发热期可溶性尿激酶型纤溶酶原激活物受体和嗅鞘蛋白 4 作为成人重症登革热的预后生物标志物。

Febrile Phase Soluble Urokinase Plasminogen Activator Receptor and Olfactomedin 4 as Prognostic Biomarkers for Severe Dengue in Adults.

机构信息

Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.

Department of Medicine, The Doherty Institute, University of Melbourne, Melbourne, Australia.

出版信息

Clin Infect Dis. 2024 Mar 20;78(3):788-796. doi: 10.1093/cid/ciad637.

DOI:10.1093/cid/ciad637

PMID:37823481

Abstract

BACKGROUND

Dengue cases continue to rise and can overwhelm healthcare systems during outbreaks. In dengue, neutrophil mediators, soluble urokinase plasminogen activator receptor (suPAR) and olfactomedin 4, and mast cell mediators, chymase and tryptase, have not been measured longitudinally across the dengue phases. The utility of these proteins as prognostic biomarkers for severe dengue has also not been assessed in an older adult population.

METHODS

We prospectively enrolled 99 adults with dengue-40 dengue fever, 46 dengue with warning signs and 13 severe dengue, along with 30 controls. Plasma levels of suPAR, olfactomedin 4, chymase and tryptase were measured at the febrile, critical and recovery phases in dengue patients.

RESULTS

The suPAR levels were significantly elevated in severe dengue compared to the other dengue severities and controls in the febrile (P < .001), critical (P < .001), and recovery (P = .005) phases. In the febrile phase, suPAR was a prognostic biomarker of severe dengue, with an AUROC of 0.82. Using a cutoff derived from Youden's index (5.4 ng/mL) and an estimated prevalence of severe dengue (16.5%) in our healthcare institution, the sensitivity was 71.4% with a specificity of 87.9% in the febrile phase, and the positive and negative predictive values were 54.7% and 95.8%, respectively. Olfactomedin 4 was elevated in dengue patients but not in proportion to disease severity in the febrile phase (P = .04) There were no significant differences in chymase and tryptase levels between dengue patients and controls.

CONCLUSIONS

In adult dengue, suPAR may be a reliable prognostic biomarker for severe dengue in the febrile phase.

摘要

背景

登革热病例持续增加，在疫情爆发期间可能会使医疗系统不堪重负。在登革热中，中性粒细胞介质、可溶性尿激酶型纤溶酶原激活物受体（suPAR）和嗅觉素 4 以及肥大细胞介质糜蛋白酶和类胰蛋白酶尚未在登革热各阶段进行纵向测量。这些蛋白质作为老年人群中重症登革热的预后生物标志物的效用也尚未得到评估。

方法

我们前瞻性纳入了 99 例登革热 4 型患者，其中 40 例为登革热发热期，46 例为登革热预警期，13 例为重症登革热，同时纳入 30 例对照组。在登革热患者发热期、极期和恢复期测量 suPAR、嗅觉素 4、糜蛋白酶和类胰蛋白酶的血浆水平。

结果

与其他登革热严重程度和对照组相比，重症登革热患者的 suPAR 水平在发热期（P<0.001）、极期（P<0.001）和恢复期（P=0.005）均显著升高。在发热期，suPAR 是重症登革热的预后生物标志物，AUROC 为 0.82。使用 Youden 指数得出的截断值（5.4ng/mL）和我们医疗机构中重症登革热的估计患病率（16.5%），suPAR 在发热期的敏感性为 71.4%，特异性为 87.9%，阳性预测值为 54.7%，阴性预测值为 95.8%。嗅觉素 4 在登革热患者中升高，但在发热期与疾病严重程度不成比例（P=0.04）。糜蛋白酶和类胰蛋白酶水平在登革热患者和对照组之间无显著差异。