Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea.
Department of Critical Care Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Sci Rep. 2021 Oct 13;11(1):20300. doi: 10.1038/s41598-021-99777-w.
CD63 is one of the tetraspanin protein family members that is ubiquitously expressed on exosomes and is involved in the signal transduction of various types of immune cells. It may thus contribute to immunometabolic mechanisms of cellular and organ dysfunction in sepsis. Nonetheless, the association of exosomal CD63 with the severity and mortality of sepsis is not well known. Therefore, in the present study, the overall levels of exosomal CD63 were evaluated to ascertain whether they were associated with organ failure and mortality in patients with sepsis. Exosomal CD63 was measured from prospectively enrolled critically-ill patients with sepsis (n = 217) and healthy control (n = 20). To detect and quantify exosomes in plasma, a commercially available enzyme-linked immunosorbent assay kit was used according to the manufacturer's protocol. The total number of exosomal CD63 was determined by quantifying the immunoreactive CD63. The association between plasma levels of exosomal CD63 and sequential organ failure assessment (SOFA) score was assessed by a linear regression method. The best cut-off level of exosomal CD63 for 28-day mortality prediction was determined by Youden's index. Among 217 patients with sepsis, 143 (66%) patients were diagnosed with septic shock. Trends of increased exosomal CD63 levels were observed in control, sepsis, and septic-shock groups (6.6 µg/mL vs. 42 µg/mL vs. 90 µg/mL, p < 0.001). A positive correlation between exosomal CD63 and SOFA scores was observed in patients with sepsis (r value = 0.35). When patients were divided into two groups according to the best cut-off level, the group with higher exosomal CD63 levels (more than 126 µg/mL) was significantly associated with 28-day and in-hospital mortality. Moreover, the Kaplan-Meier survival method showed a significant difference in 90-day survival between patients with high- and low-exosomal CD63 levels (log-rank p = 0.005). Elevated levels of exosomal CD63 were associated with the severity of organ failure and predictive of mortality in critically ill patients with sepsis.
CD63 是四跨膜蛋白家族成员之一，广泛表达于外泌体上，并参与各种类型免疫细胞的信号转导。因此，它可能有助于脓毒症中细胞和器官功能障碍的免疫代谢机制。然而，外泌体 CD63 与脓毒症严重程度和死亡率的关联尚不清楚。因此，在本研究中，评估了外泌体 CD63 的总水平，以确定其是否与脓毒症患者的器官衰竭和死亡率相关。从前瞻性纳入的脓毒症（n=217）和健康对照（n=20）的危重症患者中测量外泌体 CD63。使用商业上可获得的酶联免疫吸附测定试剂盒，根据制造商的方案检测和定量血浆中的外泌体。通过定量免疫反应性 CD63 来确定外泌体 CD63 的总数。通过线性回归方法评估血浆中外泌体 CD63 水平与序贯器官衰竭评估（SOFA）评分之间的关联。通过 Youden 指数确定外泌体 CD63 预测 28 天死亡率的最佳截断值。在 217 例脓毒症患者中，143 例（66%）患者被诊断为感染性休克。在对照组、脓毒症组和感染性休克组中观察到外泌体 CD63 水平升高的趋势（6.6μg/mL 比 42μg/mL 比 90μg/mL，p<0.001）。在脓毒症患者中观察到外泌体 CD63 与 SOFA 评分之间存在正相关（r 值=0.35）。当根据最佳截断值将患者分为两组时，外泌体 CD63 水平较高（超过 126μg/mL）的组与 28 天和住院死亡率显著相关。此外，Kaplan-Meier 生存法显示高外泌体 CD63 水平和低外泌体 CD63 水平患者 90 天生存率之间存在显著差异（对数秩 p=0.005）。外泌体 CD63 水平升高与器官衰竭的严重程度相关，并可预测脓毒症危重症患者的死亡率。
