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

IF 12.6 1区 医学 Q1 ALLERGY
Allergy Pub Date : 2024-12-18 DOI:10.1111/all.16434
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
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引用次数: 0

摘要

在严重哮喘的治疗中,rationalbiologics正变得越来越重要。然而,对Th2反应阻断的全身免疫代谢后果知之甚少。目的通过识别潜在的生物标志物进行监测,更好地了解mepolizumab和omalizumab治疗的免疫代谢作用。方法在这项探索性的纵向研究中,重症哮喘患者在开始mepolizumab (n = 36)或Omalizumab (n = 20)治疗后随访18个月。分别于治疗前、治疗后6个月和18个月采集血清样本。采用靶向组学方法分析炎症代谢物(n = 35)和蛋白质(n = 45)。使用潜在成分(DIABLO)框架进行生物标志物发现的数据集成分析,对每个治疗分别进行多组学整合。然后,使用多变量ROC分析确认潜在的生物标志物,并与治疗过程中的临床变量相关。mepolizumab和omalizumab在重度哮喘患者治疗期间均有效(改善临床变量),并显示出不同的特异性代谢和蛋白质谱。多组学整合和多变量ROC分析确定了特定的生物标志物,如花生四烯酸、棕榈油酸、油酸、丙酰肉碱、胆红素、CCL11和TNFSF10,这些标志物可以解释Mepolizumab治疗18个月后观察到的差异,并与临床改善显著相关。然而,没有发现Omalizumab治疗的显著生物分子和判别性多变量ROC曲线。结论我们的研究结果全面揭示了美泊珠单抗和奥玛珠单抗对严重哮喘患者炎症反应免疫代谢动力学的差异作用。我们确定了一组具有监测mepolizumab治疗潜力的生物分子,这可能对个性化医疗有用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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.
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来源期刊
Allergy
Allergy 医学-过敏
CiteScore
26.10
自引率
9.70%
发文量
393
审稿时长
2 months
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.
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