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      Peanut-specific IgE antibodies in asymptomatic Ghanaian children possibly caused by carbohydrate determinant cross-reactivity

      research-article
      a , b , a , b , a , c , a , c , c , d , e , b , a , c , b ,
      The Journal of Allergy and Clinical Immunology
      Mosby
      Peanut allergy, skin prick testing, IgE, Sub-Saharan Africa, IgE cross-reactivity, cross-reactive carbohydrate determinants, helminth infections, basophil histamine release, EuroPrevall, aOR, Adjusted odds ratio, BHR, Basophil histamine release, CCD, Cross-reactive carbohydrate determinant, CRD, Component-resolved diagnostics, SEA, Soluble egg antigen, SPT, Skin prick test

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          Abstract

          Background

          The prevalence of peanut allergy has increased in developed countries, but little is known about developing countries with high peanut consumption and widespread parasitic infections.

          Objective

          We sought to investigate peanut allergy in Ghana.

          Methods

          In a cross-sectional survey among Ghanaian schoolchildren (n = 1604), data were collected on reported adverse reactions to peanut, peanut sensitization (serum specific IgE and skin reactivity), consumption patterns, and parasitic infections. In a subset (n = 43) IgE against Ara h 1, 2, 3, and 9 as well as cross-reactive carbohydrate determinants (CCDs) was measured by using ImmunoCAP. Cross-reactivity and biological activity were investigated by means of ImmunoCAP inhibition and basophil histamine release, respectively.

          Results

          Adverse reactions to peanut were reported in 1.5%, skin prick test reactivity in 2.0%, and IgE sensitization (≥0.35 kU/L) in 17.5% of participants. Moreover, 92.4% of those IgE sensitized to peanut (≥0.35 kU/L) had negative peanut skin prick test responses. Schistosoma haematobium infection was positively associated with IgE sensitization (adjusted odds ratio, 2.29; 95% CI, 1.37-3.86). In the subset IgE titers to Ara h 1, 2, 3, and 9 were low (<1.3 kU/L), except for 6 moderately strong reactions to Ara h 9. IgE against peanut was strongly correlated with IgE against CCDs ( r = 0.89, P < .0001) and could be almost completely inhibited by CCDs, as well as S haematobium soluble egg antigen. Moreover, IgE to peanut showed poor biological activity.

          Conclusions

          Parasite-induced IgE against CCDs might account largely for high IgE levels to peanut in our study population of Ghanaian schoolchildren. No evidence of IgE-mediated peanut allergy was found.

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          Most cited references35

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          Allergy, parasites, and the hygiene hypothesis.

          The increase of allergic diseases in the industrialized world has often been explained by a decline in infections during childhood. The immunological explanation has been put into the context of the functional T cell subsets known as T helper 1 (TH1) and T helper 2 (TH2) that display polarized cytokine profiles. It has been argued that bacterial and viral infections during early life direct the maturing immune system toward TH1, which counterbalance proallergic responses of TH2 cells. Thus, a reduction in the overall microbial burden will result in weak TH1 imprinting and unrestrained TH2 responses that allow an increase in allergy. This notion is contradicted by observations that the prevalence of TH1-autoimmune diseases is also increasing and that TH2-skewed parasitic worm (helminth) infections are not associated with allergy. More recently, elevations of anti-inflammatory cytokines, such as interleukin-10, that occur during long-term helminth infections have been shown to be inversely correlated with allergy. The induction of a robust anti-inflammatory regulatory network by persistent immune challenge offers a unifying explanation for the observed inverse association of many infections with allergic disorders.
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            The role of protein glycosylation in allergy.

            The asparagine-linked carbohydrate moieties of plant and insect glycoproteins are the most abundant environmental immune determinants. They are the structural basis of what is known as cross-reactive carbohydrate determinants (CCDs). Despite some structural variation, the two main motifs are the xylose and the core-3-linked fucose, which form the essential part of two independent epitopes. Plants contain both epitopes, insect glycoproteins only fucose. These epitopes and other fucosylated determinants are also found in helminth parasites where they exert remarkable immunomodulatory effects. About 20% or more of allergic patients generate specific anti-glycan IgE, which is often accompanied by IgG. Even though antibody-binding glycoproteins are widespread in pollens, foods and insect venoms, CCDs do not appear to cause clinical symptoms in most, if not all patients. When IgE binding is solely due to CCDs, a glycoprotein allergen thus can be rated as clinical irrelevant allergen. Low binding affinity between IgE and plant N-glycans now drops out as a plausible explanation for the benign nature of CCDs. This rather may result from blocking antibodies induced by an incidental 'immune therapy' ('glyco-specific immune therapy') exerted by everyday contact with plant materials, e.g. fruits or vegetables. The need to detect and suppress anti-CCD IgE without interference from peptide epitopes can be best met by artificial glycoprotein allergens. Hydroxyproline-linked arabinose (single beta-arabinofuranosyl residues) has been identified as a new IgE-binding carbohydrate epitope in the major mugwort allergen. However, currently the occurrence of this O-glycan determinant appears to be rather restricted. Copyright 2007 S. Karger AG, Basel.
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              Peanut allergy: Clinical and immunologic differences among patients from 3 different geographic regions.

              Peanut allergy affects persons from various geographic regions where populations are exposed to different dietary habits and environmental pollens. We sought to describe the clinical and immunologic characteristics of patients with peanut allergy from 3 countries (Spain, the United States, and Sweden) using a molecular component diagnostic approach. Patients with peanut allergy from Madrid (Spain, n = 50), New York (United States, n = 30), Gothenburg, and Stockholm (both Sweden, n = 35) were enrolled. Clinical data were obtained either from a specific questionnaire or gathered from chart reviews. IgE antibodies to peanut extract and the peanut allergens rAra h 1, 2, 3, 8 and 9, as well as to cross-reactive birch (rBet v 1) and grass (rPhl p 1, 5, 7, and 12) pollen allergens, were analyzed. American patients frequently had IgE antibodies to rAra h 1 to 3 (56.7% to 90.0%) and often presented with severe symptoms. Spanish patients recognized these 3 recombinant peanut allergens less frequently (16.0% to 42.0%), were more often sensitized to the lipid transfer protein rAra h 9 (60.0%), and typically had peanut allergy after becoming allergic to other plant-derived foods. Swedish patients detected rAra h 1 to 3 more frequently than Spanish patients (37.1% to 74.3%) and had the highest sensitization rate to the Bet v 1 homologue rAra h 8 (65.7%), as well as to rBet v 1 (82.9%). Spanish and Swedish patients became allergic to peanut at 2 years or later, whereas the American children became allergic around 1 year of age. Peanut allergy has different clinical and immunologic patterns in different areas of the world. Allergen component diagnostics might help us to better understand this complex entity. Copyright © 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
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                Author and article information

                Journal
                J Allergy Clin Immunol
                J. Allergy Clin. Immunol
                The Journal of Allergy and Clinical Immunology
                Mosby
                0091-6749
                1097-6825
                1 September 2013
                September 2013
                : 132
                : 3
                : 639-647
                Affiliations
                [a ]Department of Parasitology, Noguchi Memorial Institute for Medical Research, Accra, Ghana
                [b ]Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands
                [c ]Department of Experimental Immunology and Department of Otorhinolaryngology, Academic Medical Center, Amsterdam, The Netherlands
                [d ]Thermo Fisher Scientific, Uppsala, Sweden
                [e ]Servicio de Alergia, Hospital Clinico San Carlos, Madrid, Spain
                Author notes
                []Corresponding author: Maria Yazdanbakhsh, PhD, Department of Parasitology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. M.Yazdanbakhsh@ 123456lumc.nl
                Article
                YMAI10221
                10.1016/j.jaci.2013.04.023
                3765958
                23763976
                7e7c99fc-616e-4349-b59a-438162732b5c
                © 2013 Mosby, Inc.

                This document may be redistributed and reused, subject to certain conditions.

                History
                : 17 October 2012
                : 12 April 2013
                : 16 April 2013
                Categories
                Food, Drug, Insect Sting Allergy, and Anaphylaxis

                Immunology
                peanut allergy,skin prick testing,ige,sub-saharan africa,ige cross-reactivity,cross-reactive carbohydrate determinants,helminth infections,basophil histamine release,europrevall,aor, adjusted odds ratio,bhr, basophil histamine release,ccd, cross-reactive carbohydrate determinant,crd, component-resolved diagnostics,sea, soluble egg antigen,spt, skin prick test

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