Laboratory of Molecular Medicine, Department of Clinical Immunology, Rigshospitalet, Copenhagen University Hospital, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
PLoS One. 2013 Sep 9;8(9):e73119. doi: 10.1371/journal.pone.0073119. eCollection 2013.
The long pentraxin-3 (PTX3) is a key component of the humoral arm of the innate immune system. PTX3 is produced locally in response to pro-inflammatory stimuli. To investigate PTX3 levels and its use as a biomarker in patients with systemic inflammation, we developed a solid-phase enzyme-linked immunosorbent assay based on novel anti-PTX3 monoclonal antibodies detecting PTX3 with high sensitivity. The assay was applied on 261 consecutive patients admitted to an intensive care unit prospectively monitored with the systemic inflammatory response syndrome (SIRS). 100 blood donors were included as controls. PTX3 levels were elevated in patients (median = 71.3 ng/ml) compared with the controls (median = 0 ng/ml) (Mann-Whitney, p<0.0001). ROC analysis showed that PTX3 levels were significantly specific (85.0%) and sensitive (89.1%) to discriminate between healthy controls and patients (area under the curve (AUC) 0.922 (95% CI 0.892 to 0.946, p<0.0001)). Higher levels of PTX3 were associated with the development of sepsis, severe sepsis and septic shock (p = 0.0001). The serum levels of PTX3 correlated significantly with SAPS2 score (Spearman's rho 0.28, p<0.0001). Patients with high levels of PTX3 at admission did have a higher 90 day mortality rate than patients with the 25% lowest levels (Cox regression analysis, hazard ratio 3.0, p = 0.0009). In conclusion, we have established a highly sensitive and robust assay for measurement of PTX3 and found that its serum concentrations correlated with disease severity and mortality in patients with SIRS and sepsis.
长 pentraxin-3 (PTX3) 是先天免疫系统体液免疫的关键组成部分。PTX3 是局部产生的，以响应促炎刺激。为了研究全身炎症患者的 PTX3 水平及其作为生物标志物的作用，我们开发了一种基于新型抗-PTX3 单克隆抗体的固相酶联免疫吸附测定法，该方法具有高灵敏度。该测定法应用于 261 例连续入院的重症监护病房患者，前瞻性监测全身炎症反应综合征 (SIRS)。100 名献血者作为对照。与对照组 (中位数=0ng/ml) 相比，患者的 PTX3 水平升高 (中位数=71.3ng/ml) (Mann-Whitney，p<0.0001)。ROC 分析显示，PTX3 水平对区分健康对照者和患者具有显著的特异性 (85.0%) 和敏感性 (89.1%) (曲线下面积 (AUC) 0.922(95%CI 0.892 至 0.946，p<0.0001))。较高的 PTX3 水平与脓毒症、严重脓毒症和脓毒性休克的发生相关 (p=0.0001)。PTX3 血清水平与 SAPS2 评分显著相关 (Spearman's rho 0.28，p<0.0001)。入院时 PTX3 水平较高的患者 90 天死亡率确实高于 PTX3 水平最低的 25%患者 (Cox 回归分析，风险比 3.0，p=0.0009)。总之，我们建立了一种高度敏感和稳健的测定法来测量 PTX3，发现其血清浓度与 SIRS 和脓毒症患者的疾病严重程度和死亡率相关。
