Pru p 7 Sensitisation in Northern China: High Prevalence and Wide Cross‐Reactivity

Peach is among the most prevalent allergenic fruits in China [1], and six allergens have been identified to date (www.allergen.org; www.allergome.org): Pru p 1, Pru p 2, Pru p 3, Pru p 4, Pru p 7 (gibberellin-regulated protein, GRP) and Pru p 9 (in pollen). Over the past decade, continuous investigation into the allergenicity of Pru p 7 has led to its recognition as a significant risk factor for severe peach allergy, with a high prevalence in southern France and Japan, and lower prevalence in Spain [2-4]. Additionally, high sequence identity and extensive cross-reactivity among GRP allergens have been reported in various plants, including cypress pollen, peach and fruits from the Rosaceae and Rutaceae families, with clinical manifestations such as oral symptoms, urticaria and angioedema [5]. Recently, several cases of allergy to Pru p 7 have been reported in China [6]. As its potential for sensitisation in a broader population remains unknown, we conducted this study on a large cohort of Chinese patients with peach allergy to investigate the allergenicity and cross-reactivity of Pru p 7. A total of 536 outpatients from Henan Provincial People's Hospital (Zhengzhou, Henan Province), reporting peach allergy, were recruited between January 2022 and July 2024. They were classified into three groups: 88 cases aged ≤ 12 years, 30 cases aged 13–18 and 418 cases aged > 18 years. 21.8%, 23.1% and 9.0% of them tested positive for sIgE to mugwort, rape and cypress pollen, respectively. Written informed consent was obtained from all participants, and the study was approved by the Ethics Committee of the School of Life Sciences, Zhengzhou University (approval No. GZR2022-1744). Through further ELISA testing with rPru p 7, 278 rPru p 7–positive individuals were identified, yielding a positive rate of up to 51.87% (278/536). A significant difference was observed in serum sIgE-binding levels between the crude extract and Pru p 7 (Figure 1A, p < 0.0001), with 39 patients having substantially higher levels than the crude extract (n = 239), suggesting that these patients had a strong allergic reaction to Pru p 7. A significant variation in Pru p 7 positivity was observed among the three age groups, with the highest rate in the paediatric group, progressively decreasing with increasing age (Figure 1B, p < 0.0001), similar to the findings for Pru p 3 reported by Tosca et al. [7]. To investigate the potential cross-reactivity of Pru p 7, nine types of fruits and pollens—peach, apple, cherry, orange, pomegranate, strawberry, cypress, mugwort and rape pollen—were tested by ELISA inhibition using eight different Pru p 7–positive serum pools. Each serum pool consisted of individuals with concurrent allergies to both the tested species and peach Pru p 7. Since the content of GRP proteins in different plants may affect their cross-reactivity, quantitative analysis of the GRP content in the corresponding plants was completed. A detailed description of the methods and results is available in the following repository: https://osf.io/unp52/?view_only=02d80661561d433eb7bf745837ce9374. The ELISA inhibition rate of the three pollens for rPru p 7 was higher than that of fruits, aligning with the measured GRP levels, except for pomegranate. This suggests that the GRP level is a critical factor influencing inhibition and GRP proteins may play an important role in cross-reactivity between peach and the tested fruits/pollens. Despite having a lower GRP level compared to the three pollens, the inhibition rate for pomegranate (59.0%) was second only to that of peach (75.9%) (Figure 1C), suggesting that the IgE-binding epitope of the pomegranate GRPs may be more similar to Pru p 7. These findings suggest that widespread cross-reactivity among Pru p 7, fruits and pollens is also a common phenomenon in China. Additionally, a subset of 76 patients with high OD values for peach extract (from high to low) among peach extract–positive individuals (n = 536) was selected and subjected to further testing with four allergens: rPru p 1, nPru p 3, rPru p 4 and rPru p 7. A significant variation in their sensitisation rates was observed. The average OD value for Pru p 3 was the highest (OD = 0.21), while the percentage of patients sensitised to Pru p 7 was the highest (50%) (Figure 1D). These findings suggest that Pru p 3 and Pru p 7 are the most clinically significant allergens in northern China. The limitations of this study are mainly due to the limited regions that prevented a more comprehensive survey of the whole country. Previous research has demonstrated cross-reactivity between cypress pollen and peach [3, 8, 9]. In Zhengzhou, located in northern China, cypress trees are widely distributed along roads and in parks, potentially exacerbating Pru p 7 allergy. Although these findings are important for peach allergic diagnosis, further research is necessary to explore the relationship of Pru p 7, clinical symptoms and the impact of these sensitisation patterns on disease severity. In conclusion, Pru p 7 is a major peach allergen in northern China, with moderate IgE-binding capacity and a high Pru p 7–positive rate of 51.9%, compared to 41% for Pru p 3. Extensive cross-reactivity was observed among Pru p 7, fruits, and the pollens of mugwort, cypress and rape. Given its high sensitisation rate and extensive cross-reactivity, it is crucial to emphasise the clinical significance of Pru p 7 in the diagnosis of peach allergies in China. Additional information on study methods and findings is available in the following repository: https://osf.io/unp52/?view_only=02d80661561d433eb7bf745837ce9374. Jing Jin, Zhongshan Gao and Jinyong Huang conceived and planned the study. Bingjie Chen and Bingyang Zhou carried out experiments and data analyses. Siqin Wang, Jianbo Wang, Pengfei Ba, Xu Wang and Jie Jin provided the serums. Lan Zhao provided peach allergens rPru p 1, nPru p 3 and rPru p 4. Bingjie Chen, Jing Jin and Zhongshan Gao wrote the manuscript. All authors read and approved the final manuscript. We thank our patients for providing their serum in our study. This study was funded by the National Natural Science Foundation of China (grant 32202450) and China Postdoctoral Science Foundation (grant 2022 M722897). This work was supported by the National Natural Science Foundation of China (Grant 32202450), China Postdoctoral Science Foundation (Grant 2022M722897). The study was approved by the Ethics Committee of the School of Life Sciences, Zhengzhou University (Authorisation No. GZR2022-1744). Written informed consent was obtained from all participants. The authors declare no conflicts of interest. The data that support the findings of this study are openly available in OSF at https://osf.io/unp52/?view_only=02d80661561d433eb7bf745837ce9374.