{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T06:19:26Z","timestamp":1787811566255,"version":"build-2784847793"},"reference-count":51,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100019720","name":"GlaxoSmithKline Espa\u00f1a","doi-asserted-by":"publisher","award":["NCT04641741"],"award-info":[{"award-number":["NCT04641741"]}],"id":[{"id":"10.13039\/100019720","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["RYC2021\u2010032676\u2010I"],"award-info":[{"award-number":["RYC2021\u2010032676\u2010I"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Allergy"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Mepolizumab, an anti\u2010IL5 monoclonal antibody, effectively reduces exacerbations and improves disease control in severe eosinophilic asthma (SEA). While this treatment rapidly decreases blood eosinophil counts, some patients continue to experience asthma symptoms, suggesting that other features beyond eosinophil number contribute to disease persistence. In this work, we aim to characterize the molecular and functional signature of circulating eosinophils in SEA in response to mepolizumab therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed proteomic (LC\u2013MS\/MS) and targeted transcriptomic (Nanostring) analyses on isolated blood eosinophils from healthy individuals and SEA patients at baseline and after 4, 16 and 32\u2009weeks of treatment with mepolizumab. Western blot was used to validate selected genes and proteins.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Eosinophils from healthy donors and post\u2010treatment SEA patients exhibit lower levels of proteins related to cytoskeleton (e.g., GSN, DBNL, ARPC2 and ARPC3), suggesting a lower potential for migration and tissue extravasation. Several proteins (e.g., EPX and NCF2) and genes (e.g., CCL23 and SOCS3) directly involved in eosinophil effector functions, including ROS generation and degranulation, were significantly downregulated after mepolizumab treatment. The downregulation of GSN (actin\u2010binding protein), NCF2 (subunit of the NADPH oxidase complex) and EPX (eosinophil\u2010specific granule protein), was further validated by western blot.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our multi\u2010omic analysis suggests that mepolizumab reduces the migratory capacity and effector\u2010related molecular signatures of circulating eosinophils in SEA patients. Selected proteins, including GSN, NCF2 and EPX, may serve as candidate biomarkers for monitoring response to therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/all.70491","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T05:47:53Z","timestamp":1787809673000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mepolizumab Modifies Blood Eosinophil Proteome and Transcriptome in Severe Eosinophilic Asthma"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0932-4397","authenticated-orcid":false,"given":"Pablo","family":"Migu\u00e9ns\u2010Su\u00e1rez","sequence":"first","affiliation":[{"name":"Translational Research in Airway Diseases Group (TRIAD) Health Research Institute of Santiago de Compostela (IDIS)  Santiago de Compostela Galicia Spain"},{"name":"Department of Biochemistry and Molecular Biology, Faculty of Biology\u2010Biological Research Centre (CIBUS) Universidade de Santiago de Compostela  Santiago de Compostela Galicia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4540-8013","authenticated-orcid":false,"given":"Sara","family":"V\u00e1zquez\u2010Mera","sequence":"additional","affiliation":[{"name":"Translational Research in Airway Diseases Group (TRIAD) Health Research Institute of Santiago de Compostela (IDIS)  Santiago de Compostela Galicia Spain"},{"name":"Department of Biochemistry and Molecular Biology, Faculty of Biology\u2010Biological Research Centre (CIBUS) Universidade de Santiago de Compostela  Santiago de Compostela Galicia Spain"},{"name":"Department of Experimental Medical Science, Unit of Respiratory Immunopharmacology Lund University  Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Martelo\u2010Vidal","sequence":"additional","affiliation":[{"name":"Translational Research in Airway Diseases Group (TRIAD) Health Research Institute of Santiago de Compostela (IDIS)  Santiago de Compostela Galicia Spain"},{"name":"Department of Biochemistry and Molecular Biology, Faculty of Biology\u2010Biological Research Centre (CIBUS) Universidade de Santiago de Compostela  Santiago de Compostela Galicia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina Blanco","family":"Aparicio","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine University Hospital of A Coru\u00f1a  A Coru\u00f1a Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ux\u00edo Calvo","family":"\u00c1lvarez","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine University Hospital of Santiago de Compostela  Santiago de Compostela Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Coral Gonz\u00e1lez","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Department of Respiratory 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Calvo","family":"Henr\u00edquez","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology University Hospital of Santiago de Compostela  Santiago de Compostela Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susana B.","family":"Bravo","sequence":"additional","affiliation":[{"name":"Proteomic Platform Health Research Institute of Santiago de Compostela (IDIS)  Santiago de Compostela Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1842-148X","authenticated-orcid":false,"given":"Lena","family":"Uller","sequence":"additional","affiliation":[{"name":"Department of Experimental Medical Science, Unit of Respiratory Immunopharmacology Lund University  Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4647-1508","authenticated-orcid":false,"given":"Juan J.","family":"Nieto\u2010Fontarigo","sequence":"additional","affiliation":[{"name":"Translational Research in Airway Diseases Group (TRIAD) Health Research Institute of Santiago de Compostela (IDIS)  Santiago de Compostela Galicia Spain"},{"name":"Department of Biochemistry and Molecular Biology, Faculty of Biology\u2010Biological Research Centre (CIBUS) Universidade de Santiago de Compostela  Santiago de Compostela Galicia Spain"},{"name":"iARCUS Aquatic One Health Research Center\u2010University of Santiago de Compostela  Santiago de Compostela Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4738-215X","authenticated-orcid":false,"given":"Francisco J.","family":"Salgado","sequence":"additional","affiliation":[{"name":"Translational Research in Airway Diseases Group (TRIAD) Health Research Institute of Santiago de Compostela (IDIS)  Santiago de Compostela Galicia Spain"},{"name":"Department of Biochemistry and Molecular Biology, 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