Search

Background: The Learning Early About Peanut allergy (LEAP) study has shown the effectiveness of early peanut introduction in prevention of peanut allergy (PA). In the Enquiring About Tolerance (EAT) study, a statistically significant reduction in PA was present only in per‐protocol (PP) analyses, which can be subject to bias. Objective: The aim of this study was to combine individual‐level data from the LEAP and EAT trials and provide robust evidence on the bias‐corrected, causal effect of early peanut introduction. Method: As part of the European Union‐funded iFAAM project, this pooled analysis of individual pediatric patient data combines and compares effectiveness and efficacy estimates of oral tolerance induction among different risk strata and analysis methods. Results: An intention‐to‐treat (ITT) analysis of pooled data showed a 75% reduction in PA (p <.0001) among children randomized to consume peanut from early infancy. A protective effect was present across all eczema severity groups, irrespective of enrollment sensitization to peanut, and across different ethnicities. Earlier age of introduction was associated with improved effectiveness of the intervention. In the pooled PP analysis, peanut consumption reduced the risk of PA by 98% (p <.0001). A causal inference analysis confirmed the strong PP effect (89% average treatment effect relative risk reduction p <.0001). A multivariable causal inference analysis approach estimated a large (100%) reduction in PA in children without eczema (p =.004). Conclusion: We demonstrate a significant reduction in PA with early peanut introduction in a large group of pooled, randomized participants. This significant reduction was demonstrated across all risk subgroups, including children with no eczema. Furthermore, our results point to increased efficacy of the intervention with earlier age of introduction. [ABSTRACT FROM AUTHOR]

Background: Bioaccessibility of food allergens may be a key determinant of allergic reactions. Objective: To develop a protocol allowing the detection of the major peanut allergen, Ara h 6, in the bloodstream following ingestion of low amounts of peanut and to compare Ara h 6 bioaccessibility by food matrix. We further assessed for differences in absorption in healthy versus peanut‐allergic volunteers. Methods: A blood pretreatment combining acidic shock and thermal treatment was developed. This protocol was then applied to blood samples collected from human volunteers (n = 6, healthy controls; n = 14, peanut‐allergic patients) at various time‐points following ingestion of increasing levels of peanut incurred in different food matrices (cookies, peanut butter and chocolate dessert). Immunodetection was performed using an in‐house immunoassay. Results: An original pretreatment protocol was optimized, resulting in irreversible dissociation of human antibodies‐Ara h 6 immune complex, thus rendering Ara h 6 accessible for its immunodetection. Ara h 6 was detected in samples from all volunteers following ingestion of 300‐1000 mg peanut protein, although variations in the kinetics of passage were observed between individuals and matrices. Interestingly, in peanut‐allergic subjects, Ara h 6 could be detected following ingestion of lower doses and at higher concentrations than in non‐allergic volunteers. Conclusions and Clinical Relevance: The kinetics and intensity of Ara h 6 passage in bloodstream depend on both individual and food matrix. Peanut‐allergic patients appear to demonstrate higher absorption rate, the clinical significance of which warrants further evaluation. [ABSTRACT FROM AUTHOR]

Background Allergy can be diagnosed using basophil tests. Several methods measuring basophil activation are available. This study aimed at comparing basophil activation test ( BAT), histamine release assay ( HR), and passive sensitization histamine release assay (passive HR) in the diagnosis of peanut allergy. Methods BAT, HR, and passive HR were performed on 11 peanut-allergic and 14 nonallergic subjects. Blood was incubated with peanut extract or anti-IgE and tests were performed as follows: BAT- CD63 upregulation was assessed by flow cytometry; HR-released histamine was quantified by a glass fiber-based fluorometric method; passive HR-IgE-stripped donor basophils were incubated with participants' serum and histamine release was quantified as HR. Results CDsens, a measure of basophil allergen sensitivity, was significantly higher for BAT (80.1±17.4) compared to HR (23.4±10.31) and passive HR (11.1±2.0). BAT, HR, and passive HR had a clinical sensitivity of 100%, 100%, and 82% and specificity of 100%, 100%, and 100%, respectively, when excluding inconclusive results. BAT identified 11 of 11 allergic patients, HR 10, and passive HR 9. Likewise, BAT recognized 12 of 14 nonallergic subjects, HR 10, and passive HR 13. However, the tests' diagnostic performances were not statistically different. Interestingly, nonreleasers in HR but not in BAT had lower basophil count compared to releasers (249 vs 630 counts/min). Conclusion BAT displayed a significantly higher CDsens compared to HR and passive HR. The basophil tests' diagnostic performances were not significantly different. Still, BAT could diagnose subjects with low basophil number in contrast to HR. [ABSTRACT FROM AUTHOR]

Background Data are lacking regarding the prevalence of food sensitization and probable food allergy among general population in India. We report the prevalence of sensitization and probable food allergy to 24 common foods among adults from general population in Karnataka, South India. Methodology The study was conducted in two stages: a screening study and a case-control study. A total of 11 791 adults in age group 20-54 were randomly sampled from general population in South India and answered a screening questionnaire. A total of 588 subjects (236 cases and 352 controls) participated in the case-control study involving a detailed questionnaire and specific IgE estimation for 24 common foods. Results A high level of sensitization (26.5%) was observed for most of the foods in the general population, higher than that observed among adults in Europe, except for those foods that cross-react with birch pollen. Most of the sensitization was observed in subjects who had total IgE above the median IgE level. A high level of cross-reactivity was observed among different pollens and foods and among foods. The prevalence of probable food allergy (self-reports of adverse symptoms after the consumption of food and specific IgE to the same food) was 1.2%, which was mainly accounted for cow's milk (0.5%) and apple (0.5%). Conclusion Very high levels of sensitization were observed for most foods, including those not commonly consumed in the general population. For the levels of sensitization, the prevalence of probable food allergy was low. This disassociation needs to be further explored in future studies. [ABSTRACT FROM AUTHOR]

To cite this article: Cochrane SA, Salt LJ, Wantling E, Rogers A, Coutts J, Ballmer-Weber BK, Fritsche P, Fernández-Rivas M, Reig I, Knulst A, Le T-M, Asero R, Beyer K, Golding M, Crevel R, Clare Mills EN, Mackie AR. Development of a standardized low-dose double-blind placebo-controlled challenge vehicle for the EuroPrevall Project. Allergy 2012; 67: 107-113. Abstract Background: Double-blind placebo-controlled food challenge (DBPCFC) is the gold standard for diagnosing food allergy. Standardized materials and protocols are essential for comparing DBPCFC results for multicentre studies such as EuroPrevall. This required the development and piloting of a standardized vehicle and low-dose protocol for confirming food allergy and determination of minimum eliciting doses (MEDs). Methods: A low-dose DBPCFC protocol was developed, with eight titrated protein doses from 3 μg to 1 g. This was delivered using a simple, microbiologically stable food base incorporating allergenic food ingredients manufactured at three sites and centrally distributed to clinical centres. Allergen blinding was assessed by a professional sensory testing panel using a triangle test. Homogeneity and allergen content were confirmed by ELISA and clinical efficacy was assessed in a pilot study, using celeriac and hazelnut as exemplars. Results: Celeriac and hazelnut ingredients were sufficiently blinded in the dessert. The dessert meals were successfully piloted with hazelnut in allergy clinics in Spain, the Netherlands and Italy and with celeriac and hazelnut in Zurich. The challenges elicited a range of subjective and objective reactions ranging in severity from mild itching of the oral mucosa to bronchospasm. Conclusions: A standardized challenge vehicle proven to sufficiently blind processed, powdered hazelnut and celeriac ingredients and that can be reproducibly manufactured has been developed. This pilot study shows that the vehicle is promising for the confirmation of food allergy and determination of MEDs in adults and children with body weight >28.8 kg (approximately 7-11 years old). [ABSTRACT FROM AUTHOR]

Grain development and its evolution in grasses remains poorly understood, despite cereals being our most important source of food. The grain, for which many grass species have been domesticated, is a single-seeded fruit with prominent and persistent endosperm. Brachypodium distachyon, a small wild grass, is being posited as a new model system for the temperate small grain cereals, but little is known about its endosperm development and how this compares with that of the domesticated cereals. A cellular and molecular map of domains within the developing Brachypodium endosperm is constructed. This provides the first detailed description of grain development in Brachypodium for the reference strain, Bd21, that will be useful for future genetic and comparative studies. Development of Brachypodium grains is compared with that of wheat. Notably, the aleurone is not regionally differentiated as in wheat, suggesting that the modified aleurone region may be a feature of only a subset of cereals. Also, the central endosperm and the nucellar epidermis contain unusually prominent cell walls that may act as a storage material. The composition of these cell walls is more closely related to those of barley and oats than to those of wheat. Therefore, although endosperm development is broadly similar to that of temperate small grain cereals, there are significant differences that may reflect its phylogenetic position between the Triticeae and rice. [ABSTRACT FROM PUBLISHER]

To cite this article: Wong GWK, Mahesh PA, Ogorodova L, Leung TF, Fedorova O, Holla AD, Fernandez-Rivas M, Clare Mills EN, Kummeling I, van Ree R, Yazdanbakhsh M, Burney P. The EuroPrevall-INCO surveys on the prevalence of food allergies in children from China, India and Russia: the study methodology. Allergy 2010; 65: 385–390. Background: Very little is known regarding the global variations in the prevalence of food allergies. The EuroPrevall-INCO project has been developed to evaluate the prevalence of food allergies in China, India and Russia using the standardized methodology of the EuroPrevall protocol used for studies in the European Union. The epidemiological surveys of the project were designed to estimate variations in the prevalence of food allergy and exposure to known or suspected risk factors for food allergy and to compare the data with different European countries. Methods: Random samples of primary schoolchildren were recruited from urban and rural regions of China, Russia and India for screening to ascertain possible adverse reactions to foods. Cases and controls were then selected to answer a detailed questionnaire designed to evaluate the possible risk factors of food allergies. Objective evidence of sensitisation including skin-prick test and serum specific IgE measurement was also collected. Results: More than 37 000 children from the three participating countries have been screened. The response rates for the screening phase ranged from 83% to 95%. More than 3000 cases and controls were studied in the second phase of the study. Furthur confirmation of food allergies by double blind food challenge was conducted. Conclusions: This will be the first comparative study of the epidemiology of food allergies in China, India, and Russia using the same standardized methodology. The findings of these surveys will complement the data obtained from Europe and provide insights into the development of food allergy. [ABSTRACT FROM AUTHOR]

The major 2S albumin allergen from Brazil nuts, Ber e 1, was subjected to gastrointestinal digestion using a physiologically relevantin vitromodel system either before or after heating (100 °C for 20 min). Whilst the albumin was cleaved into peptides, these were held together in a much larger structure even when digested by using a simulated phase 1 (gastric) followed by a phase 2 (duodenal) digestion system. Neither prior heating of Ber e 1 nor the presence of the physiological surfactant phosphatidylcholine affected the pattern of proteolysis. After 2 h of gastric digestion,≈ 25% of the allergen remained intact,≈ 50% corresponded to a large fragment ofMr 6400, and the remainder comprised smaller peptides. During duodenal digestion, residual intact 2S albumin disappeared quickly, but a modified form of the‘large fragment’ remained, even after 2 h of digestion, with a mass of≈ 5000 Da. The‘large fragment’ comprised several smaller peptides that were identified, by using different MS techniques, as deriving from the large subunit. In particular, sequences corresponding to the hypervariable region (Q37–M47) and to another peptide (P42–P69), spanning the main immunoglobulin E epitope region of 2S albumin allergens, were found to be largely intact following phase 1 (gastric) digestion. They also contained previously identified putative T-cell epitopes. These findings indicate that the characteristic conserved skeleton of cysteine residues of 2S albumin family and, particularly, the intrachain disulphide bond pattern of the large subunit, play a critical role in holding the core protein structure together even after extensive proteolysis, and the resulting structures still contain potentially active B- and T-cell epitopes. [ABSTRACT FROM AUTHOR]