Allergy to Gibberellin-Regulated Proteins (Peamaclein) in Children.

BACKGROUND: Gibberellin-regulated proteins (GRPs, Peamaclein) are allergens recently identified in plant-derived food allergy (FA), and little is known about the clinical manifestations of this allergic condition in the European population, especially in children. OBJECTIVE: Our study aimed to identify and characterize pediatric patients with pollen-FA due to GRP sensitization. METHODS: We retrospectively analyzed the charts of patients referred to the Allergy Unit of the Meyer Children's Hospital in Florence for suspected FA. Three main eligibility criteria based on the actual knowledge of GRP allergy were used to select patients deserving further investigations: (1) systemic reactions after consumption of fruit or an unknown culprit food, (2) positive skin prick tests to both cypress pollen and Pru p 3-enriched peach peel extracts, (3) negative in vitro test results for Pru p 3 serum-specific Immunoglobulin E (sIgE). We performed the in vitro test to determine the anti-rPru p 7 (Peamaclein) sIgE levels in the selected patients. RESULTS: We identified 10 pediatric patients with Pru p 7 allergy and described their characteristics. The use of our eligibility criteria showed a high accuracy in identifying these patients: 100% of the selected patients had positive in vitro results for Pru p 7. We therefore proposed a diagnostic algorithm for Pru p 7 allergy. CONCLUSION: This is the first case series of European pediatric patients with a demonstrated Peamaclein allergy. These findings broaden our knowledge on GRP allergy in pediatric populations and could help clinicians to suspect, diagnose, and manage this recently discovered plant-derived FA.

Cloning and immunobiochemical analyses on recombinant chymopapain allergen Cari p 2 showing pollen-fruit cross-reaction.

Papaya is reported to trigger food and respiratory allergy. Here, we identified chymopapain Cari p 2 as an allergen that can sensitize atopic individuals through fruit consumption followed by respiratory hazards through pollen exposure. Recombinant Cari p 2 displayed IgE-reactivity with 78% of papaya allergic sera. rCari p 2 also displayed allergenic activity through basophil degranulation. rCari p 2 is correctly folded and showed irreversible denaturation in the melting curve. rCari p 2 displayed IgE-cross-reactivity with homologous cysteine proteases from kiwi and pineapple. Cari p 2 transcript was also detected in papaya pulps. rCari p 2 was resistant to pepsin digestion and retained IgE-reactivity after 60 minutes of pepsin digestion. In mouse model, rCari p 2 was found to elicit inflammatory responses in the lung and gastrointestinal epithelium. Hence, Cari p 2 is a newly characterized allergen with diagnostic and immunotherapeutic potential for managing allergic disorders in papaya sensitized individuals.

Pollen-food allergy syndrome and component sensitization in adolescents: A Japanese population-based study.

Allergic rhino-conjunctivitis with pollen allergy has been prevalent worldwide and Pollen-food allergy syndrome (PFAS) refers to individuals with pollen allergy who develop oral allergy syndrome (OAS) on consuming fruits and vegetables. The prevalence of PFAS varies by region and that in Japanese adolescents remains to be elucidated. In this cross-sectional study, we examined the epidemiological characteristics of PFAS in a general population of Japanese adolescents according to pollen allergy, OAS, and IgE component sensitization. Participants comprised adolescents, at age 13 years, from a prospective birth cohort study in Japan. We administered questionnaires to collect information from parents regarding pollen allergy, PFAS and OAS at each child's age 13 years. ImmunoCAP ISAC was used to assess IgE component sensitization. Among 506 participants with a complete questionnaire and ISAC measurement results, 56.5% had a history of hay fever, 16.0% had a history of OAS, 51.0% had pollen allergy, and 11.7% had a history of PFAS; additionally, 72.7% were sensitized to one or more tree, grass, and/or weed allergens. The most common sensitization (95.7%) among adolescents with pollen allergy was to Japanese cedar (Cry j 1). The most common causal foods were kiwi and pineapple (both 39.0%). Knowledge levels about PFAS were poor among affected adolescents. We found a high prevalence of PFAS among adolescents in Japan. Although it affects approximately 1/10 adolescents in the general population, public awareness regarding PFAS is poor. Interventional strategies are needed to increase knowledge and to prevent PFAS in the general population.

Birch Pollen Related Pear Allergy: A Single-Blind Oral Challenge TRIAL with 2 Pear Cultivars.

Approximately 70% of birch pollen allergic patients in Europe experience hypersensitivity reactions to Immunoglobulin E (IgE) cross-reactive food sources. This so-called pollen-food syndrome (PFS) is defined by allergic symptoms elicited promptly by the ingestion of fruits, nuts, or vegetables in these patients. So far, in the literature, less attention has been given to Bet v 1 cross-reactive symptoms caused by pear (Pyrus communis). In the Netherlands, pears are widely consumed. The primary objective of this study was to measure the type and severity of allergic symptoms during pear challenges in birch pollen allergic patients, with a positive history of pear allergy, using two different pear varieties. Fifteen patients were included, skin prick test (SPT), prick-to-prick test (PTP), specific Immunoglobulin E (sIgE), and single-blind oral challenges were performed with two pear (Pyrus communis) varieties: the 'Cepuna' (brand name Migo®) and the 'Conference' pears. All patients were sensitized to one or both pear varieties. A total of 12 out of 15 participants developed symptoms during the 'Cepuna' food challenge and 14/15 reacted during the 'Conference' challenge. Challenges with the 'Cepuna' pears resulted in less objective symptoms (n = 2) in comparison with challenges with 'Conference' pears (n = 7). Although we did not find significance between both varieties in our study, we found a high likelihood of fewer and less severe symptoms during the 'Cepuna' challenges. Consequently selected pear sensitized patients can try to consume small doses of the 'Cepuna' pear outside the birch pollen season.

Can patients with oral allergy syndrome be at risk of anaphylaxis?

PURPOSE OF REVIEW: Oral allergy syndrome, also known as pollen-food syndrome (PFS), is a condition usually associated with adults and characterized by mild transient oropharyngeal symptoms. The purpose of this review is to determine whether systemic or anaphylactic reactions do occur and if so, who is affected and what are the triggers. RECENT FINDINGS: An increasing number of studies demonstrate that PFS occurs all age groups, and a significant number of affected adults do experience systemic and anaphylactic reactions. The upsurge in the adoption of vegan lifestyles, increase in consumption of fruits and vegetables including smoothies and juices, and use of plant foods in nutritional or body-building supplements, could exacerbate this. Changes in pollen and pollution levels, cofactors and sensitization to other plant food allergens may also be involved. SUMMARY: While the majority of those with PFS will continue to experience mild symptoms, all individuals should be properly advised regarding the dangers of concentrated or unusual forms of plant food allergens such as smoothies, juices, soy/nut milks and nutritional supplements. Further well characterized studies are needed to determine risk factors for severe reactions, and sensitization patterns to pollens and plant food allergens.

Terpinen-4-ol Enhances Disease Resistance of Postharvest Strawberry Fruit More Effectively than Tea Tree Oil by Activating the Phenylpropanoid Metabolism Pathway.

This study aimed to reveal the effects and possible mechanism of terpinen-4-ol, the main component of tea tree oil (TTO), on the disease resistance of strawberry fruit. When the effects of TTO and its components were compared on the decay development in fruit inoculated with Botrytis cinerea after treatment, strawberry treated with terpinen-4-ol showed the lowest disease incidence (44.4%) after 48 h and also the smallest lesion diameter during the whole storage. This indicates that terpinen-4-ol induces the highest disease resistance in strawberry compared with TTO and other components. Untargeted metabolomic analysis showed that terpinen-4-ol treatment strongly activated phenylpropanoid biosynthesis and flavonoid metabolism pathway by increasing the accumulation of cinnamaldehyde, coniferyl aldehyde, naringenin, taxifolin, quercetin, and quercitrin in fruit at 12 h after treatment. In addition, terpinen-4-ol treatment also caused the accumulation of total phenolics and lignin by enhancing activities and relative gene expression of key enzymes in the phenylpropanoid metabolism pathway. These results suggest that terpinen-4-ol, as the key component of TTO, is the most important contributor to the effectiveness of TTO in improving disease resistance of strawberry fruit through activating the phenylpropanoid metabolism pathway.

Molecular sensitization patterns in birch pollen-sensitized Korean children according to the presence of oral allergy syndrome.

The profiles of sensitization based on component-resolved diagnosis (CRD) differ from region to region in populations sensitized to birch pollen. We investigated the endotypes of birch pollen-sensitized Korean children with allergic diseases using CRD and distinguished the endotypes of oral allergy syndrome (OAS) among them.Thirty-one birch pollen-sensitized children with allergic diseases were enrolled. Specific immunoglobulin E (IgE) to birch pollen and fruit including apple, peach, and kiwi were evaluated via skin prick tests and ImmunoCAP in all subjects. Sensitization profiles based on CRD were evaluated with the Immuno-solid-phase Allergen Chip for birch pollen-sensitization using birch pollen components (Bet v 1, Bet v 2, and Bet v 4), and for OAS using the allergen families pathogenesis-related class 10 proteins (PR-10), lipid transfer proteins, and profilin.All patients (n = 13) with OAS were sensitive to Bet v 1. However, 61% (11/18) of patients without OAS were sensitized to Bet v 1. The level of specific IgE to Bet v 1 was higher in patients with OAS than in those without OAS. All birch pollen-sensitized Korean children with OAS were sensitized to PR-10, and 69% (9/13) of them were mono-sensitized to PR-10. Among patients without OAS, 33% (6/18) were not sensitized to any of the allergen families.Birch pollen-sensitized Korean children with allergic diseases showed unique patterns of sensitization to Bet v 1, Bet v 2, and Bet v 4, and the sensitization profiles based on CRD were totally different according to the presence of OAS.

Frequency and clinical features of pollen-food syndrome in children.

BACKGROUND: Pollen-food syndrome (PFS) is an allergic reaction to fresh fruits, vegetables and/or nuts that can occur in patients who are allergic to pollen. The prevalence of PFS in children is not clearly known. OBJECTIVE: The objective of this study was to determine the frequency and clinical features of PFS in pediatric patients with pollen-induced allergic rhinitis (AR). METHOD: This study was conducted in the pediatric allergy outpatient clinic of our hospital. Pollen-induced seasonal AR patients who were evaluated for any symptoms appearing after consuming any fresh fruits and vegetables. RESULTS: Six hundred and seventy-two pollen-sensitized patients were included in this study. The symptoms related to PFS were reported in 22 (3.3%) patients. The median age of the patients was 12.3 years and 59% (n=13) were female. Peach was the most common culprit (22%). There were isolated oropharyngeal symptoms in 20 (91%) patients and anaphylaxis in two (9%) patients with the suspected food. The multiple logistic regression analysis revealed that female gender, history of atopic dermatitis and allergic diseases in the family were the potential risk factors for PFS [Odds ratio 95%CI: 3.367 (1.344-8.435), 5.120 (1.935-13.550), 3.046 (1.239-7.492), respectively]. CONCLUSION: PFS can be seen in children who are followed up for pollen-induced AR. The symptoms of PFS are usually mild and transient. However, comprehensive evaluation of patients is important since serious systemic reactions such as anaphylaxis can also be observed.

Pollen food allergy syndrome to tomato in mountain cedar pollen hypersensitivity.

BACKGROUND: Mountain cedar pollen is recognized as a major cause of seasonal hypersensitivity in the US. We describe here that a subgroup of these patients also suffer from pollen food allergy syndrome (PFAS). OBJECTIVE: We performed this study to determine the frequency of PFAS among patients with mountain cedar hypersensitivity. METHODS: We performed mail-out/telephone surveys of 800 mountain cedar-sensitive patients in Austin, TX. The subjects for this survey were selected by telephone screening, and skin and serologic testing. We performed immunoblot inhibition assay and mass spectrometry (MS) to identify the allergens that cause PFAS. RESULTS: Of the 28 patients with suspected food allergies, 15 had clinical manifestations of PFAS. Eleven of them had positive skin tests to tomato, six to banana, and one to apple. The subjects with PFAS have stronger cutaneous and in vitro reactivity to cedar pollen. The intensities of the tomato and banana reactivity were correlated with the cedar reactivity. The results of the ImmunoCAP inhibition experiments demonstrated a strong cross-reactivity between IgE antibodies to cedar pollen and fruits. This suggested that their primary sensitization was to cedar pollen, since absorption with cedar pollen extract strongly inhibited reactivity to each of the fruits, while the absorption with tomato extract did not significantly inhibit IgE binding to cedar extract. We determined that polygalacturonase 2 A (PG2 A) in tomato is the cause of PFAS. CONCLUSION: This is the first report of a PFAS in patients with mountain cedar pollinosis. Sensitivity to tomato, banana, and apple should be considered in cedar-sensitive patients.

Depression of Fungal Polygalacturonase Activity in Solanum lycopersicum Contributes to Antagonistic Yeast-Mediated Fruit Immunity to Botrytis.

The acquisition of susceptibility to necrotrophy over the course of ripening is one of the critical factors limiting shelf life. In this study, phytopathology and molecular biology were employed to explore the roles of pectinase in fruit susceptibility and ripening. Solanum lycopersicum fruit softened dramatically from entirely green to 50% red, which was accompanied by a continuously high expressed SlPG2 gene. The necrotrophic fungus Botrytis cinerea further activated the expression of SlPGs and SlPMEs to accelerate cell wall disassembly, while most of the polygalacturonase inhibitor proteins encoding genes expression were postponed in ripe fruit following the pathogen attack. Pectin induced the antagonistic yeast to secrete pectinolytic enzymes to increase fruit resistance against gray mold. The activities of pathogenic pectinase of B. cinerea were correspondingly depressed in the pectin-inducible yeast enzyme elicited ripe fruit. These data suggest that pectinase is a molecular target for regulation of disease resistance during fruit ripening.

Detection of profilin in SPT extracts that are supposed to contain it.

INTRODUCTION AND OBJECTIVES: Profilin is a panallergen contained in pollen, plant foods and latex. Although cross-reactivity is expected while performing skin prick tests (SPT) with allergens that contain profilin, this is not always noticed. The purpose of this study was to detect if profilin is contained in the commercial SPT extracts of pollen and plant foods which, in their fresh form, contain determined epitopes of profilin. MATERIAL AND METHODS: Commercial SPT extracts of different pharmaceuticals were analyzed using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The study included purified palm date profilin, peach (whole, pulp and peel extracts), hazelnut, Olea europea, Parietaria judaica and Phleum pratense. RESULTS: Profilin was detected in all, but peach extracts; it was neither contained in the whole peach extract nor in the ones of peel or pulp. CONCLUSION: The only accurate way to detect sensitization to profilin, while performing SPT, is the use of purified profilin extract. Even if a plant food or pollen contain an identified molecule of profilin, the relevant SPT commercial extract may not.

Food-dependent, exercise-induced anaphylaxis in a patient allergic to peach.

Determining the single factor that triggered anaphylactic shock can be challenging. We present an interesting case of a 25-year-old female patient with recurrent anaphylactic reactions developing after eating various foods, particularly in presence of co-factors of allergic reactions. Symptoms occurred after consumption of various kinds of foods - peach, pancakes with cottage cheese and fruit, a meal from a Chinese restaurant - all eaten on other occasions without symptoms. During diagnosis, skin prick tests were negative for all tested allergen extracts (both inhalatory and food) from Allergopharma. Prick by prick tests were positive for the peach - wheal diameter - 6 mm, nectarine - 4 mm (histamine 4 mm, negative control 0 mm). Increased levels of asIgE were found for allergens of peach (0.55 kU/L).Open challenge test with one mid-size peach combined with the physical exercise challenge test was positive. ImmunoCAP ISAC test indicated increased levels of IgE specific for the lipid transfer protein (LTP) for walnut (nJug r 3), peach (Pru p 3), wheat (rTri a 14) and plane tree (rPla a 3). The patient was diagnosed with food-dependent, exercise-induced anaphylaxis associated with an allergy to lipid transport proteins (LTPs).

Effect of the Strawberry Genotype, Cultivation and Processing on the Fra a 1 Allergen Content.

Birch pollen allergic patients show cross-reactivity to vegetables and fruits, including strawberries (Fragaria × ananassa). The objective of this study was to quantify the level of the Fra a 1 protein, a Bet v 1-homologous protein in strawberry fruits by a newly developed ELISA, and determine the effect of genotype, cultivation and food processing on the allergen amount. An indirect competitive ELISA using a specific polyclonal anti-Fra a 1.02 antibody was established and revealed high variability in Fra a 1 levels within 20 different genotypes ranging from 0.67 to 3.97 µg/g fresh weight. Mature fruits of red-, white- and yellow-fruited strawberry cultivars showed similar Fra a 1 concentrations. Compared to fresh strawberries, oven and solar-dried fruits contained slightly lower levels due to thermal treatment during processing. SDS-PAGE and Western blot analysis demonstrated degradation of recombinant Fra a 1.02 after prolonged (>10 min) thermal treatment at 99 °C. In conclusion, the genotype strongly determined the Fra a 1 quantity in strawberries and the color of the mature fruits does not relate to the amount of the PR10-protein. Cultivation conditions (organic and conventional farming) do not affect the Fra a 1 level, and seasonal effects were minor.

Distinguishing allergens from non-allergenic homologues using Physical-Chemical Property (PCP) motifs.

Quantitative guidelines to distinguish allergenic proteins from related, but non-allergenic ones are urgently needed for regulatory agencies, biotech companies and physicians. In a previous study, we found that allergenic proteins populate a relatively small number of protein families, as characterized by the Pfam database. However, these families also contain non-allergenic proteins, meaning that allergenic determinants must lie within more discrete regions of the sequence. Thus, new methods are needed to discriminate allergenic proteins within those families. Physical-Chemical Properties (PCP)-motifs specific for allergens within a Pfam class were determined for 17 highly populated protein domains. A novel scoring method based on PCP-motifs that characterize known allergenic proteins within these families was developed, and validated for those domains. The motif scores distinguished sequences of allergens from a large selection of 80,000 randomly selected non-allergenic sequences. The motif scores for the birch pollen allergen (Bet v 1) family, which also contains related fruit and nut allergens, correlated better than global sequence similarities with clinically observed cross-reactivities among those allergens. Further, we demonstrated that the average scores of allergen specific motifs for allergenic profilins are significantly different from the scores of non-allergenic profilins. Several of the selective motifs coincide with experimentally determined IgE epitopes of allergenic profilins. The motifs also discriminated allergenic pectate lyases, including Jun a 1 from mountain cedar pollen, from similar proteins in the human microbiome, which can be assumed to be non-allergens. The latter lacked key motifs characteristic of the known allergens, some of which correlate with known IgE binding sites.

[A CASE OF A 7-YEAR-OLD GIRL WITH ANAPHYLAXIS CAUSED BY PECTIN IN ALBEDO OF CITRUS UNSHIU BUT NOT BY THE FRUIT ITSELF].

Pectin is used in several foods as an additive and a thickner. But some cases of anaphylaxis have been reported. Most of these are induced by occasional exposures; however, no cases of anaphylaxis after eating a Citrus unshiu, the albedo of which is rich in pectin, have been reported.A 7-year-old girl developed barking cough and pruritus approximately two hours after eating a frozen Citrus unshiu. She had a history of anaphylaxis induced by consuming cashew nuts. Skin testing and basophil activation tests were performed using a commercially available pectin product. Both tests were positive. In an oral food challenge test, she felt abdominal pain and nausea only after eating fruit, along with the albedo, of Citrus unshiu. We concluded that this case was induced by pectin present in the albedo of Citrus unshiu, but not by the fruit itself. We should consider that patients with cashew nut allergies have a possibility of pectin allergies as well, and that pectin in the albedo of Citrus unshiu may induce anaphylaxis.

Comparative analysis of allergen genes and pro-inflammatory factors in pollen and fruit of apple varieties.

Allergy to freshly consumed apple fruits is often associated to pollinosis and manifested as oral allergy syndrome (OAS). The allergenic properties of apple varieties differ greatly, spanning from low allergenic to high allergenic varieties. The knowledge of the genetic determinants for allergenicity has been of great interest in scientific community for several years, but the molecular mechanisms involved are still little understood. Here, factors putatively involved in allergenicity were investigated at biochemical and molecular level in pollen and in fruits of apple varieties differing in their allergenic potential. Among putative sensitizing factors, transglutaminase (TGase) and phospholipase A2 (PLA2) were considered together with reactive oxygen species (ROS) and known apple allergen genes, with particular attention devoted to the Mal d 1 gene family, the most important one in sensitization. We found that the expression of some allergen genes and the activities of TGase, PLA2 and ROS producing enzyme are lower in the hypo-allergenic variety 'Durello di Forlì' in comparison with the high-allergenic genotypes 'Gala' and 'Florina'. These results highlight correlations among allergen expressions, enzymatic activities and apple cultivars; these data underline the possibility that some of them could be used in the future as markers for allergenicity.

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.

Gibberellin-regulated protein (GRP) is a new allergen in peach allergy, with an amino acid sequence very well conserved through several botanical species. We investigated the allergenicity of GRP in fruit allergies other than peaches and identified the clinical characteristics of fruit allergy patients with GRP sensitization. One hundred consecutive Japanese patients with fruit allergies were enrolled in the present study. To identify the features of GRP sensitization, we selected patients with negative ImmunoCAP results for Bet v 1 homologs and profilin, which are marker allergens for pollen-food allergy syndrome (PFAS), or lipid transfer protein. These patients underwent specific immunoglobulin E measurements by enzyme-linked immunosorbent assay (ELISA) and skin prick tests (SPT) using purified nPru p 7. Twenty of 100 consecutive patients with fruit allergies had negative ImmunoCAP results for Bet v 1 homologs and profilin. Thirteen (65.0%) of the 20 patients had positive ELISA and/or SPT results using nPru p 7, whereas one of the 20 patients had positive ImmunoCAP results for Pru p 3. In 13 nPru p 7-sensitized patients, the causative foods were peaches (92.3%), apricots (61.5%), oranges (46.2%) and apples (30.8%). Ten patients (76.9%) had multiple causative fruits. Frequent symptoms included facial edema (92.3%) and laryngeal tightness (66.7%). In eight patients (61.5%), exercise or aspirin intake enhanced the allergic reaction onset as cofactors. The prevalence of GRP sensitization was high in Japanese fruit allergy patients except for PFAS patients. In conclusion, GRP-sensitized patients may have allergies to multiple fruits and may show peculiar characteristics such as facial swelling and cofactor dependence.

Bariatric Surgery: A Novel Risk Factor for Food Allergy?

In this case report, we describe a birch pollen-allergic patient in whom a Fobi pouch gastric bypass was associated with the transition from a mild, localized, birch pollen-related oral allergy syndrome to more severe, generalized allergic reactions to peach.