{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T16:27:31Z","timestamp":1759336051673,"version":"build-2065373602"},"reference-count":68,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,8,10]],"date-time":"2025-08-10T00:00:00Z","timestamp":1754784000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004497","name":"Onderzoeksraad, KU Leuven","doi-asserted-by":"publisher","award":["C14\/23\/143","C3\/22\/054"],"award-info":[{"award-number":["C14\/23\/143","C3\/22\/054"]}],"id":[{"id":"10.13039\/501100004497","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["G036423N"],"award-info":[{"award-number":["G036423N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008792","name":"Novartis Pharma","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008792","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019771","name":"Rega Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100019771","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Adaptive IgE\u2010mediated reactions are faster than immune responses that depend on IgM, IgA, and IgG. Normal serum IgE concentrations are highly variable among individuals and extremely low in comparison with those of IgM and IgG. Omalizumab is a clinically approved monoclonal antibody that selectively binds free IgE, preventing allergy\u2010specific IgE from binding to Fc\u03b5RI expressed on mast cells and basophils, thereby inhibiting degranulation and mediator release. We aimed to evaluate proteolysis of IgE within the contexts of acute inflammations in\u00a0vitro and in patient samples and the biological effects of resulting IgE proteoforms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>IgE was subjected in\u00a0vitro to neutrophil proteases. Biochemical and biological IgE proteoform identification was performed and IgE receptor binding capacity and abundance in patient samples were evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Whereas IgG, IgA, and IgM are neutrophil protease\u2010resistant, the IgE heavy chain was cleaved in a bait region by these inflammation\u2010associated proteases. The cleavages occurred on both free and CD23\u2010bound IgE; however, not with Fc\u03b5RI\u2010bound IgE. Proteolysis generated two proteoforms: a large IgE cleavage fragment (IgEcl) and a smaller IgE carboxyterminal truncation fragment C\u03b5tr. Proteolysed IgE did not bind to its receptors. The C\u03b5tr fragment shared with chemokines high affinity to glycosaminoglycans (GAGs) and synergistically attracted neutrophils. The discovered bait region in IgE corresponded with a shared epitope recognized by omalizumab, and omalizumab prevented IgE proteolysis. Both IgEcl and C\u03b5tr were present in plasma samples from patients suffering from IgE\u2010mediated allergies, chronic spontaneous urticaria, and more abundantly in atopic dermatitis (AD) patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This work reveals new mechanistic insights into the immunobiology of IgE and the action of omalizumab with potential clinical impacts. Indeed, IgE\u2010specific cleavage by inflammation\u2010associated granulocyte proteinases may be an important feedback mechanism to control allergic responses.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.16622","type":"journal-article","created":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T06:34:34Z","timestamp":1754894074000},"page":"2781-2799","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["An Inflammation\u2010Associated Control Mechanism of Allergy by Proteolysis of <scp>IgE<\/scp>"],"prefix":"10.1111","volume":"80","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5182-6361","authenticated-orcid":false,"given":"Estefania","family":"Ugarte\u2010Berzal","sequence":"first","affiliation":[{"name":"Department of Microbiology, Immunology and Transplantation Laboratory of Immunobiology, Rega Institute for Medical Research, KU Leuven  Leuven 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Research Group, KU Leuven  Leuven Belgium"},{"name":"Department General Internal Medicine\u2010Allergy and Clinical Immunology University Hospitals Leuven  Leuven Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Guntermann","sequence":"additional","affiliation":[{"name":"Immunology Disease Area Novartis BioMedical Research  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rik","family":"Schrijvers","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Transplantation Allergy and Clinical Immunology Research Group, KU Leuven  Leuven Belgium"},{"name":"Department General Internal Medicine\u2010Allergy and Clinical Immunology University Hospitals Leuven  Leuven Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Proost","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Transplantation Laboratory 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