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.

中文翻译：

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用于监测用美泊利单抗或奥马珠单抗治疗的严重哮喘的多组学整合分析


RationaleBiologics 在严重哮喘的管理中变得越来越重要。然而，人们对 Th2 反应阻断的全身免疫代谢后果知之甚少。目的通过确定用于监测的潜在生物标志物，更好地了解美泊利单抗和奥马珠单抗治疗的效果。方法在这项探索性纵向研究中，在开始美泊利单抗 （n = 36） 或奥马珠单抗 （n = 20） 治疗后，对严重哮喘患者进行了 18 个月的随访。在治疗前、治疗后 6 个月和 18 个月收集血清样本。采用靶向组学方法分析炎症代谢物 （n = 35） 和蛋白质 （n = 45）。对每种治疗单独进行多组学整合，应用监督分析使用 Latent cOmPonents （DIABLO） 框架进行数据整合分析以发现生物标志物。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。测量和主要结果美泊利单抗和奥马珠单抗都是有效的 （改善的临床变量），并且在治疗期间对严重哮喘患者表现出不同和特异性的代谢和蛋白质谱。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，这可以解释美泊利单抗治疗在 18 个月内观察到的差异，并与临床改善显着相关。然而，没有发现用于 Omalizumab 治疗的显着生物分子和判别性的多变量 ROC 曲线。结论我们的结果为美泊利单抗和奥马珠单抗对严重哮喘炎症反应免疫代谢动力学的不同影响提供了全面的见解。我们确定了一组具有监测美泊利单抗治疗潜力的生物分子，这些生物分子可能有助于个性化医疗。