Nuria Contreras, Andrea Escolar‐Peña, María I. Delgado‐Dolset, Paloma Fernández, David Obeso, Elena Izquierdo, Heleia González Cuervo, José Ángel Cumplido, Victoria Múgica, Carolina Cisneros, Santiago Angulo‐Díaz‐Parreño, Coral Barbas, Carlos Blanco, Teresa Carrillo, Domingo Barber, Alma Villaseñor, María M. Escribese
{"title":"监测美泊利珠单抗或奥马珠单抗治疗的严重哮喘的多组学整合分析","authors":"Nuria Contreras, Andrea Escolar‐Peña, María I. Delgado‐Dolset, Paloma Fernández, David Obeso, Elena Izquierdo, Heleia González Cuervo, José Ángel Cumplido, Victoria Múgica, Carolina Cisneros, Santiago Angulo‐Díaz‐Parreño, Coral Barbas, Carlos Blanco, Teresa Carrillo, Domingo Barber, Alma Villaseñor, María M. Escribese","doi":"10.1111/all.16434","DOIUrl":null,"url":null,"abstract":"RationaleBiologics are becoming increasingly important in the management of severe asthma. However, little is known about the systemic immunometabolic consequences of Th2 response blockage.ObjectivesTo provide a better immunometabolic understanding of the effects of mepolizumab and omalizumab treatments by identifying potential biomarkers for monitoring.MethodsIn this exploratory longitudinal study severe asthmatic patients were followed for 18 months after initiating mepolizumab (<jats:italic>n</jats:italic> = 36) or Omalizumab (<jats:italic>n</jats:italic> = 20) treatment. Serum samples were collected before, 6, and 18 months after treatment. Targeted omic approaches were performed to analyze inflammatory metabolites (<jats:italic>n</jats:italic> = 35) and proteins (<jats:italic>n</jats:italic> = 45). 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.Measurements and Main ResultsMepolizumab 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 months and significantly correlate with clinical improvement. However, no significant biomolecules and no discriminative multivariate ROC curves were found for Omalizumab treatment.ConclusionsOur 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.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"54 1","pages":""},"PeriodicalIF":12.6000,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Multiomic Integration Analysis for Monitoring Severe Asthma Treated With Mepolizumab or Omalizumab\",\"authors\":\"Nuria Contreras, Andrea Escolar‐Peña, María I. Delgado‐Dolset, Paloma Fernández, David Obeso, Elena Izquierdo, Heleia González Cuervo, José Ángel Cumplido, Victoria Múgica, Carolina Cisneros, Santiago Angulo‐Díaz‐Parreño, Coral Barbas, Carlos Blanco, Teresa Carrillo, Domingo Barber, Alma Villaseñor, María M. Escribese\",\"doi\":\"10.1111/all.16434\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"RationaleBiologics are becoming increasingly important in the management of severe asthma. However, little is known about the systemic immunometabolic consequences of Th2 response blockage.ObjectivesTo provide a better immunometabolic understanding of the effects of mepolizumab and omalizumab treatments by identifying potential biomarkers for monitoring.MethodsIn this exploratory longitudinal study severe asthmatic patients were followed for 18 months after initiating mepolizumab (<jats:italic>n</jats:italic> = 36) or Omalizumab (<jats:italic>n</jats:italic> = 20) treatment. Serum samples were collected before, 6, and 18 months after treatment. Targeted omic approaches were performed to analyze inflammatory metabolites (<jats:italic>n</jats:italic> = 35) and proteins (<jats:italic>n</jats:italic> = 45). 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.Measurements and Main ResultsMepolizumab 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 months and significantly correlate with clinical improvement. However, no significant biomolecules and no discriminative multivariate ROC curves were found for Omalizumab treatment.ConclusionsOur 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.\",\"PeriodicalId\":122,\"journal\":{\"name\":\"Allergy\",\"volume\":\"54 1\",\"pages\":\"\"},\"PeriodicalIF\":12.6000,\"publicationDate\":\"2024-12-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Allergy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1111/all.16434\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ALLERGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Allergy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/all.16434","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ALLERGY","Score":null,"Total":0}
Multiomic Integration Analysis for Monitoring Severe Asthma Treated With Mepolizumab or Omalizumab
RationaleBiologics are becoming increasingly important in the management of severe asthma. However, little is known about the systemic immunometabolic consequences of Th2 response blockage.ObjectivesTo provide a better immunometabolic understanding of the effects of mepolizumab and omalizumab treatments by identifying potential biomarkers for monitoring.MethodsIn this exploratory longitudinal study severe asthmatic patients were followed for 18 months after initiating mepolizumab (n = 36) or Omalizumab (n = 20) treatment. Serum samples were collected before, 6, and 18 months after treatment. Targeted omic approaches were performed to analyze inflammatory metabolites (n = 35) and proteins (n = 45). 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.Measurements and Main ResultsMepolizumab 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 months and significantly correlate with clinical improvement. However, no significant biomolecules and no discriminative multivariate ROC curves were found for Omalizumab treatment.ConclusionsOur 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.
期刊介绍:
Allergy is an international and multidisciplinary journal that aims to advance, impact, and communicate all aspects of the discipline of Allergy/Immunology. It publishes original articles, reviews, position papers, guidelines, editorials, news and commentaries, letters to the editors, and correspondences. The journal accepts articles based on their scientific merit and quality.
Allergy seeks to maintain contact between basic and clinical Allergy/Immunology and encourages contributions from contributors and readers from all countries. In addition to its publication, Allergy also provides abstracting and indexing information. Some of the databases that include Allergy abstracts are Abstracts on Hygiene & Communicable Disease, Academic Search Alumni Edition, AgBiotech News & Information, AGRICOLA Database, Biological Abstracts, PubMed Dietary Supplement Subset, and Global Health, among others.