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Crystal structure of Prunin-1, a major component of the almond (Prunus dulcis) allergen amandin.

Jin,T., S.M. Albillos, F. Guo, A. Howard, T.-J. Fu, M.H. Kothary, Y.-Z. Zhang, 2009. Crystal structure of Prunin-1, a major component of the almond (Prunus dulcis) allergen amandin. J Agric Food Chem.  57:8643–8651.

Seed storage proteins are accumulated during seed development and act as a reserve of nutrition for seed germination and young sprout growth. Plant seeds play an important role in human nutrition by providing a relatively inexpensive source of protein. However, many plant foods contain allergenic proteins, and the number of people suffering from food allergies has increased rapidly in recent years. The 11S globulins are the most widespread seed storage proteins, present in monocotyledonous and dicotyledonous seeds as well as in gymnosperms (conifers) and other spermatophytes. This family of proteins accounts for a number of known major food allergens. They are of interest to both the public and industry due to food safety concerns. Because of the interests in the structural basis of the allergenicity of food allergens, we sought to determine the crystal structure of Pru1, the major component of the 11S storage protein from almonds. The structure was refined to 2.4 Å, and the R/Rfree for the final refined structure is 17.2/22.9. Pru1 is a hexamer made of two trimers. Most of the back-to-back trimer-trimer association was contributed by monomer-monomer interactions. An α helix (helix 6) at the C-terminal end of the acidic domain of one of the interacting monomers lies at the cleft of the two protomers. The residues in this helix correspond to a flexible region in the peanut allergen Ara h 3 that encompasses a previously defined linear IgE epitope.

Threshold dose for peanut: Risk characterization based upon published results from challenges of peanut-allergic individuals.

Taylor, S.L., R.W.R. Crevel, D. Sheffield, J. Kabourek, J. Baumert, 2009. Threshold dose for peanut: Risk characterization based upon published results from challenges of peanut-allergic individuals. Food Chem Toxicol. 47:1198–1204.

Population thresholds for peanut are unknown. However, lowest- and no-observed adverse effect levels (LOAELs and NOAELs) are published for an unknown number of peanut-allergic individuals. Publications were screened for LOAELs and NOAELs from blinded, low-dose oral challenges. Data were obtained from 185 peanut-allergic individuals (12 publications). Data were analyzed by interval-censoring survival analysis and three probability distribution models fitted to it (Log-Normal, Log-Logistic, and Weibull) to estimate the ED10. All three models described the data well and provided ED10’s in close agreement: 17.6, 17.0, and 14.6 mg of whole peanut for the Log-Normal, Log-Logistic, and Weibull models, respectively. The 95% lower confidence intervals for the ED10’s were 9.2, 8.1, and 6.0 mg of whole peanut for the Log-Normal, Log-Logistic, and Weibull models, respectively. The modeling of individual NOAELs and LOAELs identified from three different types of published studies – diagnostic series, threshold studies, and immunotherapy trials – yielded significantly different whole peanut ED10’s of 11.9 mg for threshold studies, 18.0 mg for diagnostic series and 65.5 mg for immunotherapy trials; patient selection and other biases may have influenced the estimates. These data and risk assessment models provide the type of information that is necessary to establish regulatory thresholds for peanut.

Peanut and tree nut allergy in childhood.

Skripak, J.M., R.A. Wood, 2008. Peanut and tree nut allergy in childhood. Pediatr Allergy Immunol. 19:368–373.

Peanut and tree nut allergies present multiple challenges in their presentation and management. These challenges have become increasingly relevant in recent years, as these allergies appear to have become more common. An estimated 1–2% of the population in the USA is allergic to peanut or tree nuts. Peanut allergy typically presents with symptoms in one of the first few exposures to peanut. Diagnosis is based on clinical history along with skin prick test, or quantitation of allergen-specific immunoglobulin E (IgE), and oral food challenges when indicated. Once the diagnosis is confirmed, the only current management approach is strict avoidance of the food. This is clearly an imperfect option as it can be difficult to avoid completely peanut and tree nuts and accidental exposures are not uncommon. Only about 20% of those with peanut allergy, and <10% of those with tree nut allergy, are reported to acquire tolerance. Additionally, peanut allergy can recur, with one study finding a recurrence rate of 8%. Peanut and tree nuts are the foods most frequently associated with fatal episodes of anaphylaxis. This is of particular concern in adolescents and young adults, among whom life-threatening and fatal food allergy-related reactions are most common.

Epidemiologic risks for food allergy.

Gideon Lack, 2008.  Epidemiologic risks for food allergy. J Allergy Clin Immunol. 121:1331-6.

This article reviews possible risk factors and theories for the development of food allergy. It is noted that previous strategies to prevent food allergy through allergen avoidance during pregnancy, breast-feeding, and infancy have more recently been called into question. Alternative hypotheses are examined with respect to food allergy, namely the hygiene hypothesis, the dietary fat hypothesis, the antioxidant hypothesis, and the vitamin D hypotheses. An alternative hypothesis is proposed, suggesting that sensitization to allergen occurs through environmental exposure to allergen through the skin and that consumption of food allergen induces oral tolerance. This hypothesis provides a possible explanation for the close link between eczema and the development of food allergies. It also suggests novel interventional strategies to prevent the development of food allergies.

Analysis of food-allergic and anaphylactic events in the National Electronic Injury Surveillance System.

Ross, M.P., M. Ferguson, D. Street, K. Klontz, T. Schroeder, S. Luccioli, 2008. Analysis of food-allergic and anaphylactic events in the National Electronic Injury Surveillance System. J Allergy Clin Immunol. 121:166-71.

Background: The National Electronic Injury Surveillance System (NEISS) captures a nationally representative probability sample from hospital emergency departments (EDs) in the United States. Objective: Emergency department data from NEISS were analyzed to assess the magnitude and severity of adverse events attributable to food allergies. Methods: Emergency department events describing food-related allergic symptomatology were identified from 34 participating EDs from August 1 to September 30, 2003. Results: Extrapolation of NEISS event data predicts a total of 20,821 hospital ED visits, 2333 visits for anaphylaxis, and 520 hospitalizations caused by food allergy in the United States during the 2-month study period. The median age was 26 years; 24% of visits involved children ≤5 years old. Shellfish was the most frequently implicated food in persons ≥6 years old, whereas children ≤5 years old experienced more events from eggs, fruit, peanuts, and tree nuts. There were no reported deaths. Review of medical records found that only 19% of patients received epinephrine, and, using criteria established by a 2005 anaphylaxis symposium, 57% of likely anaphylactic events did not have an ED diagnosis of anaphylaxis. Conclusion: Analysis of NEISS data may be a useful tool for assessing the magnitude and severity of food-allergic events. A criteria-based review of medical records suggests underdiagnosis of anaphylactic events in EDs.

The use of serum-specific IgE measurements for the diagnosis of peanut, tree nut, and seed allergy.

Maloney, J.M., M. Rudengren, S. Ahlstedt, S.A. Bock, H.A. Sampson, 2008. The use of serum-specific IgE measurements for the diagnosis of peanut, tree nut, and seed allergy. J Allergy Clin Immunol. 122:145-151.

Background: The gold standard for diagnosing food allergy is the double-blind, placebo-controlled food challenge. Diagnostic food-specific IgE levels might assist in diagnosing food allergies and circumventing the need for food challenges. Objectives: The purpose of this study was to determine the utility of food-specific IgE measurements for identifying symptomatic peanut, tree nut, and seed allergies and to augment what is known about the relationships among these foods. Methods: Patients referred for suspected peanut or tree nut allergies answered a questionnaire about their perceived food allergies. Allergen-specific diagnoses were based on questionnaire, medical history, and, when relevant, skin prick tests and serum specific IgE levels. Sera from the patients were analyzed for specific IgE antibodies to peanuts, tree nuts, and seeds by using ImmunoCAP Specific IgE (Phadia, Inc, Uppsala, Sweden). Results: Three hundred twenty-four patients (61% male; median age, 6.1 years; range, 0.2-40.2 years) were  evaluated. The patients were highly atopic (57% with atopic dermatitis and 58% with asthma). The majority of patients with peanut allergy were sensitized to tree nuts (86%), and 34% had documented clinical allergy. The relationship between diagnosis and allergen-specific IgE levels were estimated by using logistic regression. Diagnostic decision points are suggested for peanut and walnut. Probability curves were drawn for peanut, sesame, and several tree nuts. High correlations were found between cashew and pistachio and between pecan and walnut. Conclusions: Quantification of food-specific IgE is a valuable tool that will aid in the diagnosis of symptomatic food allergy and might decrease the need for double-blind, placebo-controlled food challenges.

Epidemiologic risks for food allergy.

Lack, G., 2008. Epidemiologic risks for food allergy. J Allergy Clin Immunol. 121:1331-1336.

This article reviews possible risk factors and theories for the development of food allergy. It is noted that previous strategies to prevent food allergy through allergen avoidance during pregnancy, breast-feeding, and infancy have more recently been called into question. Alternative hypotheses are examined with respect to food allergy, namely the hygiene hypothesis, the dietary fat hypothesis, the antioxidant hypothesis, and the vitamin D hypotheses. An alternative hypothesis is proposed, suggesting that sensitization to allergen occurs through environmental exposure to allergen through the skin and that consumption of food allergen induces oral tolerance. This hypothesis provides a possible explanation for the close link between eczema and the development of food allergies. It also suggests novel interventional strategies to prevent the development of food allergies

Purification, identification and preliminary crystallographic studies of Pru du amandin, an allergenic protein from Prunus dulcis.

Gaur, V., D.K. Sethi, D.M. Salunke, 2008. Purification, identification and preliminary crystallographic studies of Pru du amandin, an allergenic protein from Prunus dulcis. Acta Crystallogr Sect F Struct Biol Cryst Commun. F64: 32–35.

Food allergies appear to be one of the foremost causes of hypersensitivity reactions. Nut allergies account for most food allergies and are often permanent. The 360 kDa hexameric protein Pru du amandin, a known allergen, was purified from almonds (Prunus dulcis) by ammonium sulfate fractionation and ionexchange chromatography. The protein was identified by a BLAST homology search against the nonredundant sequence database. Pru du amandin belongs to the 11S legumin family of seed storage proteins characterized by the presence of a cupin motif. Crystals were obtained by the hanging-drop vapour-diffusion method. The crystals belong to space group P41 (or P43), with unit-cell parameters a = b = 150.7, c = 164.9Å.

Early consumption of peanuts in infancy is associated with a low prevalence of peanut allergy.

Du Toit, G., Y. Katz, P. Sasieni, D. Mesher, S.J. Maleki, H.R. Fisher, A.T. Fox, V. Turcanu, T. Amir, G. Zadik-Mnuhin, A. Cohen, I. Livne, G. Lack, 2008. Early consumption of peanuts in infancy is associated with a low prevalence of peanut allergy. J Allergy Clin Immunol. 122:978-985.

Background: Despite guidelines recommending avoidance of peanuts during infancy in the United Kingdom (UK), Australia, and, until recently, North America, peanut allergy (PA) continues to increase in these countries. Objective: We sought to determine the prevalence of PA among Israeli and UK Jewish children and evaluate the relationship of PA to infant and maternal peanut consumption. Methods: A clinically validated questionnaire determined the prevalence of PA among Jewish schoolchildren (5171 in the UK and 5615 in Israel). A second validated questionnaire assessed peanut consumption and weaning in Jewish infants (77 in the UK and 99 in Israel). Results: The prevalence of PA in the UK was 1.85%, and the prevalence in Israel was 0.17% (P < .001). Despite accounting for atopy, the adjusted risk ratio for PA between countries was 9.8 (95% CI, 3.1-30.5) in primary school children. Peanut is introduced earlier and is eaten more frequently and in larger quantities in Israel than in the UK. The median monthly consumption of peanut in Israeli infants aged 8 to 14 months is 7.1 g of peanut protein, and it is 0 g in the UK (P < .001). The median number of times peanut is eaten per month was 8 in Israel and 0 in the UK (P < .0001). Conclusions: We demonstrate that Jewish children in the UK have a prevalence of PA that is 10-fold higher than that of Jewish children in Israel. This difference is not accounted for by differences in atopy, social class, genetic background, or peanut allergenicity. Israeli infants consume peanut in high quantities in the first year of life, whereas UK infants avoid peanuts. These findings raise the question of whether early introduction of peanut during infancy, rather than avoidance, will prevent the development of PA.

Purification, crystallization and preliminary X-ray characterization of Prunin-1, a major component of the almond (Prunus dulcis) allergen amandin.

Albillos, S.M., T. Jin, A. Howard, Y. Zhang, M.H. Kothary, T.-J. Fu, 2008. Purification, crystallization and preliminary X-ray characterization of Prunin-1, a major component of the almond (Prunus dulcis) allergen amandin. J Agric Food Chem. 56(13):5352-5358.

The 11S globulins from plant seeds account for a number of major food allergens. Because of the interest in the structural basis underlying the allergenicity of food allergens, we sought to crystallize the main 11S seed storage protein from almond (Prunus dulcis). Prunin-1 (Pru1) was purified from defatted almond flour by water extraction, cryoprecipitation, followed by sequential anion exchange, hydrophobic interaction, and size exclusion chromatography. Single crystals of Pru1 were obtained in a screening with a crystal screen kit, using the hanging-drop vapor diffusion method. Diffraction quality crystals were grown after optimization. The Pru1 crystals diffracted to at least 3.0 Å and belong to the tetragonal space group P4122, with unit cell parameters of a = b = 150.912 Å, c = 165.248 Å. Self-rotation functions and molecular replacement calculations showed that there are three molecules in the asymmetry unit with water content of 51.41%. The three Pru1 protomers are related by a noncrystallographic 3-fold axis and they form a doughnut-shaped trimer. Two prunin trimers form a homohexamer. Elucidation of prunin structure will allow further characterization of the allergenic features of the 11S protein allergens at the molecular level.