Sepsis is a heterogeneous syndrome clinically and biologically but biomarkers of distinct host response pathways for early prognostic information and testing targeted treatments are lacking. We hypothesized that Olfactomedin 4 (OLFM4), a matrix glycoprotein of neutrophil specific granules defines a distinct neutrophil subset that may be an independent risk factor for poor outcomes in sepsis. In a single-center, prospective cohort study, we enrolled adults admitted to an academic medical center from the Emergency Department (ED) with suspected sepsis (identified by 2 or greater Systemic Inflammatory Response Syndrome [SIRS] criteria and antibiotic receipt) from March 2016 through December 2017, followed by sepsis adjudication according to Sepsis-3. We collected 200mL of whole blood within 24 hours of admission and stained for the neutrophil surface marker CD66b followed by intracellular staining for OLFM4 quantitated by flow cytometry. The predictor for 60-day mortality was the percentage of OLFM4+ neutrophils and at a cut-point of OLFM4+ ≥37.6% determined by the Youden Index. Of 120 enrolled patients with suspected sepsis, 97 had sepsis and 23 had non-sepsis SIRS. The mean percentage of OLFM4+ neutrophils was significantly increased in both sepsis and non-sepsis SIRS patients who died (P ≤ 0.01). Among sepsis patients with elevated OLFM4+(≥37.6%), 56% died compared to 18% with OLFM4+ <37.6% (P=0.001).The association between OLFM4+ and mortality withstood adjustment for demographics, co-morbidities and measures of severity of illness (P<0.03). In sepsis, OLFM4+ neutrophil percentage is independently associated with 60-day mortality and may represent a novel measure of the heterogeneity of host response to sepsis.

中文翻译：

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由细胞内嗅觉蛋白 4 定义的中性粒细胞亚群与败血症中的死亡率相关

脓毒症在临床和生物学上是一种异质综合征，但缺乏用于早期预后信息和测试靶向治疗的不同宿主反应途径的生物标志物。我们假设中性粒细胞特异性颗粒的基质糖蛋白 Olfactomedin 4 (OLFM4) 定义了一个独特的中性粒细胞亚群，这可能是败血症预后不良的独立危险因素。在一项单中心、前瞻性队列研究中，我们招募了自 2016 年 3 月起从急诊科 (ED) 进入学术医疗中心的疑似败血症（通过 2 项或更多系统性炎症反应综合征 [SIRS] 标准和抗生素治疗确定）的成年人到 2017 年 12 月，然后根据 Sepsis-3 进行败血症裁决。我们在入院后 24 小时内收集了 200 mL 全血，并对中性粒细胞表面标志物 CD66b 进行染色，然后通过流式细胞术对 OLFM4 进行细胞内染色。60 天死亡率的预测因子是 OLFM4+ 中性粒细胞的百分比，并且在 OLFM4+ ≥37.6% 的切点处由 Youden 指数确定。在 120 名疑似脓毒症患者中，97 人患有脓毒症，23 人患有非脓毒症 SIRS。死亡的脓毒症和非脓毒症 SIRS 患者 OLFM4+ 中性粒细胞的平均百分比显着增加（P ≤ 0.01）。在 OLFM4+ 升高（≥37.6%）的脓毒症患者中，56% 死亡，而 OLFM4+ <37.6% 为 18%（P=0.001）。OLFM4+ 与死亡率之间的关联经受住了人口统计学、合并症和疾病严重程度测量的调整(P<0.03)。在脓毒症中，