Component-resolved diagnosis of peach allergy and its relationship with prevalent allergenic pollens in China

Abstract

Today, molecule-based component-resolved diagnosis is more commonly used because of its advantage in distinguishing species-specific allergens from cross-reactive allergens and predicting the potential risk of severe reactions. Sensitization patterns of foods comprising the component allergens and relevant manifestations exhibit obvious geographic differences.1Vereda A. van Hage M. Ahlstedt S. Ibanez M.D. Cuesta-Herranz J. van Odijk J. et al.Peanut allergy: Clinical and immunologic differences among patients from 3 different geographic regions.J Allergy Clin Immunol. 2011; 127: 603-607Abstract Full Text Full Text PDF PubMed Scopus (222) Google Scholar, 2Andersen M.B. Hall S. Dragsted L.O. Identification of European allergy patterns to the allergen families PR-10, LTP, and profilin from Rosaceae fruits.Clin Rev Allergy Immunol. 2011; 41: 4-19Crossref PubMed Scopus (49) Google Scholar Peach allergy is common in China; however, the sensitization to peach allergens and the relevance of the sensitization pattern for the clinical presentation remain unclear. The most important peach allergens, Pru p 1, Pru p 3, and Pru p 4, belong to the protein family of pathogenesis-related protein 10 (PR-10), nonspecific lipid transfer protein (nsLTP), and profilin, respectively. It is well known that PR-10–related oral allergy syndrome usually follows birch pollen sensitization.2Andersen M.B. Hall S. Dragsted L.O. Identification of European allergy patterns to the allergen families PR-10, LTP, and profilin from Rosaceae fruits.Clin Rev Allergy Immunol. 2011; 41: 4-19Crossref PubMed Scopus (49) Google Scholar The nsLTPs used to be considered pollen-unrelated “true” food allergens. However, Platanus acerifolia, Olea europaea, and mugwort pollen nsLTPs were successively reported to have a close relationship with peach nsLTP, namely Pru p 3,3Lombardero M. Garcia-Selles F.J. Polo F. Jimeno L. Chamorro M.J. Garcia-Casado G. et al.Prevalence of sensitization to Artemisia allergens Art v 1, Art v 3 and Art v 60 kDa. Cross-reactivity among Art v 3 and other relevant lipid-transfer protein allergens.Clin Exp Allergy. 2004; 34: 1415-1421Crossref PubMed Scopus (132) Google Scholar, 4Enrique E. Cistero-Bahima A. Bartolome B. Alonso R. San M.M. Bartra J. et al.Platanus acerifolia pollinosis and food allergy.Allergy. 2002; 57: 351-356Crossref PubMed Scopus (76) Google Scholar, 5Florido L.J. Quiralte E.J. Arias D.S.A.J. Saenz D.S.P.B. Martin C.E. An allergen from Olea europaea pollen (Ole e 7) is associated with plant-derived food anaphylaxis.Allergy. 2002; 57: 53-59Crossref Scopus (3) Google Scholar despite the controversy on the initiation pathway of primary sensitization.3Lombardero M. Garcia-Selles F.J. Polo F. Jimeno L. Chamorro M.J. Garcia-Casado G. et al.Prevalence of sensitization to Artemisia allergens Art v 1, Art v 3 and Art v 60 kDa. Cross-reactivity among Art v 3 and other relevant lipid-transfer protein allergens.Clin Exp Allergy. 2004; 34: 1415-1421Crossref PubMed Scopus (132) Google Scholar, 6Pastorello E.A. Pravettoni V. Farioli L. Rivolta F. Conti A. Ispano M. et al.Hypersensitivity to mugwort (Artemisia vulgaris) in patients with peach allergy is due to a common lipid transfer protein allergen and is often without clinical expression.J Allergy Clin Immunol. 2002; 110: 310-317Abstract Full Text Full Text PDF PubMed Scopus (85) Google Scholar, 7Lauer I. Miguel-Moncin M.S. Abel T. Foetisch K. Hartz C. Fortunato D. et al.Identification of a plane pollen lipid transfer protein (Pla a 3) and its immunological relation to the peach lipid-transfer protein, Pru p 3.Clin Exp Allergy. 2007; 37: 261-269Crossref PubMed Scopus (94) Google Scholar Mugwort is the most important allergenic pollen allergen in late summer and autumn in China, especially in the northern region, where pollinosis is a major health problem.8Ye S.T. Zhang J.T. Gu R.J. Investigation of aeroborne allergenic pollens in different regions of China.1st ed. Peking Publishing House, Beijing1991Google Scholar A very recent study from China concluded that Art v 3 played a dominant role in peach allergy as a primary sensitizer.9Gao Z.S. Yang Z.W. Wu S.D. Wang H.Y. Liu M.L. Mao W.L. et al.Peach allergy in China: a dominant role for mugwort pollen lipid transfer protein as a primary sensitizer.J Allergy Clin Immunol. 2013; 131 (e1-3): 224-226Abstract Full Text Full Text PDF PubMed Scopus (73) Google Scholar Here we present sensitization patterns of peach and their clinical significance in China and further analyze the relationship between pollen sensitization and peach allergy. Eighty-seven patients with positive peach-specific IgE levels were included in this study. Thirty-eight were symptomatic on peach exposure (19 only presented with oral allergy syndrome, which consists of isolated oropharyngeal symptoms, and 19 had ≥1 after manifestations: generalized urticaria, allergic rhinitis, asthma, gastrointestinal symptoms, or even hypotension with or without oral reactions). Forty-nine patients were sensitized but tolerant to peach (peach-tolerant group). Total IgE and specific IgE against peach, rPru p 1 and rPru p 3, rBet v 1, rBet v 2, mugwort, and nArt v 3 were detected by using the ImmunoCAP system (Thermo Fisher, Uppsala, Sweden). Because Pru p 4 reactivity was proved to be completely correlated with Bet v 2, we tested rBet v 2 (birch profilin) instead of rPru p 4. This research protocol was approved by the local ethics committee, and written consent was obtained from each patient. All patients were from northern China, where mugwort and birch are 2 of the most common allergenic pollens that lead to seasonal rhinitis, asthma, or both in late summer and autumn, as well as spring, respectively.8Ye S.T. Zhang J.T. Gu R.J. Investigation of aeroborne allergenic pollens in different regions of China.1st ed. Peking Publishing House, Beijing1991Google Scholar There were no differences in sex, age, family history of allergic disease, personal history of eczema or drug allergy, and total IgE levels between symptomatic and asymptomatic patients (Table I). Peach-specific IgE levels of symptomatic patients were markedly higher than those of asymptomatic patients (median, 6.11 vs 2.68 kU/L; P = .023; Table I).Table IClinical characteristics and sensitization profiles of patients included in this studyCharacteristicsSymptomatic patients (n = 38)Asymptomatic patients (n = 49)P valueMale sex, no. (%)15 (39.5)23 (46.9).517Age, median (range)24.5 (6-49)26 (2-49).264Positive family history of atopy, no. (%)16 (42.1)21 (42.9)1.000Total IgE (kUA/L), median (range)219.5 (24.4-5000)273 (16.6-2643).691Peach-specific IgE (kUA/L), median (range)6.11 (0.39-64.1)2.68 (0.32-18.5).023Other known food allergies, no. (%)38 (100.0)31 (63.3)<.001Atopic eczema3 (7.9)5 (10.2)1.000Drug allergy, no. (%)14 (36.8)16 (32.7).821Pollens, no. (%) Birch symptoms17 (44.7)13 (26.5).076ImmunoCAP32 (84.2)32 (65.3).047 rBet v 119 (50.0)12 (24.5)<.001 Mugwort symptoms18 (47.4)29 (59.2).270ImmunoCAP26 (68.4)41 (83.7).094 nArt v 317 (44.7)25 (51.0).233 Other symptoms8 (21.1)13 (26.5).554ImmunoCAP6 (15.8)8 (16.3)1.000Sensitization profile of peach, no. (%) rPru p 114 (36.8)5 (10.2).003 rPru p 1 + rBet v 201 (2.0)ND rPru p 1 + rPru p 33 (7.9)4 (8.2)1.000 rPru p 1 + rPru p 3 + rBet v 21 (2.6)0 ND rPru p 38 (21.1)14 (28.6).424 rPru p 3 + rBet v 29 (23.7)6 (12.2).161 rBet v 23 (7.9)11 (22.4).067 Other08 (16.3)ND Total rPru p 118 (47.4)10 (20.4).008 Total rPru p 321 (55.3)24 (49.0).561 Total rBet v 213 (34.2)18 (36.7).807SS (n = 19)OAS (n = 19)Pollens, no. (%) Birch symptoms5 (26.3)12 (63.2).022ImmunoCAP17 (89.5)15 (78.9).374 rBet v 16 (31.6)13 (68.4).023 rBet v 211 (57.9)2 (10.5).002 Mugwort symptoms12 (63.2)6 (31.6).051ImmunoCAP16 (84.2)10 (52.6).036 nArt v 313 (68.4)4 (21.1).003Sensitization patterns of peach, no. (%) rPru p 13 (15.8)11 (57.9).007 rPru p 1 + rPru p 31 (5.2)2 (10.5)ND rPru p 1 + rPru p 3 + rBet v 201 (5.2)ND rPru p 34 (21.1)4 (21.1)1.000 rPru p 3 + rBet v 29 (47.4)0ND rBet v 22 (10.5)1 (5.2)ND Total rPru p 14 (21.1)14 (73.7).005 Total rPru p 314 (73.7)7 (36.8).022 Total rBet v 211 (57.9)2 (10.5).002Comparison of categorical variables between groups was conducted by using the Pearson χ2 or Fisher exact tests. Cutoff values for positive ImmunoCAP results were 0.35 kU/L for specific IgE antibodies against extracts of pollens and peach and 0.30 kU/L for specific IgE antibodies against allergenic components of pollens and peach.ND, Not determined because of a small number of patients; OAS, oral allergy syndrome; SS, systemic symptoms. Open table in a new tab Comparison of categorical variables between groups was conducted by using the Pearson χ2 or Fisher exact tests. Cutoff values for positive ImmunoCAP results were 0.35 kU/L for specific IgE antibodies against extracts of pollens and peach and 0.30 kU/L for specific IgE antibodies against allergenic components of pollens and peach. ND, Not determined because of a small number of patients; OAS, oral allergy syndrome; SS, systemic symptoms. The total positivity rate of IgE response to rPru p 1, rPru p 3, and rBet v 2 was 47.4%, 55.3%, and 34.2% in the symptomatic group, respectively (Table I), and therefore rPru p 3 was the major allergen of peach in our population. The 3 most common sensitization patterns of peach were monosensitization to rPru p 1, cosensitization to rPru p 3 and rBet v 2, and monosensitization to rPru p 3, which involved 81.6% of all patients with peach allergy (Table I). Although no differences were found in the prevalence of birch pollinosis between symptomatic and asymptomatic patients, birch pollen sensitization, as represented by positivity for serum IgE (using 0.35 kU/L as a cutoff), was more common in the symptomatic group than in the asymptomatic group (84.2% vs 65.3%, respectively; P = .047), as was specific IgE against rBet v 1 (Table I). Moreover, rPru p 1 IgE levels were significantly related to rBet v 1 levels (Spearman ρ = 0.934; P < .001). This might be a reasonable explanation for the higher positivity rate of IgE response to rPru p 1 in the symptomatic group (Table I). Therefore rPru p 1 was a clinically relevant allergen of peach in our population. Furthermore, rPru p 1 sensitization was more frequently observed in the subgroup with oral allergy syndrome, which was most likely due to the higher prevalence of birch pollinosis and rBet v 1 sensitization in the oral allergy syndrome subgroup (Table I). The prevalence of mugwort pollinosis and pollen sensitization did not differ between symptomatic and asymptomatic patients, but mugwort pollen sensitization did affect the types of symptoms of peach allergy (Table I). Mugwort pollen and nArt v 3 sensitization was more frequently seen in patients with systemic symptoms, which was in accordance with the higher frequency of rPru p 3 sensitization in the SS group. Art v 3 IgE levels were also in close relationship with rPru p 3 IgE levels (Spearman ρ = 0.718, P < .001). Comparisons of rPru p 3 and nArt v 3 IgE levels were conducted between rPru p 3–sensitized patients with and without relevant clinical symptoms to further analyze the relationship of mugwort pollinosis with peach allergy. A total of 45 patients were sensitized to rPru p 3 in this study, but only 21 patients presented with relevant manifestations (rPru p 3 allergy), among whom 13 patients also had mugwort pollinosis and the remaining 8 patients only had peach allergy. In addition, 15 of the 24 rPru p 3–sensitized but tolerant patients (rPru p 3 tolerance) had mugwort pollinosis, and the remaining 9 patients were free of both peach allergy and mugwort pollinosis. Mugwort pollinosis was defined as seasonal rhinitis, asthma, or both occurring only in late summer and autumn, together with a confirmed positive serum IgE response to mugwort pollen extract. No difference was found in rPru p 3 IgE levels between the patients with rPru p 3 allergy and the tolerant patients (median, 2.32 vs 2.43 kU/L; P = .724). Art v 3 levels were remarkably higher than rPru p 3 levels in patients with mugwort pollinosis, whereas rPru p 3 IgE levels were comparable with Art v 3 IgE levels in patients without mugwort pollinosis (Fig 1). No significant difference in nArt v 3 IgE levels was found between patients with mugwort allergy with and without peach allergy (median, 40.70 vs 15.10 kU/L, respectively; P = .107). Of the patients allergic to both peach and mugwort pollen, 84.6% (11/13) of the patients had peach-related adverse reactions approximately 4 years (range, 1-7 years) after the occurrence of seasonal respiratory symptoms, and only 2 patients were allergic to peach starting early in life. The duration (in years) of mugwort pollinosis of rPru p 3–sensitized but tolerant patients was comparable with that of patients with rPru p 3 allergy (median, 7 years [range, 2-15 years] vs 5 years [range, 2-20 years]; P = .266). Using an ImmunoCAP inhibition method, Gao et al9Gao Z.S. Yang Z.W. Wu S.D. Wang H.Y. Liu M.L. Mao W.L. et al.Peach allergy in China: a dominant role for mugwort pollen lipid transfer protein as a primary sensitizer.J Allergy Clin Immunol. 2013; 131 (e1-3): 224-226Abstract Full Text Full Text PDF PubMed Scopus (73) Google Scholar showed that a prevalent group of Chinese patients with peach allergy were primarily sensitized to mugwort and concluded that mugwort Art v 3 plays a dominant role in peach allergy as a primary sensitizer. With a different study design, we found that less than half of the patients with peach allergy had mugwort pollinosis and that a relatively small proportion of patients with mugwort pollinosis with IgE positivity for peach also presented with peach-related clinical symptoms. The duration of mugwort pollinosis in patients without peach allergy was comparable with that seen in those with peach allergy and longer than the duration within which peach allergy was expected to occur. These results indicated that this larger proportion of patients would most likely not have peach allergy later in life, and therefore it is premature to state that mugwort pollinosis has a dominant role in the development of peach allergy. However, patients with mugwort pollinosis had remarkably higher IgE levels for nArt v 3 relative to rPru p 3, and nArt v 3 IgE levels had a good correlation with rPru p 3 IgE levels. Thus we postulate that mugwort pollinosis increases the risk of sensitization to rPru p 3, but this sensitization does not necessarily translate into clinical allergy. Another interesting finding of our study was that profilin (rBet v 2) seemed to remarkably increase the risk of systemic symptoms in our population. Previous studies have shown that Pru p 3 was associated with generalized and severe symptoms, whereas reactions caused by profilin sensitization are usually restricted to the oral cavity because of its sensitivity to heat denaturation and gastric digestion. In our study only half of the patients (4/8) monosensitized to Pru p 3 presented with systemic reactions, whereas 100% of the patients (9/9) cosensitized to Pru p 3 and Bet v 2 had systemic symptoms on peach ingestion. In other words, the risk of systemic reactions was significantly higher in patients cosensitized to Pru p 3 and Bet v 2 than in patients monosensitized to rPru p 3 (50% vs 100%, P = .029). Ethnic variation partly accounts for this difference, and further studies on this topic might be insightful. In contrast to the situation in Europe, grass pollinosis is relatively rare in our country.8Ye S.T. Zhang J.T. Gu R.J. Investigation of aeroborne allergenic pollens in different regions of China.1st ed. Peking Publishing House, Beijing1991Google Scholar Instead, mugwort was the predominant allergenic pollen, and all but 1 patient sensitized to Bet v 2 were also sensitized to mugwort pollen. Moreover, 11 of 13 patients sensitized to Bet v 2 were in the subgroup with systemic symptoms, which is in line with the mugwort sensitization profile. Therefore we hypothesize that mugwort pollen might be the primary source of profilin sensitization in northern China. To date, our study is the most comprehensive evaluation of peach allergy in China performed combining molecular diagnosis with the clinical phenotype and relevant pollen allergy. The biggest limitation of our work was that the diagnosis of peach allergy was based on a convincing history and positive serum-specific IgE level against peach, as well as its allergenic components, rather than a double-blinded, placebo-controlled, food challenge test result, for the purpose of avoiding the potential risk of severe adverse reactions in the tough medical environment that currently exists in China. However, all of the patients received diagnoses by an experienced allergist, and the clinical data were carefully collected by another doctor independently using a uniform questionnaire. Therefore the conclusion of this study is objective and convincing. We thank all of the participants involved in this study and also Dr Peipei Cai for assisting with the IgE tests.