 70% similarity to amino acid sequence from botanically unrelated foods such as soybean and carrot and pollens such as birch and sunflower. A comparative study by Cuesta-Herranz et al. (1999) identified that cross-reactivity between peach profilins and botanically unrelated pollens (Artemisia vulgaris, Betula alba, Corylus avellanus, P amygdalus) exists. A recent study also showed that cross reactivity between a muskmelon profilin (Cuc m 2.0101) and Pru p 4.0101 exists due to similar amino acid sequence and identity. Additionally, a melon profiling study identified that profilin’s IgE cross reactivity depends more on the conformational structure than the amino acid sequence similarity rate.
References
- Cuesta-Herranz J, Lazaro M, Martinez A, Figueredo E, Palacios R, de-Las-Heras M, et al. Pollen allergy in peach-allergic patients: sensitization and cross-reactivity to taxonomically unrelated pollens. J Allergy Clin Immunol. 1999;104(3 Pt 1):688-94.
- Boyano-Martinez T, Pedrosa M, Belver T, Quirce S, Garcia-Ara C. Peach allergy in Spanish children: tolerance to the pulp and molecular sensitization profile. Pediatr Allergy Immunol. 2013;24(2):168-72.
- Pastorello EA, Farioli L, Pravettoni V, Scibilia J, Mascheri A, Borgonovo L, et al. Pru p 3-sensitised Italian peach-allergic patients are less likely to develop severe symptoms when also presenting IgE antibodies to Pru p 1 and Pru p 4. Int Arch Allergy Immunol. 2011;156(4):362-72.
- Ando Y, Miyamoto M, Kato M, Nakayama M, Fukuda H, Yoshihara S. Pru p 7 Predicts Severe Reactions after Ingestion of Peach in Japanese Children and Adolescents. Int Arch Allergy Immunol. 2020;181(3):183-90.
- Asaumi T, Sato S, Yanagida N, Takahashi K, Mori Y, Okazaki F, et al. IgE-specific Pru p 4 negatively predicts systemic allergy reaction to peach among Japanese children. Allergol Int. 2019;68(4):546-8.
- Inomata N, Miyakawa M, Aihara M. High prevalence of sensitization to gibberellin-regulated protein (peamaclein) in fruit allergies with negative immunoglobulin E reactivity to Bet v 1 homologs and profilin: Clinical pattern, causative fruits and cofactor effect of gibberellin-regulated protein allergy. J Dermatol. 2017;44(7):735-41.
- Rodriguez-Perez R, Fernandez-Rivas M, Gonzalez-Mancebo E, Sanchez-Monge R, Diaz-Perales A, Salcedo G. Peach profilin: cloning, heterologous expression and cross-reactivity with Bet v 2. Allergy. 2003;58(7):635-40.
- Botton A, Andreotti C, Costa G, Ramina A. Peach ( Prunus persica L. Batsch) Allergen-Encoding Genes Are Developmentally Regulated and Affected by Fruit Load and Light Radiation. J Agric Food Chem. 2009;57(2):724-34.
- WHO/IUIS. Pru p 4 - International Union of Immunological Societies Allergen Nomenclature 2019 [29-Dec-2020]. Available from: http://www.allergen.org/viewallergen.php?aid=559.
- Kapingidza AB, Pye SE, Hyduke N, Dolamore C, Pote S, Schlachter CR, et al. Comparative structural and thermal stability studies of Cuc m 2.0101, Art v 4.0101 and other allergenic profilins. Mol Immunol. 2019;114:19-29.
- Asero R, Barber D. C01. PROFILINS. In: Matricardi P. M., Kleine-Tebbe J., Hoffmann H. J. ea, editors. Molecular Allergology User's Guide. Switzerland: The European Academy of Allergy and Clinical Immunology (EAACI); 2016. p. 293-8.
- Yang Z, Ma Y, Chen L, Xie R, Zhang X, Zhang B, et al. Differential transcript abundance and genotypic variation of four putative allergen-encoding gene families in melting peach. Tree Genet Genom. 2011;7(5):903-16.
- Sankian M, Varasteh A, Pazouki N, Mahmoudi M. Sequence homology: a poor predictive value for profilins cross-reactivity. Clin Mol Allergy. 2005;3:13.
- Uasuf CG, Villalta D, Conte ME, Di Sano C, Barrale M, Cantisano V, et al. Different co-sensitizations could determine different risk assessment in peach allergy? Evaluation of an anaphylactic biomarker in Pru p 3 positive patients. Clin Mol Allergy. 2015;13:30.