{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T20:10:23Z","timestamp":1778443823115,"version":"3.51.4"},"reference-count":46,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2017,7,14]],"date-time":"2017-07-14T00:00:00Z","timestamp":1499990400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DK034854"],"award-info":[{"award-number":["DK034854"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011684","name":"Crohn's and Colitis Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011684","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2017,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Food allergies are a growing health problem, and the development of therapies that prevent disease onset is limited by the lack of adjuvant\u2010free experimental animal models. We compared allergic sensitization in patients with food allergy or Wiskott\u2010Aldrich syndrome (<jats:styled-content style=\"fixed-case\">WAS<\/jats:styled-content>) and defined whether spontaneous disease in <jats:italic>Was<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice recapitulates the pathology of a conventional disease model and\/or human food allergy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Comparative Immuno<jats:styled-content style=\"fixed-case\">CAP ISAC<\/jats:styled-content> microarray was performed in patients with food allergy or <jats:styled-content style=\"fixed-case\">WAS<\/jats:styled-content>. Spontaneous food allergy in <jats:italic>Was<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice was compared to an adjuvant\u2010based model in wild\u2010type mice (<jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">OVA<\/jats:styled-content>\/alum). Intestinal and systemic anaphylaxis was assessed, and the role of the high\u2010affinity IgE Fc receptor (Fc\u03b5<jats:styled-content style=\"fixed-case\">RI<\/jats:styled-content>) in allergic sensitization was evaluated using <jats:italic>Was<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup><jats:italic>Fcer1a<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Polysensitization to food was detected in both <jats:styled-content style=\"fixed-case\">WAS<\/jats:styled-content> and food\u2010allergic patients which was recapitulated in the <jats:italic>Was<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> model. Oral administration of ovalbumin (OVA) in <jats:italic>Was<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice induced low titers of <jats:styled-content style=\"fixed-case\">OVA<\/jats:styled-content>\u2010specific IgE compared to the <jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">OVA<\/jats:styled-content>\/alum model. Irrespectively, 79% of <jats:italic>Was<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice developed allergic diarrhea following oral <jats:styled-content style=\"fixed-case\">OVA<\/jats:styled-content> challenge. Systemic anaphylaxis occurred in <jats:italic>Was<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice (95%) with a mortality rate &gt;50%. Spontaneous sensitization and intestinal allergy occurred independent of Fc\u03b5<jats:styled-content style=\"fixed-case\">RI<\/jats:styled-content> expression on mast cells (MCs) and basophils.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p><jats:italic>Was<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice provide a model of food allergy with the advantage of mimicking polysensitization and low food\u2010antigen IgE titers as observed in humans with clinical food allergy. This model will facilitate studies on aberrant immune responses during spontaneous disease development. Our results imply that therapeutic targeting of the IgE\/Fc\u03b5<jats:styled-content style=\"fixed-case\">RI<\/jats:styled-content> activation cascade will not affect sensitization to food.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.13219","type":"journal-article","created":{"date-parts":[[2017,6,10]],"date-time":"2017-06-10T14:32:41Z","timestamp":1497105161000},"page":"1916-1924","source":"Crossref","is-referenced-by-count":18,"title":["Spontaneous food allergy in <i>Was<\/i><sup><i>\u2212\/\u2212<\/i><\/sup> mice occurs independent of Fc\u03b5<scp>RI<\/scp>\u2010mediated mast cell activation"],"prefix":"10.1111","volume":"72","author":[{"given":"W. S.","family":"Lexmond","sequence":"first","affiliation":[{"name":"Department of Pediatrics Division of Gastroenterology, Hepatology and Nutrition Boston Children's Hospital Boston MA USA"},{"name":"Department of Medicine Harvard Medical School Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. A.","family":"Goettel","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Division of Gastroenterology, Hepatology and Nutrition Boston Children's Hospital Boston MA USA"},{"name":"Department of Medicine Harvard Medical School Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B. F.","family":"Sallis","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Division of Gastroenterology, Hepatology and Nutrition Boston Children's Hospital Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.","family":"McCann","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Division of Gastroenterology, Hepatology and Nutrition Boston Children's Hospital Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E. H. H. M.","family":"Rings","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics Erasmus Medical Center Erasmus University Rotterdam The Netherlands"},{"name":"University Medical Center Leiden Leiden University Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4019-5765","authenticated-orcid":false,"given":"E.","family":"Jensen\u2010Jarolim","sequence":"additional","affiliation":[{"name":"Center of Pathophysiology, Infectiology and Immunology Institute of Pathophysiology and Allergy Research Medical University of Vienna Vienna Austria"},{"name":"Comparative Medicine The Interuniversity Messerli Research Institute University of Veterinary Medicine Vienna, Medical University of Vienna, University of Vienna Vienna Austria"},{"name":"Allergy Care Allergy Diagnosis and Study Center Vienna Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Nurko","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Division of Gastroenterology, Hepatology and Nutrition Boston Children's Hospital Boston MA USA"},{"name":"Department of Medicine Harvard Medical School Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. 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