Diagnosis and Management of Pollen Food Allergy Syndrome to Nuts.

Oral allergy syndrome or pollen food allergy syndrome (PFAS) represents a common clinical conundrum when the reported trigger food is a tree nut (usually almond or hazelnut) or peanut. The PFAS may give rise to uncertainty about the potential severity of the future reactions, indications for prescribing epinephrine, and the extent of the necessary dietary avoidance. As a food allergy, secondary to cross-reactivity with airborne pollen, PFAS usually manifests toward the end of the first decade of life as contact urticaria of the oropharyngeal mucous membranes. Molecular allergology facilitates diagnosis and risk stratification by establishing the profile of sensitization. Exclusive sensitization to pathogenesis-related proteins family 10 (PR10) and profilins indicates that signs and symptoms are due to PFAS, whereas sensitization to seed storage proteins with or without sensitization to PR10 and profilins may indicate a more severe primary nut allergy phenotype. Management relies on avoidance of the specific nut trigger, advice on the likelihood of more severe local or systemic symptoms, and treatment of reactions according to the severity. Future studies are needed to better delineate the risk of systemic reactions in individuals with nut PFAS and to establish the role of food or pollen allergen immunotherapy for the prevention or moderation of this condition.

The Role of Defensins as Pollen and Food Allergens.

PURPOSE OF REVIEW: Defensin-polyproline-linked proteins are relevant allergens in Asteraceae pollen. Depending on their prevalence and amount in the pollen source, they are potent allergens, as shown for the major mugwort pollen allergen Art v 1. Only a few allergenic defensins have been identified in plant foods, such as peanut and celery. This review provides an overview of structural and immunological features, IgE cross-reactivity, and diagnostic and therapeutic options regarding allergenic defensins. RECENT FINDINGS: We present and critically review the allergenic relevance of pollen and food defensins. The recently identified Api g 7 from celeriac and other allergens potentially involved in Artemisia pollen-related food allergies are discussed and related to clinical severity and allergen stability. To specify Artemisia pollen-related food allergies, we propose the term "defensin-related food allergies" to account for defensin-polyproline-linked protein-associated food syndromes. There is increasing evidence that defensins are the causative molecules in several mugwort pollen-associated food allergies. A small number of studies have shown IgE cross-reactivity of Art v 1 with celeriac, horse chestnut, mango, and sunflower seed defensins, while the underlying allergenic molecule remains unknown in other mugwort pollen-associated food allergies. As these food allergies can cause severe allergic reactions, identification of allergenic food defensins and further clinical studies with larger patient cohorts are required. This will allow molecule-based allergy diagnosis and a better understanding of defensin-related food allergies to raise awareness of potentially severe food allergies due to primary sensitization to Artemisia pollen.

BSACI guideline for the diagnosis and management of pollen food syndrome in the UK.

Pollen food syndrome (PFS) is a highly prevalent food allergy affecting pollen-sensitized children and adults. Sufferers experience allergic symptoms when consuming raw plant foods, due to the homology between the pollen allergens and unstable proteins in these foods. The triggers involved can vary depending on the pollen sensitization, which in turn is affected by geographical location. The British Society of Allergy and Clinical Immunology (BSACI) Standards of Care Committee (SOCC) identified a need to develop a guideline for the diagnosis and management of PFS in the United Kingdom (UK). Guidelines produced by the BSACI use either the GRADE or SIGN methodology; due to a lack of high-quality evidence these recommendations were formulated using the SIGN guidelines, which is acknowledged to be less robust than the GRADE approach. The correct diagnosis of PFS ensures the avoidance of a misdiagnosis of a primary peanut or tree nut allergy or confusion with another plant food allergy to non-specific lipid transfer proteins. The characteristic foods involved, and rapid-onset oropharyngeal symptoms, mean PFS can often be diagnosed from the clinical history alone. However, reactions involving tree nuts, peanuts and soya milk or severe/atypical reactions to fruits and vegetables may require additional diagnostic tests. Management is through the exclusion of known trigger foods, which may appear to be simple, but is highly problematic if coupled with a pre-existing food allergy or for individuals following a vegetarian/vegan diet. Immunotherapy to pollens is not an effective treatment for PFS, and although oral or sublingual immunotherapy to foods seems more promising, large, controlled studies are needed. The typically mild symptoms of PFS can lead to an erroneous perception that this condition is always easily managed, but severe reactions can occur, and anxiety about the onset of symptoms to new foods can have a profound effect on quality of life.

Real-life evaluation of molecular multiplex IgE test methods in the diagnosis of pollen associated food allergy.

BACKGROUND: Diagnosis of food allergies is challenging, as combining information from specific IgE (sIgE)-sensitization pattern and skin prick tests (SPTs) with clinical history is necessary for a personalized management of allergic patients. The aim of this study was to compare two molecular tests, the ImmunoCAP ISAC (ISAC) and the Allergy Explorer, version 2 (ALEX2 ) in the context of pollen food syndrome (PFS) diagnosis in a real-life scenario, to assess the benefit of multiplex testing in PFS patients. METHODS: Diagnosis of food allergy was performed in 53 patients. Allergen-sIgE concentrations were measured with ISAC and ALEX2 . Results for sIgE were statistically compared with each other, with SPT results and with clinical presentation of the patients. RESULTS: Using ISAC as reference test for sIgE measurements, the average sensitivity of ALEX2 for PR-10 allergens was 83.2% and the average specificity 88.0%. If only low sIgE concentrations were included, the sensitivity was 60.8% and the specificity 91.1%. Apple and hazelnut sensitizations were confirmed in most patients by concordance of sIgE and SPT results. Significant correlations were shown between clinical symptoms and Mal d 1- and Gly m 4-sIgE levels measured by both tests and for Cor a 1-sIgE levels measured by ALEX2 . In eight patients, profilin related symptoms were supported by Hev b 8-sensitization. CONCLUSION: Multiplex testing is beneficial to understand patient-specific individual sensitization profiles and to providing personalized management recommendations. In the future, custom-designed test kits might enable reducing costs of multiplex testing for specific patient groups without compromising the diagnostic value.

[Pollen-food syndrom. A rewiev with a twist]. / Síndrome polen-alimento. Revisión con un toque.

Pollen-food syndrome (PFS) is characterized by allergic sensitization to proteins of pollens of grasses, weeds, and trees, which produce a type I hypersensitivity reaction that is associated with the intake of plant-derived foods that are usually in raw form. The most frequently-associated protein families are: profilins, PR-10, and ns LTP; however, others such as thaumatins, isoflavones, reductases, and B1,2 glucanases have been documented. The prototype syndrome is birch-fruit-vegetables, and of these, the most common is birch-apple due to the fact that more than 70 % of patients who are sensitized to birch present symptoms associated with the intake of plant-derived foods. The symptoms are restricted to the oral cavity; however, some patients may present systemic symptoms, including anaphylaxis, so it is important to identify the type of protein that is involved since the type of reaction that the patient may present depends on that. In spite of everything, it is considered an entity that may be under diagnosed due to its complex diagnosis and treatment, since the procedure, in most cases, is an elimination diet, because treatment with immunotherapy is not yet available. The purpose of this review is to describe the pathophysiology, as well as the most common pollen-food syndromes.

El síndrome polen-alimento (SPA) se caracteriza por la sensibilización alérgica a proteínas de pólenes de pastos, malezas y árboles, que producen una reacción de hipersensibilidad de tipo I, asociada a la ingesta de alimentos derivados de plantas, usualmente en forma cruda. Las familias de proteínas que más frecuentemente están asociadas son las profilinas, las PR-10 y las ns LTP; sin embargo, se ha documentado otras, como las taumatinas, isoflavonas reductasas y las B1,2 gluconasas. El síndrome prototipo es el abedul-frutas-vegetales, y de ellos el más común es el abedul-manzana, debido a que más de 70 % de los pacientes sensibilizados al abedul presentan síntomas asociados a la ingesta de alimentos derivados de plantas. Los síntomas están restringidos a la cavidad oral; sin embargo, algunos pacientes pueden presentar síntomas sistémicos, incluso anafilaxia, por lo que es importante identificar el tipo de proteína implicada, ya que de eso depende el tipo de reacción que puede presentar el paciente. Pese a todo, se considera una entidad que puede estar subdiagnosticada debido a su valoración y tratamiento complejos, debido a que el procedimiento en la mayor parte de los casos es dieta de eliminación, ya que aún no está disponible el tratamiento con inmunoterapia. El objetivo de esta revisión es describir la fisiopatología, así como los síndromes polen-alimento más comunes.

Hazelnut Allergy.

Background and Objectives: Hazelnuts are frequently involved in IgE-mediated reactions and represent the main culprit of nut allergy in Europe. The clinical presentation varies from mild symptoms limited to the oropharynx [oral allergy syndrome (OAS)], due to the cross-reaction with homologues in pollen allergens and more severe events caused by the primary sensitization to highly stable molecules contained in hazelnuts. The aim of this review is to summarize the most relevant concepts in the field of hazelnut allergy and to provide a practical approach useful in the clinical practice Materials and Methods: References were identified by PubMed searches dating from January 2000 up to November 2020 using the search terms: "component resolved diagnosis" and "Hazelnut allergy. Results: The storage proteins Cor a 9 and Cor a 14 resulted highly specific for primary hazelnut allergy and strongly associated with severe reactions, while the cross reactive Cor a 1, an homolog of the birch Bet v1, were related to OAS. Any cut-off has shown a specificity and sensitivity pattern as high as to replace the oral food challenge (OFC), which still remains the gold standard in the diagnosis of hazelnut allergy. To date there is still no definitive treatment. Hazelnut free-diet and treatment of symptoms with emergency management, including the prescription of auto-injective epinephrine, still represent the main approach. Oral allergen immunotherapy (AIT) appears a promising therapeutic strategy and the definition of individual clinical threshold would be useful for sensitized individuals, caregivers, and physicians to reduce social limitation, anxiety, and better manage food allergy. Conclusions: An accurate diagnostic work-up including clinical history, in vivo and in vitro test including component resolved diagnosis and OFC are essential to confirm the diagnosis, to assess the risk of a severe reaction, and to prescribe an adequate diet and treatment.

Sensitization to Gibberellin-Regulated Protein (Peamaclein) Among Italian Cypress Pollen-Sensitized Patients.

BACKGROUND AND OBJECTIVES: Peach gibberellin-regulated protein (peamaclein) has recently emerged as a relevant food allergen in cypress pollen-hypersensitive patients. Objective: We investigated monosensitization to peamaclein among Italian cypress pollen-allergic patients. MATERIAL AND METHODS: A total of 835 cypress pollen-hypersensitive patients from 28 Italian allergy centers underwent a thorough work-up to determine food-allergic reactions and performed skin prick testing with a commercial peach extract containing peamaclein. IgE to rPru p 3 was measured in peach reactors, and those with negative results were enrolled as potentially monosensitized to peamaclein. IgE reactivity to rPru p 7 was evaluated using immunoblot and an experimental ImmunoCAP with rPru p 7. RESULTS: Skin prick tests were positive to peach in 163 patients (19.5%); however, 127 (77.9%) were excluded because they reacted to Pru p 3. Twenty-four patients (14.7%) corresponding to 2.8% of the entire study population) were considered potentially monosensitized to peamaclein. No geographic preference was observed. Seventeen of the 24 patients (70.8%) had a history of food allergy, mainly to peach (n=15). Additional offending foods included other Rosaceae, citrus fruits, fig, melon, tree nuts, and kiwi. On peach immunoblot, only 3 of 18 putative peamaclein-allergic patients reacted to a band at about 7 kDa; an additional 4 patients reacted at about 50-60 kDa. Ten of 18 patients (56%) had a positive result for Pru p 7 on ImmunoCAP. CONCLUSION: Allergy and sensitization to peamaclein seem rare in Italy. Most patients react to peach, although other Rosaceae fruits and several citrus fruits may also be offending foods. Peach and cypress pollen probably also share cross-reacting allergens other than peamaclein.

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.

Comparative structural and thermal stability studies of Cuc m 2.0101, Art v 4.0101 and other allergenic profilins.

Worldwide, more than one-third of the population suffers from allergies. A significant fraction of officially registered allergens originate from the profilin family of proteins. Profilins are small ubiquitous proteins which are found in plants, viruses and various eukaryotes including mammals. Although they are primarily regarded as minor allergens, profilins are important players in immunoglobulin E (IgE) cross-reactivity. However, in some populations profilins are recognized by IgE from at least 50% of patients allergic to a given allergen source. Cuc m 2.0101 is recognized by IgE in more than 80% of muskmelon-allergic patients. The recombinant isoallergen Cuc m 2.0101 was produced in significant quantities and its X-ray crystal structure was determined. In addition, a new Art v 4.0101 (mugwort profilin) structure was determined. The profilins Cuc m 2.0101 and Art v 4.0101 were compared in terms of their structure and thermal stability. Furthermore, structural similarities and IgE cross-reactivity between profilins from different sources are discussed to explain the molecular basis of various clinical syndromes involving this group of allergens. Special emphasis is placed on discussion of profilins' quaternary structures and their relation to biological function, as well as to protein allergenicity. Moreover, a potential impact of protein purification protocols on the structure of profilins is highlighted.

Oral Allergy Syndrome in Birch Pollen-Sensitized Patients from a Korean University Hospital.

BACKGROUND: Oral allergy syndrome (OAS) is a type of allergic reaction that mainly occurs on oral contact with raw fruit, vegetables, or nuts. The most common type of OAS is birch pollen-related food allergy. Although OAS is a common food allergy in adults, only few epidemiologic studies have been reported in Korea. Here we investigate the prevalence and triggers of birch pollen-related food allergy. METHODS: We conducted a retrospective chart review of 1,427 patients who underwent a skin prick test for inhalant allergens at the Asthma and Allergy Clinic in Seoul National University Bundang Hospital from January 2011 to December 2016. RESULTS: Of 1,427 patients, 125 (8.7%) were sensitized to birch pollen. Among them, 20.0% developed OAS, which was the most common food allergy (96.2%). The prevalence of OAS was higher in females, and was 18.2% in birch pollen-sensitized allergic rhinoconjunctivitis patients. Further, 72.0% OAS patients had rhinoconjunctivitis, 20.0% had asthma, and 12.0% had chronic urticaria. Apple (68.0%), peach (56.0%), nuts (36.0%), kiwi (20.0%), persimmon (20.0%), plum (16.0%), and cherry (16.0%) were frequent triggers; however, Chinese yam, kudzu vine, bellflower root, codonopsis, and ginseng were also revealed as triggers. Patients (60.0%) showed OAS with ≥ 3 foods at the same time. Only 3 patients showed mono-sensitivity to birch pollen, while others were multi-sensitized to trees, grasses, weed, or house dust mite allergens. CONCLUSION: OAS was the most common food allergy in birch pollen-sensitized patients. This study revealed the unique triggers of OAS in Korea in addition to well-known triggers.

The concordance between component tests and clinical history in British adults with suspected pollen-food syndrome to peanut and hazelnut.

BACKGROUND: Mild oropharyngeal symptoms to peanut/hazelnut occur in ~30% of patients with pollen-food syndrome (PFS). Component tests are considered a useful adjunct to the diagnosis and may help differentiate PFS from those at a risk of anaphylaxis due to storage protein/lipid transfer protein (LTP) sensitisation. AIMS: To assess concordance between component tests and clinical history in suspected PFS to peanut/hazelnut in a specialist clinic. METHODS: Adult patients were classified into PFS (group 1, n=69) and PFS with mild systemic symptoms (group 2, n=45) based on clinical history. Specific IgE (sIgE) of ≥0.35 kUA/L was considered positive as per manufacturers' recommendation. Kappa (κ) inter-rater agreement was calculated for concordance between clinical classification and test profiles. RESULTS: Group 1 hazelnut: 85% monosensitised to Cor a1, 12% to storage protein/s or LTP and 3% negative to all components. Group 1 peanut: 41% monosensitised to Ara h8, 44% to storage protein/s or ±LTP and 15% negative to all components. Group 2 hazelnut: 67% monosensitised to Cor a1, 16% sensitised to storage protein/s and 17% negative to all components. Group 2 peanut: 19% monosensitised to Ara h8, 62% sensitised to storage protein/s and/or LTP and 19% negative to all components.SIgE to Ara h8 and Cor a1 were greater in group 1 versus group 2: (median (IQR) kUA/L; hazelnut: 12.1 (7.8-25.2) vs 2.4 (0.36-6.3), p<0.001; peanut: 2.4 (0.10-21.1) vs 0.3 (0-3), p<0.01)). CONCLUSION: Concordance between component tests and clinical history for adults with PFS was good for hazelnut (κ=0.63) but poor for peanut (κ=-0.12). Food challenges are warranted in discordant cases for an accurate diagnosis.

Oral Allergy Syndrome in Birch Pollen-Sensitized Patients from a Korean University Hospital

BACKGROUND: Oral allergy syndrome (OAS) is a type of allergic reaction that mainly occurs on oral contact with raw fruit, vegetables, or nuts. The most common type of OAS is birch pollen-related food allergy. Although OAS is a common food allergy in adults, only few epidemiologic studies have been reported in Korea. Here we investigate the prevalence and triggers of birch pollen-related food allergy. METHODS: We conducted a retrospective chart review of 1,427 patients who underwent a skin prick test for inhalant allergens at the Asthma and Allergy Clinic in Seoul National University Bundang Hospital from January 2011 to December 2016. RESULTS: Of 1,427 patients, 125 (8.7%) were sensitized to birch pollen. Among them, 20.0% developed OAS, which was the most common food allergy (96.2%). The prevalence of OAS was higher in females, and was 18.2% in birch pollen-sensitized allergic rhinoconjunctivitis patients. Further, 72.0% OAS patients had rhinoconjunctivitis, 20.0% had asthma, and 12.0% had chronic urticaria. Apple (68.0%), peach (56.0%), nuts (36.0%), kiwi (20.0%), persimmon (20.0%), plum (16.0%), and cherry (16.0%) were frequent triggers; however, Chinese yam, kudzu vine, bellflower root, codonopsis, and ginseng were also revealed as triggers. Patients (60.0%) showed OAS with ≥ 3 foods at the same time. Only 3 patients showed mono-sensitivity to birch pollen, while others were multi-sensitized to trees, grasses, weed, or house dust mite allergens. CONCLUSION: OAS was the most common food allergy in birch pollen-sensitized patients. This study revealed the unique triggers of OAS in Korea in addition to well-known triggers.

Endotypes of pollen-food syndrome in children with seasonal allergic rhinoconjunctivitis: a molecular classification.

BACKGROUND: Pollen-food syndrome (PFS) is heterogeneous with regard to triggers, severity, natural history, comorbidities, and response to treatment. Our study aimed to classify different endotypes of PFS based on IgE sensitization to panallergens. METHODS: We examined 1271 Italian children (age 4-18 years) with seasonal allergic rhinoconjunctivitis (SAR). Foods triggering PFS were acquired by questionnaire. Skin prick tests were performed with commercial pollen extracts. IgE to panallergens Phl p 12 (profilin), Bet v 1 (PR-10), and Pru p 3 (nsLTP) were tested by ImmunoCAP FEIA. An unsupervised hierarchical agglomerative clustering method was applied within PFS population. RESULTS: PFS was observed in 300/1271 children (24%). Cluster analysis identified five PFS endotypes linked to panallergen IgE sensitization: (i) cosensitization to ≥2 panallergens ('multi-panallergen PFS'); (ii-iv) sensitization to either profilin, or nsLTP, or PR-10 ('mono-panallergen PFS'); (v) no sensitization to panallergens ('no-panallergen PFS'). These endotypes showed peculiar characteristics: (i) 'multi-panallergen PFS': severe disease with frequent allergic comorbidities and multiple offending foods; (ii) 'profilin PFS': oral allergy syndrome (OAS) triggered by Cucurbitaceae; (iii) 'LTP PFS': living in Southern Italy, OAS triggered by hazelnut and peanut; (iv) 'PR-10 PFS': OAS triggered by Rosaceae; and (v) 'no-panallergen PFS': mild disease and OAS triggered by kiwifruit. CONCLUSIONS: In a Mediterranean country characterized by multiple pollen exposures, PFS is a complex and frequent complication of childhood SAR, with five distinct endotypes marked by peculiar profiles of IgE sensitization to panallergens. Prospective studies in cohorts of patients with PFS are now required to test whether this novel classification may be useful for diagnostic and therapeutic purposes in the clinical practice.

The prevalence of the oral allergy syndrome and pollen-food syndrome in an atopic paediatric population in south-west Sydney.

AIM: Oral allergy syndrome (OAS) and pollen-food syndrome (PFS) are regarded as uncommon manifestations of paediatric atopic disease. However, little Australian data exist. The aim of this study was to examine the prevalence of OAS in an atopic, paediatric population. METHODS: This cross-sectional study assessed 163 patients aged 4-17 years from the Paediatric Allergy & Immunology Clinic at Campbelltown Hospital, which serves a population base >250,000 with approximately 28% under the age of 18 years. A questionnaire was administered and skin prick tests (SPTs) were performed utilising commercial extracts and fresh and frozen fruit samples. Frozen samples were created by reducing fresh fruit to a semi-solid state and storing at -20 degrees Celsius for up to 6 months. RESULTS: Within the studied population, the prevalence of OAS was 14.7%, PFS 4.9%, PFS in those with allergic rhinitis 6.25% and PFS in those with allergic rhinitis and pollen sensitisation 12.1%. All PFS-implicated fruits were tropical fruits with watermelon the most common. The prevalence of OAS caused by food allergy was 13.6%, implicating peanut most frequently. The most common cause of OAS was immunoglobulin E-mediated food allergy (57.9%). Only frozen samples of watermelon, pineapple and rockmelon produced results consistent with the 'gold standard' of fresh fruit SPT. CONCLUSION: This study suggests the prevalence of OAS and PFS are more common in paediatric populations than previously described, with tropical fruits predominantly implicated in PFS. Further research is required to determine whether frozen fruits are a reliable alternative to fresh fruit in SPT.

Imbalance of serum IL-10 and TGF-ß in patients with pollen food syndrome.

BACKGROUND: Pollen food syndrome is one of the main causes of food allergies in adults. However, the intrinsic immunological mechanisms remain unclear. METHODS: Forty pollinosis sufferers [23 with a food allergy (PSFA) and 17 without a food allergy (PS)] and 17 non-atopic healthy controls were included in this study. The PSFA group was subdivided into an oral allergy syndrome group, a systemic reaction group, and an anaphylactic reaction group according to their symptoms after eating the suspected foods. Serum IL-10 and TGF-ß levels of all participants were determined by ELISA. Clinical characteristics of the patients were also evaluated. RESULTS: There were no significant differences in age, sex, pollen-associated symptoms, duration of respiratory disease, and positive parental history of atopy between the PSFA and PS groups. Compared to healthy controls, serum IL-10 levels of both the PSFA group and PS group were significantly lower (p≤0.01), but TGF ß levels were significantly higher in the PSFA group (35.3±5.6ng/ml vs. 31.2±6.6ng/ml, respectively; p=0.037). Within the PSFA group, IL-10 levels in the anaphylactic reaction subgroup were significantly lower compared to oral allergy syndrome subgroup (1.87±0.47pg/ml vs. 1.40±0.30pg/ml, respectively; p=0.027). More severe food allergy symptoms were associated with lower serum IL-10 levels. In contrast, the highest serum levels of TGF-ß were found in patients from the anaphylactic reaction subgroup. CONCLUSIONS: With the exception of a defect in regulatory cells represented by the reduction of IL-10, other potential immunological mechanisms (e.g., Th17 or IL-23 together with TGF-ß) may be involved in the development of pollen food syndrome.