Parthasarathy Upasana, Kuang Yi, Thakur Gunjan, Hogan John D, Wyche Thomas P, Norton James E, Killough Jason R, Sana Theodore R, Beakes Caroline, Shyong BaoJen, Zhang Rena N, Gutierrez Dario A, Filbin Michael, Christiani David C, Therien Alex G, Woelk Christopher H, White Cory H, Martinelli Roberta
Discovery Immunology, Merck & Co.,Inc., Cambridge, MA, USA.
Data and Genome Sciences, Merck & Co.,Inc., Cambridge, MA, USA.
iScience. 2023 Jan 7;26(2):105948. doi: 10.1016/j.isci.2023.105948. eCollection 2023 Feb 17.
Sepsis is a life-threatening condition caused by a dysregulated host response to infection. Despite continued efforts to understand the pathophysiology of sepsis, no effective therapies are currently available. While singular components of the aberrant immune response have been investigated, comprehensive studies linking different data layers are lacking. Using an integrated systems immunology approach, we evaluated neutrophil phenotypes and concomitant changes in cytokines and metabolites in patients with sepsis. Our findings identify differentially expressed mature and immature neutrophil subsets in patients with sepsis. These subsets correlate with various proteins, metabolites, and lipids, including pentraxin-3, angiopoietin-2, and lysophosphatidylcholines, in patients with sepsis. These results enabled the construction of a statistical model based on weighted multi-omics linear regression analysis for sepsis biomarker identification. These findings could help inform early patient stratification and treatment options, and facilitate further mechanistic studies targeting the trifecta of surface marker expression, cytokines, and metabolites.
脓毒症是一种由宿主对感染的失调反应引起的危及生命的病症。尽管一直在努力了解脓毒症的病理生理学，但目前尚无有效的治疗方法。虽然已经对异常免疫反应的单个成分进行了研究，但缺乏将不同数据层联系起来的全面研究。我们采用综合系统免疫学方法，评估了脓毒症患者的中性粒细胞表型以及细胞因子和代谢产物的伴随变化。我们的研究结果确定了脓毒症患者中差异表达的成熟和未成熟中性粒细胞亚群。这些亚群与脓毒症患者的各种蛋白质、代谢产物和脂质相关，包括五聚体蛋白-3、血管生成素-2和溶血磷脂酰胆碱。这些结果使得能够基于加权多组学线性回归分析构建一个用于脓毒症生物标志物识别的统计模型。这些发现有助于为早期患者分层和治疗选择提供信息，并促进针对表面标志物表达、细胞因子和代谢产物三者关系的进一步机制研究。
