{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T03:25:54Z","timestamp":1791257154511,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,3,26]],"date-time":"2014-03-26T00:00:00Z","timestamp":1395792000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Experimental Allergy"],"published-print":{"date-parts":[[2014,4]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background and objective<\/jats:title><jats:p>Goat's milk (<jats:styled-content style=\"fixed-case\">GM<\/jats:styled-content>) allergy associated with tolerance to cow's milk (<jats:styled-content style=\"fixed-case\">CM<\/jats:styled-content>) has been reported in patients without history of <jats:styled-content style=\"fixed-case\">CM<\/jats:styled-content> allergy and in <jats:styled-content style=\"fixed-case\">CM<\/jats:styled-content>\u2010allergic children successfully treated with oral immunotherapy. The IgE antibodies from <jats:styled-content style=\"fixed-case\">GM<\/jats:styled-content>\u2010allergic\/<jats:styled-content style=\"fixed-case\">CM<\/jats:styled-content>\u2010tolerant patients recognize caprine \u03b2\u2010casein (\u03b2cap) without cross\u2010reacting with bovine \u03b2\u2010casein (\u03b2bov) despite a sequence identity of 91%. In this study, we investigated the non\u2010cross\u2010reactive IgE\u2010binding epitopes of \u03b2cap.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Recombinant \u03b2cap was genetically modified by substituting caprine domains with the bovine counterparts and by performing site\u2010directed mutagenesis. We then evaluated the recognition of modified \u03b2cap by IgE antibodies from 11 GM\u2010allergic\/CM\u2010tolerant patients and 11 CM\u2010allergic patients or by monoclonal antibodies (<jats:styled-content style=\"fixed-case\">mA<\/jats:styled-content>b) raised against caprine caseins. The allergenic potency of modified \u03b2cap was finally assessed by degranulation tests of humanized rat basophil leukaemia (RBL)\u2010SX38 cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Non\u2010cross\u2010reactive epitopes of \u03b2cap were found in domains 44\u201388 and 130\u2013178. The substitutions A55T\/T63P\/L75P and P148H\/S152P induced the greatest decrease in IgE reactivity of GM\u2010allergic\/CM\u2010tolerant patients towards \u03b2cap. The pivotal role of threonine 63 was particularly revealed as its substitution also impaired the recognition of \u03b2cap by specific mAb, which could discriminate between \u03b2cap and \u03b2bov. The modified \u03b2cap containing the five substitutions was then unable to trigger the degranulation of RBL\u2010SX38 cells passively sensitized with IgE antibodies from GM\u2010allergic\/CM\u2010tolerant patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Although IgE\u2010binding epitopes are spread all over \u03b2cap, a non\u2010cross\u2010linking version of \u03b2cap was generated with only five amino acid substitutions and could thus provide new insight for the design of hypoallergenic variants.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cea.12261","type":"journal-article","created":{"date-parts":[[2013,12,23]],"date-time":"2013-12-23T08:02:48Z","timestamp":1387785768000},"page":"602-610","source":"Crossref","is-referenced-by-count":29,"title":["Goat's milk allergy without cow's milk allergy: suppression of non\u2010cross\u2010reactive epitopes on caprine 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