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      Cor a 14, the allergenic 2S albumin from hazelnut, is highly thermostable and resistant to gastrointestinal digestion

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          Abstract

          Scope

          Allergens from nuts frequently induce severe allergic reactions in sensitive individuals. The aim of this study was to elucidate the physicochemical characteristics of natural Cor a 14, the 2S albumin from hazelnut.

          Methods and results

          Cor a 14 was purified from raw hazelnuts using a combination of precipitation and chromatographic techniques. The protein was analyzed using gel electrophoresis, MS, and far‐UV circular dichroism (CD) analyses. The immunoglobulin E (IgE) binding of native, heat‐treated, and in vitro digested Cor a 14 was studied. We identified two different Cor a 14 isoforms and showed microclipping at the C‐terminus. CD spectra at room temperature showed the typical characteristics of 2S albumins, and temperatures of more than 80°C were required to start unfolding of Cor a 14 demonstrating its high stability to heat treatment. In vitro digestion experiments revealed that Cor a 14 is resistant to proteolytic degradation. Native and heat‐treated protein was recognized by sera from hazelnut allergic patients. However, denaturation of the allergen led to significantly reduced IgE binding.

          Conclusion

          We identified two different isoforms of Cor a 14 displaying high stability under heating and gastric and duodenal conditions. Data from IgE‐binding experiments revealed the existence of both, linear and conformational epitopes.

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          Most cited references33

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          Prevalence of common food allergies in Europe: a systematic review and meta-analysis.

          Allergy to cow's milk, egg, wheat, soy, peanut, tree nuts, fish, and shellfish constitutes the majority of food allergy reactions, but reliable estimates of their prevalence are lacking. This systematic review aimed to provide up-to-date estimates of their prevalence in Europe.Studies published in Europe from January 1, 2000, to September 30, 2012, were identified from searches of four electronic databases. Two independent reviewers appraised the studies and extracted the estimates of interest. Data were pooled using random-effects meta-analyses. Fifty studies were included in a narrative synthesis and 42 studies in the meta-analyses. Although there were significant heterogeneity between the studies, the overall pooled estimates for all age groups of self-reported lifetime prevalence of allergy to cow's milk, egg, wheat, soy, peanut, tree nuts, fish, and shellfish were 6.0% (95% confidence interval: 5.7-6.4), 2.5% (2.3-2.7), 3.6% (3.0-4.2), 0.4% (0.3-0.6), 1.3% (1.2-1.5), 2.2% (1.8-2.5), and 1.3% (0.9-1.7), respectively. The prevalence of food-challenge-defined allergy to cow's milk, egg, wheat, soy, peanut, tree nuts, fish, and shellfish was 0.6% (0.5-0.8), 0.2% (0.2-0.3), 0.1% (0.01-0.2), 0.3% (0.1-0.4), 0.2% (0.2-0.3), 0.5% (0.08-0.8), 0.1% (0.02-0.2), and 0.1% (0.06-0.3), respectively. Allergy to cow's milk and egg was more common among younger children, while allergy to peanut, tree nuts, fish, and shellfish was more common among the older ones. There were insufficient data to compare the estimates of soy and wheat allergy between the age groups. Allergy to most foods, except soy and peanut, appeared to be more common in Northern Europe. In summary, the lifetime self-reported prevalence of allergy to common foods in Europe ranged from 0.1 to 6.0%. The heterogeneity between studies was high, and participation rates varied across studies reaching as low as <20% in some studies. Standardizing the methods of assessment of food allergies and initiating strategies to increase participation will advance this evidence base. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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            Sensitization to Cor a 9 and Cor a 14 is highly specific for a hazelnut allergy with objective symptoms in Dutch children and adults.

            Component-resolved diagnosis has been shown to improve the diagnosis of food allergy. We sought to evaluate whether component-resolved diagnosis might help to identify patients at risk of objective allergic reactions to hazelnut. A total of 161 hazelnut-sensitized patients were included: 40 children and 15 adults with objective symptoms on double-blind, placebo-controlled food challenges (DBPCFCs) and 24 adults with a convincing objective history were compared with 41 children and 41 adults with no or subjective symptoms on DBPCFCs (grouped together). IgE levels to hazelnut extract and single components were analyzed with ImmunoCAP. IgE levels to hazelnut extract were significantly higher in children with objective than with no or subjective symptoms. In 13% of children and 49% of adults with hazelnut allergy with objective symptoms, only sensitization to rCor a 1.04 was observed and not to other water-soluble allergens. Sensitization to rCor a 8 was rare, which is in contrast to rCor a 1. Sensitization to nCor a 9, rCor a 14, or both was strongly associated with hazelnut allergy with objective symptoms. By using adapted cutoff levels, a diagnostic discrimination between severity groups was obtained. IgE levels to either nCor a 9 of 1 kUA/L or greater or rCor a 14 of 5 kUA/L or greater (children) and IgE levels to either nCor a 9 of 1 kUA/L or greater or rCor a 14 of 1 kUA/L or greater (adults) had a specificity of greater than 90% and accounted for 83% of children and 44% of adults with hazelnut allergy with objective symptoms. Sensitization to Cor a 9 and Cor a 14 is highly specific for patients with objective symptoms in DBPCFCs as a marker for a more severe hazelnut allergic phenotype. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
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              Component-resolved in vitro diagnosis of hazelnut allergy in Europe.

              Food allergy to hazelnut occurs both with and without concomitant pollen allergy. We sought to evaluate a panel of hazelnut allergens for diagnosis of hazelnut allergy in Spain, Switzerland, and Denmark. Fifty-two patients with a positive double-blind, placebo-controlled food challenge result with hazelnuts; 5 patients with a history of anaphylaxis; 62 patients with pollen allergy but hazelnut tolerance; and 63 nonatopic control subjects were included. Serum IgE levels to hazelnut extract, recombinant hazelnut allergens (rCor a 1.04, rCor a 2, rCor a 8, rCor a 11), and native allergens (nCor a 9, nCor a Bd8K, nCor a Bd11K) were analyzed by means of ImmunoCAP. Among patients with hazelnut allergy, 91% (Switzerland/Spain, 100%; Denmark, 75%) had IgE to hazelnut extract, 75% to rCor a 1.04, 42% to rCor a 2, 28% to rCor a 8, and 2% to rCor a 11. The highest rate of sensitization to Cor a 1.04 was found in the northern regions (Switzerland/Denmark, 100%; Spain, 18%), whereas IgE to the lipid transfer protein rCor a 8 prevailed in Spain (Spain, 71%; Switzerland, 15%; Denmark, 5%). IgE to profilin rCor a 2 was equally distributed (40% to 45%). Among control subjects with pollen allergy, 61% had IgE to hazelnut extract, 69% to rCor a 1.04, 34% to rCor a 2, 10% to rCor a 8, and 6% to rCor a 11. Component-resolved in vitro analyses revealed substantial differences in IgE profiles of hazelnut allergic and hazelnut tolerant patients across Europe.
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                Author and article information

                Journal
                Mol Nutr Food Res
                Mol Nutr Food Res
                10.1002/(ISSN)1613-4133
                MNFR
                Molecular Nutrition & Food Research
                John Wiley and Sons Inc. (Hoboken )
                1613-4125
                1613-4133
                06 August 2015
                October 2015
                : 59
                : 10 ( doiID: 10.1002/mnfr.v59.10 )
                : 2077-2086
                Affiliations
                [ 1 ] Department of Pathophysiology and Allergy Research Center for Pathophysiology Infectiology and ImmunologyMedical University of Vienna ViennaAustria
                [ 2 ] VetCore FacilityUniversity of Veterinary Medicine ViennaAustria
                [ 3 ] Institute of Molecular Biosciences Structural BiologyUniversity of Graz GrazAustria
                Author notes
                [*] [* ] Correspondence: Karin Hoffmann‐Sommergruber

                E‐mail: karin.hoffmann@ 123456meduniwien.ac.at

                Article
                MNFR2442
                10.1002/mnfr.201500071
                4973671
                26178695
                1974905e-eac2-4c6d-95c5-4bee03792354
                © 2015 The Authors. Molecular Nutrition & Food Research published by Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim.

                This is an open access article under the terms of the Creative Commons Licence, which permits use and distribution in any medium, provided the original work is properly cited.

                History
                : 29 January 2015
                : 07 May 2015
                : 25 June 2015
                Page count
                Pages: 10
                Categories
                Research Article
                Research Articles
                Custom metadata
                2.0
                mnfr2442
                October 2015
                Converter:WILEY_ML3GV2_TO_NLMPMC version:4.9.4 mode:remove_FC converted:04.08.2016

                Nutrition & Dietetics
                allergen,cor a 14,food allergy,hazelnut (corylus avellana),2s albumin
                Nutrition & Dietetics
                allergen, cor a 14, food allergy, hazelnut (corylus avellana), 2s albumin

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