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Update on threshold doses of food allergens: implications for patients and the food industry.

Moneret-Vautrin, D.A., G. Kanny, 2004. Update on threshold doses of food allergens: implications for patients and the food industry. Curr Opin Allergy Clin Immunol. 4:215–219.

The purpose of this review is to bring the reader up to date on the importance of assessing a food’s lowest observed adverse effect level (LOAEL) with two aims. Firstly, to help industry choose tests with a level of sensitivity capable of detecting food allergens hidden in industrial products. Secondly, to specify protective measures for highly allergic individuals in order to prevent recurrent severe anaphylaxis. The review also seeks to highlight the present issues and unsolved questions. Recent findings Thanks to standardized oral-provocation tests (double-blind placebo-controlled food challenges), LOAELs have been identified for many IgE-dependent food allergies. Most studies concern the pediatric population. Data is available for milk, egg, peanut, wheat flour, and sesame. The LOAELs are commonly in the range of 1–2 mg of natural foods, representing a few hundred micrograms of protein. These minimal reactive doses characterize about 1% of people allergic to milk, egg, or peanut. The level at which no observed adverse effect is seen might be a few tens of micrograms of protein for peanut. At the present time, allergy to oil seems to be restricted to unrefined cold-pressed oils. Summary Concerning IgE-dependent food allergies, the threshold dose inducing symptoms is now known to vary a great deal according to the individual. A reactive dose of less than 65 mg characterizes 16 and 18% of patients allergic to egg or peanut. Less than 30 mg of milk proteins characterizes 5% of those allergic to milk. For milk, egg, and peanut, 1% of patients have a very low threshold, about 1 mg. Such data emphasize the necessity of using detection tests with a sensitivity better than 10 parts per million. The modifications of allergenicity undergone by protein ingredients that are now commonly introduced into industrially made products are not yet sufficiently known. A better knowledge of the reactive doses of these proteins is needed.

Human leucocyte antigen polymorphisms in nut-allergic patients in South Wales.

Hand, S., C. Darke, J. Thompson, C. Stingl, S. Rolf, K.P. Jones, B.H. Davies, 2004. Human leucocyte antigen polymorphisms in nut-allergic patients in South Wales. Clin Exp Allergy. 34:720–724.

Background: Peanuts and tree nuts are among the most common foods provoking severe allergic reactions including fatal anaphylaxis. However, little is known of the underlying genetic and immunological mechanisms involved. Objective: Based on findings in other allergic diseases, we have investigated whether specific human leucocyte antigens (HLA) are associated with nut allergy. Method Eighty-four patients presenting at the allergy clinic with symptoms of nut allergy were typed for the HLA Class I (HLA-A and B) and Class II (HLA-DRB1 and DQB1) loci by PCR using sequence-specific primers. Carriage frequencies were compared with 82 atopic non-nut-allergic subjects and 1798 random blood donors. Results: The frequency of HLA-B*07 (28.57%) and DRB1*11 (15.48%) was increased in the nutallergic patients compared to the atopic controls (12.20% and 3.66%, respectively) but not when compared to the blood donors (28.86% and 10.12%). DRB1*13 and DQB1*06 were both increased in frequency in the nut allergy patients over both the atopic and blood donor controls. However, none of these increased frequencies were significant when corrected for the number of comparisons undertaken. Conclusion: At HLA ‘2-digit resolution’ and with undifferentiated patients with nut allergy, there are no major disturbances in the frequency of HLA-A, B, DRB1 or DQB1 types. However, the difference in frequency of HLA-DRB1*11 between the nut allergy patients and the atopic controls merits further investigation as this may represent an important phenotypic relationship.

Use of the indirect competitive ELISA for the detection of Brazil nut in food products.

Clemente, A., S.J. Chambers, F. Lodi, C. Nicoletti, G.M. Brett, 2004. Use of the indirect competitive ELISA for the detection of Brazil nut in food products. Food Control. 15:65–69.

Food related allergic reactions following inadvertent ingestion are increasingly common, with nuts, including Brazil nut, placed firmly in the top 10 food groups whose presence within a product should be declared. The presence of hidden allergens as a result of adulteration or contamination of ingredients presents a problem for both the food industry and the consumer. A sensitive and specific immunoassay for Brazil nut is described with a limit of detection of 1 ppm. Based upon the detection of the abundant 2S protein the assay is suitable for detection of raw and roasted Brazil nut in a range of food matrices.

Multicenter study of emergency department visits for food allergies.

Clark, S., S. Allan Bock, T.J. Gaeta, B.E. Brenner, R.K. Cydulka, C.A. Camargo, on behalf of the Multicenter Airway Research Collaboration–8 Investigators, 2004. Multicenter study of emergency department visits for food allergies. J Allergy Clin Immunol. 113:347-352.

Background: Relatively little is known about the characteristics of patients who visit the emergency department (ED) for an acute allergic reaction. Although anaphylaxis guidelines suggest treatment with epinephrine, teaching about self-injectable epinephrine, and referral to an allergist, current ED management remains uncertain. Objective: The objective of this study was to describe the management of food-related acute allergic reactions. Methods: The Multicenter Airway Research Collaboration performed a chart review study in 21 North American EDs. Investigators reviewed a random sample of 678 charts of patients who presented with food allergy (International Classification of Diseases–ninth revision codes 693.1, 995.0, 995.3, and 995.60-995.69). Results: Patients had an average age of 29 years; the cohort was 57% female and 40% white. A variety of foods provoked the allergic reaction, including nuts (21%), crustaceans (19%), fruit (12%), and fish (10%). Although exposure to these foods can be life threatening, only 18% of patients came to the ED by ambulance. In the ED, 72% of patients received antihistamines, 48% received systemic corticosteroids, and 16% received epinephrine; 33% received respiratory treatments such as inhaled albuterol. Among patients with severe reactions (55% of total), 24% received epinephrine. Overall, 97% of patients were discharged to home. At ED discharge, 16% of patients were prescribed self-injectable epinephrine, and 12% were referred to an allergist. Conclusions: Although guidelines suggest specific approaches for the management of acute allergic reactions, ED concordance for food allergy appears low. These findings support a new collaboration between professional organizations in allergy and emergency medicine and the development of educational programs and materials for ED patients and staff.

Impact of γ-irradiation and thermal processing on the antigenicity of almond, cashew nut and walnut proteins.

Su, M., M. Venkatachalam, S.S. Teuber, K.H. Roux, S.K. Sathe, 2004. Impact of γ-irradiation and thermal processing on the antigenicity of almond, cashew nut and walnut proteins. J Sci Food Agric. 84:1119–1125.

Whole unprocessed almonds, cashew nuts and walnuts were each subjected to γ -irradiation (1, 5, 10 and 25 kGy) followed by heat processing including autoclaving (121°C, 15 psi for 15 and 30min), dry roasting (138 and 160°C for 30 min each, 168 and 177◦C for 12 min each), blanching (100°C for 5 and 10 min), oil roasting (191°C, 1min) and microwave heating (500W for 1 and 3min). Rabbit polyclonal antibodies were raised against each major protein isolated from defatted, but not subjected to γ -irradiation and/or any thermal processing, almond, cashew nut and walnut flours. Immunoreactivity of almond, cashew nut and walnut proteins soluble in borate saline buffer, normalised to 1mg protein ml1 for all samples, was determined by inhibition enzyme-linked immunosorbent assay (ELISA) and Western blotting. ELISAs and Western blotting experiments indicated that almond, cashew nut and walnut proteins exposed to γ -irradiation alone or followed by various thermal treatments remained antigenically stable.

A novel approach for the detection of potentially hazardous pepsin stable hazelnut proteins as contaminants in chocolate-based food.

Akkerdaas, J.H., M. Wensing, A.C. Knulst,O. Stephan, S.L. Hefle, R.C. Aalberse,R. van Ree, 2004. A novel approach for the detection of potentially hazardous pepsin stable hazelnut proteins as contaminants in chocolate-based food. J Agric Food Chem. 52:7726-7731.

Contamination of food products with pepsin resistant allergens is generally believed to be a serious threat to patients with severe food allergy. A sandwich type enzyme-linked immunosorbent assay (ELISA) was developed to measure pepsin resistant hazelnut protein in food products. Capturing and detecting rabbit antibodies were raised against pepsin-digested hazelnut and untreated hazelnut protein, respectively. The assay showed a detection limit of 0.7 ng/mL hazelnut protein or <1 µg hazelnut in 1 g food matrix and a maximum of 0.034% cross-reactivity (peanut). Chocolate samples spiked with 0.5-100 µg hazelnut/g chocolate showed a mean recovery of 97.3%. In 9/12 food products labeled “may contain nuts”, hazelnut was detected between 1.2 and 417 µg hazelnut/g food. It can be concluded that the application of antibodies directed to pepsin-digested food extracts in ELISA can facilitate specific detection of stable proteins that have the highest potential of inducing severe food anaphylaxis.

Update on food allergy

Sampson, H.A., 2004. Update on Food Allergy. J. Allergy Clin Immunol. 113:805-819.

Tremendous progress has been made in our understanding of food-based allergic disorders over the past 5 years. Recent epidemiologic studies suggest that nearly 4% of Americans are afflicted with food allergies, a prevalence much higher than appreciated in the past. In addition, the prevalence of peanut allergy was found to have doubled in American children less than 5 years of age in the past 5 years. Many food allergens have been characterized at the molecular level, which has contributed to our increased understanding of the immunopathogenesis of many allergic disorders and might soon lead to novel diagnostic and immunotherapeutic approaches. The management of food allergies continues to consist of educating patients on how to avoid relevant allergens, to recognize early symptoms of an allergic reaction in case of an accidental ingestion, and to initiate the appropriate emergency therapy. However, the recent successful clinical trial of anti-IgE therapy in patients with peanut allergy and the number of  immunomodulatory therapies in the pipeline provide real hope that we will soon be able to treat patients with food allergy.

Extensive in vitro cross-reactivity to seed storage proteins is present among walnut (Juglans) cultivars and species.

Comstock, S.S., G. McGranahan, W.R. Peterson, S.S. Teuber, 2004.  Extensive in vitro cross-reactivity to seed storage proteins is present among walnut (Juglans) cultivars and species. Clin Exp Allergy.34:1583-90.

BACKGROUND: Tree nuts, including English walnuts (Juglans regia), are sources of food allergens often associated with life-threatening allergic reactions. It is unknown if seed storage proteins from other Juglans species have IgE epitopes similar to those of the important English walnut allergens, Jug r 1 (2S albumin) and Jug r 2 (vicilin-like). OBJECTIVE: To screen for potential germplasm sources of hypoallergenic seed storage proteins of relevance in walnut food allergy. We sought to identify English walnut cultivars (cvs) or other Juglans species that showed decreased IgE binding to major seed storage proteins or an inability to cross-react with Jug r 1 or Jug r 2. METHODS: We determined if IgE in sera of patients who have had life-threatening systemic reactions to English walnut bound protein extracts from all tested walnut cvs (57 cvs total) or species (six) by Western immunoblot. Further, we used immunoblot inhibition to determine the in vitro cross-reactivity of Jug r 1 and Jug r 2, native and recombinant, with several walnut species. RESULTS: All walnut cvs and species contain allergenic proteins. Furthermore, as shown by in vitro immunoblot inhibition, the major walnut allergens in the species tested cross-reacted with those in J. regia cv. Chandler and J. nigra cv. Thomas extracts. CONCLUSIONS: Based on our findings, it is unlikely that a composite hypoallergenic walnut could be bred from available germplasm. In addition, patients with severe allergy to English walnut are likely to be clinically allergic to all commercial English walnut cvs and other closely related Juglans species.

The natural history of food allergy.

Wood, R.A., 2003. The natural history of food allergy. Pediatrics. 111:1631–1637.

The natural history of food allergy refers to the development of food sensitivities as well as the possible loss of the same food sensitivities over time. Most food allergy is acquired in the first 1 to 2 years of life, whereas the loss of food allergy is a far more variable process, depending on both the individual child and the specific food allergy. For example, whereas most milk allergy is outgrown over time, most allergies to peanuts and tree nuts are never lost. In addition, whereas some children may lose their milk allergy in a matter of months, the process may take as long as 8 or 10 years in other children. This review provides an overview of the natural history of food allergy and provides specific information on the natural course of the most common childhood food allergies.