Hansen Annika Hummersgaard, Mortensen Joachim Høg, Rønnow Sarah Rank, Karsdal Morten Asser, Leeming Diana Julie, Sand Jannie Marie Bülow
Nordic Bioscience, 2730 Herlev, Denmark.
J Clin Med. 2023 Dec 8;12(24):7589. doi: 10.3390/jcm12247589.
Neutrophil activation can release neutrophil extracellular traps (NETs) in acute inflammation. NETs result in the release of human neutrophil elastase (HNE) and calprotectin, where the former can degrade the latter and generate protein fragments associated with neutrophil activity. We investigated this in chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) using the novel neoepitope biomarker CPa9-HNE, quantifying a specific HNE-mediated fragment of calprotectin in serum. CPa9-HNE was compared to total calprotectin. Initially, CPa9-HNE was measured in healthy ( 39), COPD ( 67), and IPF ( 16) serum using a neoepitope-specific competitive enzyme-linked immunosorbent assay. Then, a head-to-head comparison of CPa9-HNE and total calprotectin, a non-neoepitope, was conducted in healthy ( 19), COPD ( 25), and IPF ( 19) participants. CPa9-HNE levels were significantly increased in COPD ( 0.0001) and IPF subjects ( = 0.0001) when compared to healthy participants. Additionally, CPa9-HNE distinguished IPF ( 0.0001) and COPD ( 0.0001) from healthy participants more effectively than total calprotectin for IPF ( = 0.0051) and COPD ( = 0.0069). Here, CPa9-HNE also distinguished IPF from COPD ( = 0.045) participants, which was not observed for total calprotectin ( = 0.98). Neutrophil activity was significantly higher, as assessed via serum CPa9-HNE, for COPD and IPF compared to healthy participants. Additionally, CPa9-HNE exceeded the ability of non-neoepitope calprotectin serum measurements to separate healthy from lung disease and even COPD from IPF participants, indicating that neutrophil activity is essential for both COPD and IPF.
在急性炎症中，中性粒细胞激活可释放中性粒细胞胞外诱捕网（NETs）。NETs会导致人中性粒细胞弹性蛋白酶（HNE）和钙卫蛋白的释放，其中前者可降解后者并生成与中性粒细胞活性相关的蛋白质片段。我们使用新型新表位生物标志物CPa9 - HNE，通过量化血清中钙卫蛋白的特定HNE介导片段，在慢性阻塞性肺疾病（COPD）和特发性肺纤维化（IPF）中对此进行了研究。将CPa9 - HNE与总钙卫蛋白进行比较。最初，使用新表位特异性竞争酶联免疫吸附测定法在健康人（39例）、COPD患者（67例）和IPF患者（16例）的血清中测量CPa9 - HNE。然后，在健康人（19例）、COPD患者（25例）和IPF患者（19例）中对CPa9 - HNE和非新表位的总钙卫蛋白进行了直接比较。与健康参与者相比，COPD患者（P = 0.0001）和IPF患者（P = 0.0001）的CPa9 - HNE水平显著升高。此外，对于IPF（P = 0.0051）和COPD（P = 0.0069），CPa9 - HNE比总钙卫蛋白更有效地将IPF患者（P = 0.0001）和COPD患者（P = 0.0001）与健康参与者区分开来。在此，CPa9 - HNE也能区分IPF患者和COPD患者（P = 0.045），而总钙卫蛋白则未观察到这种区分能力（P = 0.98）。与健康参与者相比，通过血清CPa9 - HNE评估，COPD和IPF患者的中性粒细胞活性显著更高。此外，CPa9 - HNE在区分健康人与肺部疾病患者以及COPD患者与IPF患者方面超过了非新表位钙卫蛋白血清测量的能力，这表明中性粒细胞活性对COPD和IPF都至关重要。
