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In the tropics, positive IgE tests are also prevalent, but rarely associated with ARD. Instead, IgE responses to ubiquitous cross\u2010reactive carbohydrate determinants (CCDs) on plant, insect and parasite glycoproteins, rather than to established major allergens, are dominant. Because anti\u2010CCD IgE has limited clinical relevance, it may impact ARD phenotyping and assessment of contribution of atopy to ARD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using an allergen extract\u2010based test, a glycan and an allergen (glyco)protein microarray, we mapped IgE fine specificity among Ugandan rural <jats:italic>Schistosoma mansoni<\/jats:italic> (<jats:italic>Sm<\/jats:italic>)\u2010endemic communities, proximate urban communities, and importantly in asthmatic and nonasthmatic schoolchildren.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Overall, IgE sensitization to extracts was highly prevalent (43%\u201073%) but allergen arrays indicated that this was not attributable to established major allergenic components of the extracts (0%\u201036%); instead, over 40% of all participants recognized CCD\u2010bearing components. Using glycan arrays, we dissected IgE responses to specific glycan moieties and found that reactivity to classical CCD epitopes (core \u03b2\u20101,2\u2010xylose, \u03b1\u20101,3\u2010fucose) was positively associated with sensitization to extracts, rural environment and <jats:italic>Sm<\/jats:italic> infection, but not with skin reactivity to extracts or sensitization to their major allergenic components. Interestingly, we discovered that reactivity to only a subset of core \u03b1\u20101,3\u2010fucose\u2010carrying N\u2010glycans was inversely associated with asthma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>CCD reactivity is not just an epiphenomenon of parasite exposure hampering specificity of allergy diagnostics; mechanistic studies should investigate whether specific CCD moieties identified here are implicated in the protective effect of certain environmental exposures against asthma.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.14469","type":"journal-article","created":{"date-parts":[[2020,6,22]],"date-time":"2020-06-22T14:47:17Z","timestamp":1592837237000},"page":"233-246","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Cross\u2010reactive carbohydrate determinant\u2010specific IgE obscures true atopy and exhibits \u237a\u20101,3\u2010fucose epitope\u2010specific inverse 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