Department of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala, Sweden; Diagnostics Development a P&M Venge AB company, Uppsala, Sweden.
Diagnostics Development a P&M Venge AB company, Uppsala, Sweden.
J Immunol Methods. 2019 Nov;474:112627. doi: 10.1016/j.jim.2019.06.018. Epub 2019 Jun 23.
The distinction between bacterial and viral causes of acute infections is a major clinical challenge. In this report we investigate the diagnostic performance in this regard of nine candidate biomarkers together with HNL (Human Neutrophil Lipocalin).
Blood was obtained from patients with symptoms of infectious (n = 581). HNL was measured in whole blood (B-HNL) after pre-activation with the neutrophil activator fMLP or in plasma (P-HNL). Azurocidin also known as heparin-binding protein (HBP), Calprotectin, PMN-CD64, CRP (C-reactive protein), IP-10 (Interferon γ-induced Protein 10 kDa), PCT (Procalcitonin), TK1 (Thymidine kinase 1), TRAIL (TNF-related apoptosis-inducing ligand) were measured in plasma/serum. Area under the ROC (receiver operating characteristics) curve (AuROC) was used for the evaluation of the clinical performance of the biomarkers.
Side-by-side comparisons of the ten biomarkers showed large difference in the AuROC with B-HNL being the superior biomarker (0.91, 95% CI 0.86-0.95) and with the other nine biomarkers varying from AuROC of 0.63-0.79. The combination of B-HNL with IP-10 and/or TRAIL increased the diagnostic performance further to AuROCs of 0.94-0.97. The AuROCs of the combination of CRP with IP-10 and/or TRAIL were significantly lower than combinations with B-HNL 0.87 (95% CI 0.83-0.91).
The diagnostic performance of whole blood activated HNL was superior in the distinction between bacterial or viral infections. The addition of IP-10 and/or TRAIL to the diagnostic algorithm increased the performance of B-HNL further. The rapid analysis of HNL, reflecting bacterial infections, together with biomarkers reflecting viral infections may be the ideal combination of diagnostic biomarkers of acute infections.
区分急性感染的细菌和病毒病因是一项重大的临床挑战。在本报告中，我们研究了九种候选生物标志物与 HNL（人中性粒细胞脂钙蛋白）在这方面的诊断性能。
从有感染症状的患者（n=581）中采集血液。用中性粒细胞激活剂 fMLP 预激活后在全血（B-HNL）中或在血浆（P-HNL）中测量 HNL。同时还测量了天青杀素（也称为肝素结合蛋白（HBP））、钙卫蛋白、PMN-CD64、C 反应蛋白（CRP）、IP-10（干扰素 γ 诱导的蛋白 10 kDa）、降钙素原（PCT）、胸苷激酶 1（TK1）、TRAIL（TNF 相关凋亡诱导配体）在血浆/血清中的含量。ROC（接收者操作特性）曲线下面积（AuROC）用于评估生物标志物的临床性能。
十种生物标志物的并排比较显示，B-HNL 的 AuROC 具有优势（0.91，95%CI 0.86-0.95），而其他九种生物标志物的 AuROC 从 0.63-0.79 不等。B-HNL 与 IP-10 和/或 TRAIL 的组合进一步提高了诊断性能，达到了 0.94-0.97 的 AuROC。CRP 与 IP-10 和/或 TRAIL 的组合的 AuROC 明显低于与 B-HNL 的组合（0.87，95%CI 0.83-0.91）。
全血激活 HNL 在区分细菌或病毒感染方面的诊断性能更优。将 IP-10 和/或 TRAIL 添加到诊断算法中进一步提高了 B-HNL 的性能。快速分析反映细菌感染的 HNL 与反映病毒感染的生物标志物的结合可能是急性感染诊断生物标志物的理想组合。
