Kapp Kathryn L, Arul Albert B, Zhang Kevin C, Du Liping, Yende Sachin, Kellum John A, Angus Derek C, Peck-Palmer Octavia M, Robinson Renã A S
Department of Chemistry, Vanderbilt University, 5423 Stevenson Center, Nashville, TN, 37235, USA.
The Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, TN, 32732, USA.
Mol Omics. 2022 Dec 5;18(10):923-937. doi: 10.1039/d2mo00171c.
Intra-abdominal infection is a common cause of sepsis, and intra-abdominal sepsis leads to ∼156 000 U.S. deaths annually. African American/Black adults have higher incidence and mortality rates from sepsis compared to Non-Hispanic White adults. A limited number of studies have traced survival outcomes to molecular changes; however, these studies primarily only included Non-Hispanic White adults. Our goal is to better understand molecular changes that may contribute to differences in sepsis survival in African American/Black and Non-Hispanic White adults with primary intra-abdominal infection. We employed discovery-based plasma proteomics of patient samples from the Protocolized Care for Early Septic Shock (ProCESS) cohort ( = 107). We identified 49 proteins involved in the acute phase response and complement system whose expression levels are associated with both survival outcome and racial background. Additionally, 82 proteins differentially-expressed in survivors were specific to African American/Black or Non-Hispanic White patients, suggesting molecular-level heterogeneity in sepsis patients in key inflammatory pathways. A smaller, robust set of 19 proteins were in common in African American/Black and Non-Hispanic White survivors and may represent potential universal molecular changes in sepsis. Overall, this study identifies molecular factors that may contribute to differences in survival outcomes in African American/Black patients that are not fully explained by socioeconomic or other non-biological factors.
腹腔内感染是脓毒症的常见病因,腹腔内脓毒症每年导致约15.6万美国人死亡。与非西班牙裔白人成年人相比,非裔美国/黑人成年人脓毒症的发病率和死亡率更高。仅有少数研究将生存结果追溯至分子变化;然而,这些研究主要仅纳入了非西班牙裔白人成年人。我们的目标是更好地了解可能导致原发性腹腔内感染的非裔美国/黑人与非西班牙裔白人成年人脓毒症生存差异的分子变化。我们采用基于发现的血浆蛋白质组学方法,对早期脓毒性休克规范化治疗(ProCESS)队列中的患者样本(n = 107)进行了研究。我们鉴定出49种参与急性期反应和补体系统的蛋白质,其表达水平与生存结果和种族背景均相关。此外,82种在幸存者中差异表达的蛋白质分别是非裔美国/黑人或非西班牙裔白人患者所特有的,这表明脓毒症患者在关键炎症途径中存在分子水平的异质性。一组规模较小但可靠的19种蛋白质在非裔美国/黑人和非西班牙裔白人幸存者中是共有的,可能代表了脓毒症中潜在的普遍分子变化。总体而言,本研究确定了一些分子因素,这些因素可能导致非裔美国/黑人患者的生存结果差异,而社会经济或其他非生物学因素并不能完全解释这些差异。