Allergen Recognition Patterns in Walnut Allergy Are Age Dependent and Correlate with the Severity of Allergic Reactions.

BACKGROUND: Walnut is an important elicitor of food allergy in children and adults with a high rate of severe reactions. Multicenter studies using a common clinical protocol and a comprehensive allergen are lacking. OBJECTIVE: To investigate potential correlations between molecular sensitization patterns and clinical characteristics of walnut-allergic patients. METHODS: A total of 91 walnut-allergic subjects and 24 tolerant controls from Switzerland, Germany, and Spain were included. Walnut allergy was established by food challenge in all but anaphylactic subjects. Specific IgE (sIgE) to walnut extract, rJug r 1 (2S albumin), rJug r 3 (nonspecific lipid transfer protein 1), nJug r 4 (11S globulin), rJug r 5 (PR-10 protein), 2 vicilin fractions, profiling, and cross-reactive carbohydrate determinant was determined by ImmunoCAP. A threshold of 0.10 kUA/L was used for positivity. RESULTS: Sensitivity of sIgE to walnut extract was 87% and increased to 96% for the sum of all walnut components. sIgE to walnut extract and all walnut components, except rJug r 5, was significantly higher in patients younger than 14 years at inclusion. Stratification by age at onset of walnut allergy led to similar results. All patients younger than 14 years had severe reactions, whereas 38% of patients 14 years or older were mild reactors. Severe reactors (n = 70) had higher sIgE levels than did mild reactors (n = 21) to walnut extract (P < .0001), rJug r 1 (P < .0001), nJug r 4 (P = .0003), and both vicilin fractions (P < .0001), but not to Jug r 3 and Jug r 5. CONCLUSIONS: Sensitization to walnut storage proteins is acquired in childhood and correlates with severe reactions. sIgE levels to storage proteins Jug r 1 and Jug r 4 and vicilin fractions, but not to nonspecific lipid transfer protein and PR-10 proteins, correlate with systemic reactions to walnut.

Food allergy in adolescence and adulthood.

In young children, food allergy is usually acquired via the gastrointestinal tract and directed toward egg and milk. Adolescent and adult patients, however, mainly acquire food allergy via primary sensitization to inhalant allergens on the basis of cross-reactivity between proteins in inhalant sources and in food. This type of food allergy is frequently mediated by sensitization to broadly represented allergens, or so-called panallergens. Food allergic reactions in adult patients - similar to those in children - range in severity from very mild and local symptoms, as in contact urticaria of the oral mucosa, to systemic symptoms involving distal organs, to a fatal outcome. Plant foods, such as fruits, nuts, and vegetables, are the most prevalent allergenic foods in this age group.

[Food allergy:definitions, prevalence, diagnosis and therapy].

Food allergy is phenotypically an extremely heterogeneous group of diseases affecting multiple organs, sometimes in an isolated way, sometimes simultaneously, with the severity of reactions ranging from mild and local to full-blown anaphylaxis. Mechanistically, it is defined as a Th2-driven immune disorder in which food-specific IgE antibodies are at the basis of immediate-type adverse reactions. The sites of sensitization and symptoms do not necessarily overlap. Food allergy, which is the theme of this paper, is often confused with other adverse reactions to food of both animmune (e.g., celiac disease) and non-immune (e.g., lactose intolerance) nature. To reliably diagnose food allergy, a careful history (immediate-type reactions) needs to be complemented with demonstration of specific IgE (immune mechanism) and confirmed by an oral challenge. Co-factors such as exercise, medication, and alcohol may help trigger food allergy and further complicate accurate diagnosis. Where food extract-based diagnostic tests are poorly correlated to symptom severity, new generation molecular diagnostics that measure IgE against individual food allergens provide clinicians and patients with more reliable symptom severity risk profiles. Molecular diagnostics also support establishing whether food sensitization originates directly from exposure to food or indirectly (cross-reactivity) from pollen sensitization. Epidemiological surveys have indicated that allergy to peach primarily originates from peach consumption in Europe, whereas in China it is the result of primary sensitization to mugwort pollen, in both cases mediated by an allergen molecule from the same family. Epidemiological surveys give insight into the etiology of food allergy, the size of the problem (prevalence), and the risk factors involved, which together support evidence-based strategies for prevention. Over the past decade, food allergy has increased in the affluent world. Economic growth and urbanization in upcoming economies are likewise expected to lead to increased prevalence of food allergies, sometimes to different foods due to dietary habits. Molecular allergology and biotechnology now offer the possibility to combat the increasing burden of food allergy by developing safe immunotherapies for food allergy, using hypoallergenic mutant recombinant molecules. The first clinical trials to evaluate such approaches are underway. Last but not least, the identification and clinical risk characterization of a more and more complete list of food allergens additionally provides the allergenicity risk assessment of genetically modified foods a firmer basis.

Molecular diagnosis of fruit and vegetable allergy.

PURPOSE OF REVIEW: The purpose of this paper is to review and discuss studies on molecular diagnosis in fruit and vegetable allergy. RECENT FINDINGS: Celeriac, carrot and tomato are the most prevalent allergenic vegetables, whereas fruit allergy is mainly induced by apple, peach and kiwi. Component-resolved molecular diagnosis has been recently applied in two well-defined patient groups with kiwifruit and celeriac allergy, respectively. In kiwifruit allergy Act d 1 and Act d 3 were identified as potential marker allergens for severe symptoms. For celeriac allergy, however, such markers are still missing. In both studies component-resolved molecular diagnosis approach improved in particular sensitivity compared to extract-based diagnostic test assays. SUMMARY: Food and vegetable allergy can be acquired both via a direct sensitization over the gastrointestinal tract and via a primary sensitization to pollen or latex. The diagnosis of fruit and vegetable allergy in birch pollen-sensitized patients should not be excluded on a negative IgE testing to extracts. Bet v 1-related allergens are often under-represented in extracts. Few recombinant allergens derived from fruits and vegetables are nowadays commercially available and facilitate diagnosis of fruit and vegetable allergies.

Birch pollen-related food allergy: clinical aspects and the role of allergen-specific IgE and IgG4 antibodies.

BACKGROUND: Patients with birch pollen allergy often develop allergic reactions to plant foods. OBJECTIVE: To evaluate the prevalence, main symptoms, and triggers of birch pollen-related food allergy and the role of food-specific IgG(4) antibodies in food tolerance. METHODS: Food-induced symptoms were evaluated in 225 individuals with birch pollen allergy by using a standardized questionnaire. IgE and IgG(4) levels specific for the major birch pollen allergen Bet v 1 and birch profilin Bet v 2 and the Bet v 1 homologs in apple (Mal d 1) and hazelnut (Cor a 1) were quantified by ImmunoCAP. Mock-treated and IgG-depleted sera from patients tolerating hazelnuts in food challenges were compared for their inhibitory activity for binding of Cor a 1-IgE complexes to B cells. RESULTS: In total, 73% of the study population experienced food allergy, which was perennial in 86% of the affected individuals. The oral allergy syndrome was the main clinical manifestation. However, more than 58% of the patients also experienced food-induced rhinoconjunctivitis. Apples and hazelnuts were identified as the most frequent triggers. Food allergy correlated with IgE reactivity to Bet v 1 but not to Bet v 2. Mal d 1-specific and Cor a 1-specific IgG(4)/IgE ratios were significantly higher in food-tolerant individuals than individuals with food allergy. Sera from IgG(4)-positive food-tolerant patients possessed IgG-dependent IgE-inhibitory activity. CONCLUSION: Birch pollen-related food allergy is highly prevalent and often perennial. High food allergen-specific IgG(4)/IgE ratios seem associated with food tolerance, potentially because specific IgG(4) blocks IgE binding to food allergens. Thus, the presence of food allergen-specific IgG(4) antibodies is no diagnostic marker for birch pollen-related food allergy.

[Urticaria - the most frequent dermatological disease]. / Urtikaria - die häufigste dermatologische Erkrankung.

Urticaria is a very frequent disease. The life time risk to experience at least one episode of urticaria is around 15 - 25 %. This article summarizes the most important definitions, classifications and diagnostic procedures in urticaria, as well as the evidence based management of urticaria. The recommendations given in this article are in accordance with two recent position papers by the European Academy of Allergology and Clinical Immunology (EAACI), the Global Allergy and Asthma European Network (GA2LEN), the European Dermatology Forum (EDF), and the World Allergy Organization (WAO).

[Atopic dermatitis - current insights into path physiology and management]. / Neurodermitis.

Atopic eczema (AE) is a multifaktoriell skin disease caused by a variety of factors such as genetic conditions, alterated skin structure, immunologic deviations, psychological and environmental factors, among others. There are two main subtypes of AE, i.e. the IgE-associated ("extrinsic atopic eczema") and the non-IgE-associated type ("intrinsic atopic eczema") with different prognosis concerning the development of respiratory diseases ("atopy march"). The role of allergens varies: while in early childhood food allergens may play a role, mites and microbial antigens may become more relevant in adolescence and adulthood. Recently, it was demonstrated that Filaggrin is a major gene for atopic eczema. The altered skin structure and a deficiency in antimicrobial peptides favour colonization with Staphylococcus aureus; their enterotoxins with superantigenic activity stimulate activation of T cells and macrophages. Also sensitization to the yeast Malassezia spp. occurs almost exclusively in AE patients. So far, AE skin lesions are orchestrated by the local tissue expression of proinflammatory cytokines and chemokines with activation of T lymphocytes, dendritic cells, macrophages, keratinocytes, mast cells, and eosinophils which lead to the skin inflammatory responses. From the therapeutic point of view, a step wise approach using emollients as a basic treatment is recommended. Modern topical corticosteroids of moderate to medium potency applied once per day and only on several days per week offer an efficient anti-inflammatory treatment with moderate side effects. Topic immunomodulatory drugs (tacrolimus and pimecrolimus) have in addition substantially improved the treatment of AE. Proactive treatment approaches also in disease-free intervals may reduce exacerbations and total drug use. Phototherapy and wet dressings are both efficient and safe additional tools in more severe forms. For generalized severe forms systemic drugs such as Cyclosporin A are very helpful. Various Biologicals and antipruriginous substances are under clinical investigation and may add to an improved therapy in the future.

Component-resolved diagnosis of kiwifruit allergy with purified natural and recombinant kiwifruit allergens.

BACKGROUND: Kiwifruit is one of the most common causes of food allergic reactions. Component-resolved diagnostics may enable significantly improved detection of sensitization to kiwifruit. OBJECTIVE: To evaluate the use of individual allergens for component-resolved in vitro diagnosis of kiwifruit allergy. METHODS: Thirty patients with a positive double-blind placebo-controlled food challenge to kiwifruit, 10 atopic subjects with negative open provocation to kiwifruit, and 5 nonatopic subjects were enrolled in the study. Specific IgE to 7 individual allergens (nAct d 1-5 and rAct d 8-9) and allergen extracts was measured by ImmunoCAP. RESULTS: The diagnostic sensitivities of the commercial extract and of the sum of single allergens were 17% and 77%, respectively, whereas diagnostic specificities were 100% and 30%. A combination of the kiwi allergens Act d 1, Act d 2, Act d 4, and Act d 5 gave a diagnostic sensitivity of 40%, whereas diagnostic specificity remained high (90%). Exclusion of the Bet v 1 homolog recombinant (r) Act d 8 and profilin rAct d 9 from this allergen panel reduced sensitivity to 50% but increased specificity to 40%. Kiwifruit-monosensitized patients reacted more frequently (P < .001) with Act d 1 than polysensitized patients, whereas the latter group reacted more frequently with rAct d 8 (P = .004). CONCLUSION: Use of single kiwifruit allergen ImmunoCAP increases the quantitative test performance and diagnostic sensitivity compared with the commercial extract. Bet v 1 homolog and profilin are important allergens in pollen-related kiwifruit allergy, whereas actinidin is important in monoallergy to kiwifruit, in which symptoms are often more severe.

Ara h 8, a Bet v 1-homologous allergen from peanut, is a major allergen in patients with combined birch pollen and peanut allergy.

BACKGROUND: We recently described patients with soybean allergy mainly mediated by cross-reactivity to birch pollen allergens. A majority of those patients were reported to have peanut allergy. OBJECTIVE: We sought to study the occurrence of peanut allergy in patients allergic to birch pollen and characterized the Bet v 1-homologous peanut allergen Ara h 8. METHODS: Recombinant Ara h 8 was cloned with degenerated primers and expressed in Escherichia coli. Nine Swiss and 11 Dutch patients with peanut and birch pollen allergy and a positive double-blind, placebo-controlled food challenge result to peanut were investigated for IgE reactivity to birch pollen and purified peanut allergens and cross-reactivity between birch and peanut. Ara h 8 stability against digestion and roasting was assessed by means of RAST inhibition. The IgE cross-linking potency of Ara h 8 was tested on the basis of basophil histamine release. RESULTS: During double-blind, placebo-controlled food challenge, all patients experienced symptoms in the oral cavity, progressing to more severe symptoms in 40% of patients. CAP-FEIA detected recombinant (r) Ara h 8-specific IgE in 85%. IgE binding to Ara h 8 was inhibited by Bet v 1 in peanut extract immunoblotting and in RAST inhibition. In EAST inhibition recombinant rAra h 8 inhibited IgE binding to peanut in 4 of 7 tested patient sera. Antipeanut response was dominated by Ara h 8 in 12 of 17 tested patients. Furthermore, our results demonstrate a low stability of Ara h 8 to roasting and no stability to gastric digestion. Basophil histamine release with rAra h 8 was more than 20% in 5 of 7 tested sera. CONCLUSIONS: Peanut allergy might be mediated in a subgroup of our patients by means of cross-reaction of Bet v 1 with the homologous peanut allergen Ara h 8.

Soybean allergy in patients allergic to birch pollen: clinical investigation and molecular characterization of allergens.

BACKGROUND: Allergic reactions to legumes are generally thought to be acquired by means of primary sensitization through the gastrointestinal tract. Recently, Gly m 4 (starvation-associated message 22), a Bet v 1-related pathogenesis-related protein 10 from soy, was suggested to be an allergen in patients with allergic reactions to a dietary product containing a soy protein isolate. OBJECTIVE: We sought to evaluate the clinical relevance of Gly m 4 in subjects allergic to birch pollen with soy allergy and to assess the risk for subjects allergic to birch pollen to acquire soy allergy. METHODS: Twenty-two patients allergic to birch pollen with soy allergy confirmed by means of positive double-blind, placebo-controlled food challenge results (n = 16) or a convincing history (n = 6) were investigated for IgE reactivity to birch pollen and soy allergens by using the Pharmacia CAP system and immunoblot analysis. Cross-reactivity was assessed by means of enzyme allergosorbent test inhibition. Ninety-four patients with birch pollen allergy were interviewed to assess soy tolerance and screened for IgE reactivity to Gly m 4 by means of immunoblotting. The Gly m 4 content in soy foods and soybean varieties was investigated by means of quantitative evaluation of immunoblots. RESULTS: During double-blind, placebo-controlled food challenge, 10 patients experienced symptoms localized to the oral cavity, and 6 patients had a more severe reaction. CAP analysis revealed Gly m 4-specific IgE in 96% (21/22) of the patients. All patients had Bet v 1-specific IgE antibodies, and 23% (5/22) had positive Bet v 2 results. In IgE immunoblotting 25% (6/22) of the patients recognized soy profilin (Gly m 3), and 64% (14/22) recognized other soy proteins. IgE binding to soy was at least 80% inhibited by birch pollen and 60% inhibited by rGly m 4 in 9 of 11 sera tested. Seventy-one percent (67/94) of highly Bet v 1-sensitized patients with birch pollen allergy were sensitized to Gly m 4, and 9 (9.6%) of those patients reported soy allergy. The Gly m 4 content in soy products ranged between 0 and 70 ppm (milligrams per kilogram). CONCLUSIONS: Our results confirm that soybean is another birch pollen-related allergenic food. Gly m 4 is the major soy allergen for patients allergic to birch pollen with soy allergy. The content of Gly m 4 in soy food products strongly depends on the degree of food processing.

Component-resolved diagnosis with recombinant allergens in patients with cherry allergy.

BACKGROUND: In pollen-related food allergy, extracts for skin prick tests (SPTs) are often not standardized, and the test reliability is affected by false-negative reactions. OBJECTIVE: We sought to evaluate a panel of recombinant allergens (RAs) derived from one allergenic food for use in component-resolved in vivo diagnosis, taking cherry as a model food. METHODS: Seventy-nine subjects were included in the study: 24 Swiss patients (group 1) with a positive double-blind placebo-controlled food challenge result to cherries, 23 patients with birch pollen allergy but without cherry allergy (group 2), 23 nonatopic subjects (group 3), and 9 Spanish patients with a history of a cherry allergy (group 4). SPTs were performed in duplicate by using recombinant cherry allergens (Bet v 1-related allergen: recombinant (r) Pru av 1; profilin: rPru av 4; and lipid transfer protein: rPru av 3) in concentrations of 10, 50, and 100 microg/mL. Furthermore, IgE reactivity to rPru av 1, rPru av 4, and rPru av 3 was assessed by means of immunoblot analysis. RESULTS: SPT responses with rPru av 1, rPru av 4, and rPru av 3 were positive in 92%, 17%, and 4% of the patients in group 1; in 74%, 30%, and 0% of the patients in group 2; in 0%, 22%, and 89% of the patients in group 4; and negative for all nonatopic subjects (group 3). Thus the sensitivity of a positive SPT response to at least one of the 3 RAs was 96%. The specificities, negative predictive values, and positive predictive values with the 3 RAs were 100%, 96%, and 100% if calculated in relation to the nonatopic control group but 17%, 79%, and 60% when calculated in relation to the control group with birch pollen allergy. The correlation between SPT and immunoblotting results was excellent. Sensitization to rPru av 3 was associated with more severe symptoms than sensitization to rPru av 1. CONCLUSIONS: SPTs with RAs proved to be highly sensitive for diagnosis of cherry allergy. Component-resolved in vivo diagnosis with standardized amounts of stable RAs allows us to determine sensitization patterns directly, to correlate them with severity of clinical symptoms, and to analyze geographic differences.