Cristoforo Incorvaia

Allergenic cross-reactivity among peach, apricot, plum, and cherry in patients with oral allergy syndrome: An in vivo and in vitro study

BACKGROUND Oral allergy syndrome in response to fruits and vegetables frequently occurs as clusters of hypersensitivity to members of the same botanical family, for which the immunologic basis lies in a number of common allergens, most of them still unidentified. OBJECTIVE This study was designed to assess the in vivo and in vitro cross-reactivity between fruits of the Prunoideae subfamily (i.e., peach, cherry, apricot, and plum) and to identify their major allergens and the cross-reactivity of the peach extract with grass and birch pollen. METHODS The in vivo study was conducted by skin prick tests and open food challenges with fresh fruits in 23 patients with oral allergy syndrome for peach and positive skin prick test and RAST results for the other Prunoideae. In vitro sodium dodecylsulfate-polyacrylamide gel electrophoresis was followed by immunoblotting and immunoblotting-inhibition. RESULTS A 13 kd component was identified as the only major allergen common to all the Prunoideae, the other major allergens were found at 14 kd in peach and at 30 kd in cherry. Immunoblotting inhibition showed wide cross-reactivity within the Prunoideae, whereas grass and birch pollen partially inhibited the peach blotting. CONCLUSIONS Clinical cross-reactivity to Prunoideae is essentially due to a common 13 kd IgE-binding component, which seems to be the most important major allergen of this subfamily, not shared with grass and birch pollen.

Studies on the relationship between the level of specific IgE antibodies and the clinical expression of allergy: I. Definition of levels distinguishing patients with symptomatic from patients with asymptomatic allergy to common aeroallergens

BACKGROUND The detection of specific IgE antibodies to environmental allergens does not always coincide with a diagnosis of clinically evident allergic disease, because some patients with positive skin and/or in vitro test results have no symptoms related to the allergen or allergens that induced the antibodies. OBJECTIVE In a multicenter study the optimal cutoff values for specific IgE antibody levels and skin test results that could discriminate between patients with symptomatic and those with asymptomatic allergy were determined. METHODS IgE antibodies specific for a panel of common aeroallergens were assayed with the Pharmacia CAP System (Pharmacia, Uppsala, Sweden) in two groups of patients, a group of 267 patients with symptomatic allergy and a group of 232 with asymptomatic allergy--both with positive skin prick test results--and in a group of 243 healthy, nonallergic control subjects. The cutoff values were established by receiver operating characteristic analysis. RESULTS A significantly higher mean specific IgE antibody value was found in patients with symptomatic allergy compared with patients with asymptomatic allergy (p < 0.001) and in patients with symptomatic allergy compared with healthy control subjects (p < 0.001). The optimal CAP System cutoff value between patients with symptomatic and those with asymptomatic allergy was 11.7 kU/L, and when seasonal allergens were compared with perennial allergens, the cutoffs were 10.7 kU/L and 8.4 kU/L, respectively. The optimal cutoff value for the skin prick test was a wheel area of 32 mm2 for seasonal allergens and 31 mm2 for perennial allergens. The skin test had a lower diagnostic value (sum of sensitivity and specificity) than the CAP System. CONCLUSIONS Cutoff values for specific serum IgE antibody levels are likely to be useful in clinical practice to distinguish symptomatic from asymptomatic allergy in patients with positive skin test results.

Clinical role of a lipid transfer protein that acts as a new apple-specific allergen

BACKGROUND Allergy to apple is commonly associated with birch pollinosis because the two share homologous allergens. However, some patients have apple allergy but no birch pollinosis, suggesting that there are allergens that do not cross-react with birch. OBJECTIVE The aim of the study was to evaluate the IgE reactivity pattern to an apple extract in subjects with allergic reactions to apple, with and without birch hay fever. METHODS Forty-three patients with oral allergy syndrome for apple and positive open food challenge, skin prick test, and serum specific IgE antibodies to apple were admitted to the study. Thirty-two had birch pollinosis (documented by specific IgE for birch) and 11 were not allergic to birch. The IgE reactivity pattern to apple extract was identified by SDS-PAGE and immunoblotting. The consistent allergen, a 9-kd protein, was then purified by HPLC and characterized by periodic acid-Schiff staining, isoelectric point, and N-terminal amino acid sequencing. RESULTS The sera from 28% of patients allergic to apple with birch pollinosis, but from all patients allergic only to apple, recognized the 9-kd protein. This protein has an isoelectric point of 7.5 and is not glycosylated. Determination of its partial amino acid sequence showed that it belongs to the family of lipid transfer proteins, which act as major allergens in Prunoideae fruits. CONCLUSIONS These results indicate that a lipid transfer protein is an important allergen in patients allergic to apple but not to birch pollen. The prevalent IgE reactivity to this allergen in subjects with no birch pollinosis and the physicochemical characteristics of this protein suggest that sensitization may occur through the oral route.

Sensitization to the major allergen of Brazil nut is correlated with the clinical expression of allergy

BACKGROUND Only a few studies have investigated the clinical role of food allergens, especially the relationship between sensitization to a given allergen and occurrence of adverse reactions when eating the relevant food item. OBJECTIVE This study evaluated the clinical role of the allergens of Brazil nut by comparing the patterns of IgE binding in sera from 11 patients with anaphylaxis after eating Brazil nuts with those from 10 subjects with no symptoms to this food item. Both groups had specific IgE to Brazil nut. METHODS Allergens in the in-house extract of Brazil nut were identified by SDS-PAGE/immunoblotting, the major allergen was purified by HPLC, and its N-terminal sequence was determined by a protein sequencer. RESULTS SDS-PAGE/immunoblotting detected a number of allergenic components with molecular weights ranging from 4 to 58 kd. All sera from symptomatic patients recognized a 9-kd allergen corresponding (as established by amino acid sequencing) to a 2S albumin already described as a major allergen of Brazil nut, whereas the other allergens each bound IgE from less than 50% of sera. No sera from asymptomatic subjects showed IgE binding to the 9-kd allergen, but they did recognize components from 25 to 58 kd, which are minor allergens. CONCLUSIONS These findings indicate that the allergen underlying clinical reactions to Brazil nut is a 2S albumin of 9 kd and that in vitro reactivity to this allergen identifies subjects who react in vivo to ingestion of this food.

Safety of sublingual-swallow immunotherapy in children aged 3 to 7 years

BACKGROUND The minimum age to start specific immunotherapy with inhalant allergens in children has not been clearly established, and position papers discourage its use in children younger than 5 years. OBJECTIVE To assess the safety of high-dose sublingual-swallow immunotherapy (SLIT) in a group of children younger than 5 years. METHODS Sixty-five children (51 boys and 14 girls; age range, 38-80 months; mean +/- SD age, 60 +/- 10 years; median age, 60 months) were included in this observational study. They were treated with SLIT with a build-up phase of 11 days, culminating in a top dose of 300 IR (index of reactivity) and a maintenance phase of 300 IR 3 times a week. The allergens used were house dust mites in 42 patients, grass pollen in 11 patients, olive pollen in 5 patients, Parietaria pollen in 4 patients, and cypress pollen in 3 patients. All adverse reactions and changes in the treatment schedule were compared in 2 subgroups: children 38 to 60 months old and children 61. to 80 months old. RESULTS The average cumulative dose of SLIT was 36,900 IR. Adverse reactions were observed in 11 children, none of them severe enough to require discontinuation of immunotherapy. Six reactions occurred in the 60 months or younger age group and 7 in the older than 60 months age group, with no differences between these 2 groups. CONCLUSION High-dose immunotherapy in children younger than 5 years does not cause more adverse reactions than in children aged 5 to 7 years. There is no reason to forbear studies on safety and efficacy of these preparations in young children.

Evidence for a lipid transfer protein as the major allergen of apricot

BACKGROUND Apricots are widely grown in Europe, and allergic reactions are becoming more common, especially oral allergy syndrome. Apricot belongs to the botanical subfamily of Prunoideae, which includes peach, the major allergen of which was identified as a 9-kd protein, a lipid transfer protein (LTP). OBJECTIVE The aim of the study was to evaluate the IgE reactivity pattern to an apricot extract in subjects with allergic reactions to apricot, as demonstrated by a positive oral challenge response. METHODS Thirty patients were investigated. All the patients displayed oral allergy syndrome (2 with systemic reactions) to apricot, with positive open food challenge responses, skin prick test responses, and serum-specific IgE antibodies to apricot. The IgE reactivity pattern to apricot extract was identified by using SDS-PAGE and immunoblotting. The major allergen, a 9-kd protein, was then purified by HPLC and characterized by periodic acid-Schiff stain, isoelectric point determination, and N-terminal amino acid sequencing. RESULTS The sera from all patients allergic to apricot recognized the 9-kd protein, whereas none of the other allergens, with molecular weights from 15 to 80 kd, acted as a major allergen. The 9-kd allergen has an isoelectric point of 8.7 and is not glycosylated. Determination of the N-terminal 34 amino acid sequence showed that it belongs to the LTP family, with a 94% homology with the LTP from peach. IgE blotting of the apricot extract was completely inhibited by the 9-kd purified LTP from peach. CONCLUSIONS The major allergen of apricot is an LTP, which is highly cross-reactive with the LTP from peach.

Dose dependence of immunological response to sublingual immunotherapy

Background:  Sublingual‐swallow immunotherapy (SLIT) is an accepted treatment for allergic rhinitis but its optimal dosage is scantly investigated. We studied the dose dependence of clinical efficacy and immunological response to SLIT by administering two different dosages of the same allergen in rhinitic children monosensitized to grass pollen.

Birch-Apple Syndrome Treated with Birch Pollen Immunotherapy

Background: The most common pollen-fruit cross-reaction is the birch-apple syndrome. Allergen immunotherapy (IT) is clearly effective for birch allergy, but its efficacy on apple allergy is controversial. We performed a randomized study on patients with birch-apple syndrome to evaluate the outcome of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT). Methods: Forty patients underwent IT with a birch extract (Staloral; Stallergenes, Antony, France), 20 by SCIT and 20 by SLIT. After 1 year of treatment, 15 patients (8 for SCIT and 7 for SLIT) accepted to undergo an oral apple challenge. Measurements of specific IgE to Bet v 1 and Mal d 1 and related allergens Api g 1 and Dau c 1 were obtained in 10 patients, at baseline and after IT. Results: Two of 8 SCIT-treated patients (25%) and 1 of 7 SLIT-treated patients (14.2%) developed complete tolerance to apple. In the remaining patients, an increase in the provocative dose was found in 3 of the SCIT-treated (37.5%) and 2 of the SLIT-treated patients (28.6%). Changes in the levels of specific IgE to Mal d 1 were unrelated to clinical results. Conclusions: These findings suggest that different doses of birch extract may be needed in different patients to improve the associated apple allergy and that a finer diagnostic work-up in selecting patients with birch-apple syndrome who are candidates to respond to birch pollen IT also concerning apple allergy is required.

Patient's compliance with allergen immunotherapy.

Background Allergen immunotherapy (IT) is an effective treatment of respiratory allergy, but requires strict rules of performance. This makes compliance particularly relevant, but thus far only a few studies have investigated this issue. Methods We reviewed all the available articles on compliance and adherence with IT in its different forms of administration, ie, subcutaneous (SCIT), sublingual (SLIT), and local nasal (LNIT). Results Early studies, when only SCIT was available, reported a low compliance, ranging from 45% to 60%, but the demanding schedules used, with very frequent injections, accounted for this outcome, as shown by patients’ recognition of inconvenience as the major cause of noncompliance. The most recent studies reported a good compliance, estimated in 75% to 90%, to both SCIT and SLIT, inconvenience remaining the major cause of noncompliance, followed by cost of the treatment. The only study addressing LNIT found a very poor compliance (27%), the major cause being the side effects, with repeated nasal reactions to the allergen extract. Conclusions Adequate education of patients and optimization of administration schedules, with fine balancing between dose effectiveness and cost, are the factors most likely to achieve further improvement of compliance with IT.

Types of sensitization to aeroallergens: definitions, prevalences and impact on the diagnosis and treatment of allergic respiratory disease

The type of allergic sensitization is of central importance in the diagnosis and treatment of respiratory allergic diseases. At least 10% of the general population (and more than 50% of patients consulting for respiratory allergies) are polysensitized. Here, we review the recent literature on (i) the concepts of polysensitization, paucisensitization, co-sensitization, co-recognition, cross-reactivity, cross-sensitization, and polyallergy, (ii) the prevalence of polysensitization and (iii) the relationships between sensitization status, disease severity and treatment strategies. In molecular terms, clinical polysensitization can be divided into cross-sensitization (also known as cross-reactivity, in which the same IgE molecule binds to several allergens with common structural features) and co-sensitization (the simultaneous presence of different IgEs binding to allergens that may not necessarily have common structural features). There is a strong overall association between sensitization in skin prick tests and total IgE values but there is debate as to whether IgE thresholds are useful guides to the presence or absence of clinical symptoms in individual cases. Molecular information from component-resolved techniques appears to be of value for diagnosis and treatment decisions. Polysensitization develops over time and is a risk factor for respiratory allergy (being associated with disease severity) and therefore has clinical relevance for treatment decisions. The subterm polysensitization has been defined as polysensitization to between two and four allergens. Polyallergy is defined as clinically confirmed allergy to two or more allergens. Single-allergen grass pollen allergen immunotherapy (AIT) is safe and effective in polysensitized patients, whereas multi-allergen AIT requires more supporting evidence. Given that AIT may be more efficacious in moderate-to-severe disease than in mild disease, polysensitization could be an indication for this type of treatment. There is a need for flowcharts or decision trees for choosing the allergens for AIT in polysensitized patients and polyallergic patients.