{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T23:31:42Z","timestamp":1792452702624,"version":"4.5.0"},"reference-count":54,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T00:00:00Z","timestamp":1734480000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T00:00:00Z","timestamp":1734480000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI19\/00044"],"award-info":[{"award-number":["PI19\/00044"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008061","name":"Fundaci\u00f3n Mutua Madrile\u00f1a","doi-asserted-by":"publisher","award":["AP177712021"],"award-info":[{"award-number":["AP177712021"]}],"id":[{"id":"10.13039\/100008061","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100031291","name":"Fundaci\u00f3n Universitaria San Pablo CEU","doi-asserted-by":"publisher","award":["PEJ\u20102023\u2010AI\/SAL\u2010GL\u201027622"],"award-info":[{"award-number":["PEJ\u20102023\u2010AI\/SAL\u2010GL\u201027622"]}],"id":[{"id":"10.13039\/100031291","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Biologics are becoming increasingly important in the management of severe asthma. However, little is known about the systemic immunometabolic consequences of Th2 response blockage.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To provide a better immunometabolic understanding of the effects of mepolizumab and omalizumab treatments by identifying potential biomarkers for monitoring.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this exploratory longitudinal study severe asthmatic patients were followed for 18\u2009months after initiating mepolizumab (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200936) or Omalizumab (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200920) treatment. Serum samples were collected before, 6, and 18\u2009months after treatment. Targeted omic approaches were performed to analyze inflammatory metabolites (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200935) and proteins (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200945). Multiomic integration was performed individually for each treatment applying supervised analysis Data Integration Analysis for Biomarker discovery using Latent cOmponents (DIABLO) framework. Then, potential biomarkers were confirmed using multivariate ROC analyses and correlated with clinical variables along treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>Mepolizumab and omalizumab were both effective (improved clinical variables) and showed different and specific metabolic and protein profiles in severe asthmatic patients during treatment. Multiomic integration and multivariate ROC analyses identified specific biomarkers, such as arachidonic acid, palmitoleic acid, oleic acid, propionylcarnitine, bilirubin, CCL11, and TNFSF10, which can explain the differences observed with Mepolizumab treatment over 18\u2009months and significantly correlate with clinical improvement. However, no significant biomolecules and no discriminative multivariate ROC curves were found for Omalizumab treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our results provide a comprehensive insight into the differential effects of mepolizumab and omalizumab on the immunometabolic kinetics of the inflammatory response in severe asthma. We identified a set of biomolecules with potential for monitoring mepolizumab treatment which could be useful for personalized medicine.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/all.16434","type":"journal-article","created":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T06:33:06Z","timestamp":1734503586000},"page":"1899-1911","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Multiomic Integration Analysis for Monitoring Severe Asthma Treated With Mepolizumab or Omalizumab"],"prefix":"10.1111","volume":"80","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4437-6758","authenticated-orcid":false,"given":"Nuria","family":"Contreras","sequence":"first","affiliation":[{"name":"Departamento de Ciencias M\u00e9dicas B\u00e1sicas, Facultad de Medicina, Instituto de Medicina Molecular Aplicada \u2013 Nemesio D\u00edez (IMMA\u2010ND) Universidad San Pablo\u2010CEU, CEU Universities  Madrid Spain"},{"name":"Centro de Metabol\u00f3mica y Bioan\u00e1lisis (CEMBIO), Facultad de Farmacia Universidad San Pablo\u2010CEU, CEU Universities  Boadilla del Monte Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8197-6107","authenticated-orcid":false,"given":"Andrea","family":"Escolar\u2010Pe\u00f1a","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias M\u00e9dicas B\u00e1sicas, Facultad de Medicina, Instituto de Medicina Molecular Aplicada \u2013 Nemesio D\u00edez (IMMA\u2010ND) Universidad San Pablo\u2010CEU, CEU Universities  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7924-5454","authenticated-orcid":false,"given":"Mar\u00eda I.","family":"Delgado\u2010Dolset","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias M\u00e9dicas B\u00e1sicas, Facultad de Medicina, Instituto de Medicina Molecular Aplicada \u2013 Nemesio D\u00edez (IMMA\u2010ND) Universidad San Pablo\u2010CEU, CEU Universities  Madrid Spain"},{"name":"Centro de Metabol\u00f3mica y Bioan\u00e1lisis (CEMBIO), Facultad de Farmacia Universidad San Pablo\u2010CEU, CEU Universities  Boadilla del Monte Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5941-8442","authenticated-orcid":false,"given":"Paloma","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias M\u00e9dicas B\u00e1sicas, Facultad de Medicina, Instituto de Medicina Molecular Aplicada \u2013 Nemesio D\u00edez (IMMA\u2010ND) Universidad San Pablo\u2010CEU, CEU Universities  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7875-7327","authenticated-orcid":false,"given":"David","family":"Obeso","sequence":"additional","affiliation":[{"name":"Centro de Metabol\u00f3mica y Bioan\u00e1lisis (CEMBIO), Facultad de Farmacia Universidad San Pablo\u2010CEU, CEU Universities  Boadilla del Monte Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3355-2798","authenticated-orcid":false,"given":"Elena","family":"Izquierdo","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias M\u00e9dicas B\u00e1sicas, Facultad de Medicina, Instituto de Medicina Molecular Aplicada \u2013 Nemesio D\u00edez (IMMA\u2010ND) Universidad San Pablo\u2010CEU, CEU Universities  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6809-2410","authenticated-orcid":false,"given":"Heleia Gonz\u00e1lez","family":"Cuervo","sequence":"additional","affiliation":[{"name":"Servicio de Alergia, Hospital Universitario de Gran Canaria Doctor Negr\u00edn Universidad de Las Palmas de Gran Canaria (ULPGC)  Las Palmas de Gran Canaria Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6878-9488","authenticated-orcid":false,"given":"Jos\u00e9 \u00c1ngel","family":"Cumplido","sequence":"additional","affiliation":[{"name":"Servicio de Alergia, Hospital Universitario de Gran Canaria Doctor Negr\u00edn Universidad de Las Palmas de Gran Canaria (ULPGC)  Las Palmas de Gran Canaria Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5379-5642","authenticated-orcid":false,"given":"Victoria","family":"M\u00fagica","sequence":"additional","affiliation":[{"name":"Servicio de Alergia Hospital Universitario de La Princesa, Instituto De Investigaci\u00f3n Sanitaria Princesa (IIS\u2010Princesa)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4297-4199","authenticated-orcid":false,"given":"Carolina","family":"Cisneros","sequence":"additional","affiliation":[{"name":"Servicio de Neumolog\u00eda Hospital Universitario de La Princesa, Instituto De Investigaci\u00f3n Sanitaria Princesa (IIS\u2010Princesa)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7868-7442","authenticated-orcid":false,"given":"Santiago","family":"Angulo\u2010D\u00edaz\u2010Parre\u00f1o","sequence":"additional","affiliation":[{"name":"Departamento de Matem\u00e1ticas y Ciencia de Datos Universidad San Pablo\u2010CEU, CEU Universities  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4722-491X","authenticated-orcid":false,"given":"Coral","family":"Barbas","sequence":"additional","affiliation":[{"name":"Centro de Metabol\u00f3mica y Bioan\u00e1lisis (CEMBIO), Facultad de Farmacia Universidad San Pablo\u2010CEU, CEU Universities  Boadilla del Monte Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2893-6594","authenticated-orcid":false,"given":"Carlos","family":"Blanco","sequence":"additional","affiliation":[{"name":"Servicio de Alergia Hospital Universitario de La Princesa, Instituto De Investigaci\u00f3n Sanitaria Princesa (IIS\u2010Princesa)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3047-8908","authenticated-orcid":false,"given":"Teresa","family":"Carrillo","sequence":"additional","affiliation":[{"name":"Servicio de Alergia, Hospital Universitario de Gran Canaria Doctor Negr\u00edn Universidad de Las Palmas de Gran Canaria (ULPGC)  Las Palmas de Gran Canaria Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5488-5700","authenticated-orcid":false,"given":"Domingo","family":"Barber","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias M\u00e9dicas B\u00e1sicas, Facultad de Medicina, Instituto de Medicina Molecular Aplicada \u2013 Nemesio D\u00edez (IMMA\u2010ND) Universidad San Pablo\u2010CEU, CEU Universities  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6652-2739","authenticated-orcid":false,"given":"Alma","family":"Villase\u00f1or","sequence":"additional","affiliation":[{"name":"Centro de Metabol\u00f3mica y Bioan\u00e1lisis (CEMBIO), Facultad de Farmacia Universidad San Pablo\u2010CEU, CEU Universities  Boadilla del Monte Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5057-5150","authenticated-orcid":false,"given":"Mar\u00eda M.","family":"Escribese","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias M\u00e9dicas B\u00e1sicas, Facultad de Medicina, Instituto de Medicina Molecular Aplicada \u2013 Nemesio D\u00edez (IMMA\u2010ND) Universidad San Pablo\u2010CEU, CEU Universities  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,18]]},"reference":[{"key":"e_1_2_9_2_1","volume-title":"Global Atlas of Asthma","author":"Agache I.","year":"2022"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2016.04.022"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202212\u20102302ED"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/cea.13790"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.637948"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.opresp.2020.03.005"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.603312"},{"key":"e_1_2_9_9_1","unstructured":"Global Initiative for Asthma (GINA) \u201cGlobal Strategy for Asthma Management and Prevention \u201d2024 http:\/\/www.ginasthma.org."},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1177\/1753466618810192"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201810\u20101944CI"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.alit.2019.01.004"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.14221"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2021.01.011"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.13850"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.alit.2020.01.004"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/cea.13694"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1183\/20734735.0301\u20102019"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.alit.2017.02.003"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2016.08.008"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2017.10.005"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.15412"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10040761"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00408\u2010020\u201000379\u20106"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1002536"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.15385"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.15192"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/cea.13991"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.13563"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/metabo12070592"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab394"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty1054"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu393"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.13806"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102222.2011.03929.x"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2017.00093"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.15867"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2016.25"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010019\u201038483\u20100"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931\u2010021\u201001733\u20109"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1177\/1753466620929231"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1183\/23120541.00931\u20102023"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.5159\u201020"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1080\/02770903.2020.1766061"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2017.12.002"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00396\u20102021"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.3390\/medicina55060284"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2020.113925"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.14295"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mucimm.2024.03.005"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0140697"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.14800\/ics.1178"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11081161"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI36130"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3314"}],"container-title":["Allergy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/all.16434","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/all.16434","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/all.16434","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T03:43:10Z","timestamp":1782013390000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/all.16434"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,18]]},"references-count":54,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2025,7]]}},"alternative-id":["10.1111\/all.16434"],"URL":"https:\/\/doi.org\/10.1111\/all.16434","archive":["Portico"],"relation":{},"ISSN":["0105-4538","1398-9995"],"issn-type":[{"value":"0105-4538","type":"print"},{"value":"1398-9995","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,18]]},"assertion":[{"value":"2024-06-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}