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Article

A Serological Neoepitope Biomarker of Neutrophil Elastase-Degraded Calprotectin, Associated with Neutrophil Activity, Identifies Idiopathic Pulmonary Fibrosis and Chronic Obstructive Pulmonary Disease More Effectively Than Total Calprotectin

by
Annika Hummersgaard Hansen
*,
Joachim Høg Mortensen
,
Sarah Rank Rønnow
,
Morten Asser Karsdal
,
Diana Julie Leeming
and
Jannie Marie Bülow Sand
Nordic Bioscience, 2730 Herlev, Denmark
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2023, 12(24), 7589; https://doi.org/10.3390/jcm12247589
Submission received: 3 October 2023 / Revised: 30 November 2023 / Accepted: 4 December 2023 / Published: 8 December 2023
(This article belongs to the Special Issue Biomarkers and Diagnostics in Respiratory Diseases)
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Abstract

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 (n = 39), COPD (n = 67), and IPF (n = 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 (n = 19), COPD (n = 25), and IPF (n = 19) participants. CPa9-HNE levels were significantly increased in COPD (p < 0.0001) and IPF subjects (p = 0.0001) when compared to healthy participants. Additionally, CPa9-HNE distinguished IPF (p < 0.0001) and COPD (p < 0.0001) from healthy participants more effectively than total calprotectin for IPF (p = 0.0051) and COPD (p = 0.0069). Here, CPa9-HNE also distinguished IPF from COPD (p = 0.045) participants, which was not observed for total calprotectin (p = 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.
Keywords: biomarker; neoepitope; neutrophil activity; IPF; COPD; calprotectin biomarker; neoepitope; neutrophil activity; IPF; COPD; calprotectin

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MDPI and ACS Style

Hansen, A.H.; Mortensen, J.H.; Rønnow, S.R.; Karsdal, M.A.; Leeming, D.J.; Sand, J.M.B. A Serological Neoepitope Biomarker of Neutrophil Elastase-Degraded Calprotectin, Associated with Neutrophil Activity, Identifies Idiopathic Pulmonary Fibrosis and Chronic Obstructive Pulmonary Disease More Effectively Than Total Calprotectin. J. Clin. Med. 2023, 12, 7589. https://doi.org/10.3390/jcm12247589

AMA Style

Hansen AH, Mortensen JH, Rønnow SR, Karsdal MA, Leeming DJ, Sand JMB. A Serological Neoepitope Biomarker of Neutrophil Elastase-Degraded Calprotectin, Associated with Neutrophil Activity, Identifies Idiopathic Pulmonary Fibrosis and Chronic Obstructive Pulmonary Disease More Effectively Than Total Calprotectin. Journal of Clinical Medicine. 2023; 12(24):7589. https://doi.org/10.3390/jcm12247589

Chicago/Turabian Style

Hansen, Annika Hummersgaard, Joachim Høg Mortensen, Sarah Rank Rønnow, Morten Asser Karsdal, Diana Julie Leeming, and Jannie Marie Bülow Sand. 2023. "A Serological Neoepitope Biomarker of Neutrophil Elastase-Degraded Calprotectin, Associated with Neutrophil Activity, Identifies Idiopathic Pulmonary Fibrosis and Chronic Obstructive Pulmonary Disease More Effectively Than Total Calprotectin" Journal of Clinical Medicine 12, no. 24: 7589. https://doi.org/10.3390/jcm12247589

APA Style

Hansen, A. H., Mortensen, J. H., Rønnow, S. R., Karsdal, M. A., Leeming, D. J., & Sand, J. M. B. (2023). A Serological Neoepitope Biomarker of Neutrophil Elastase-Degraded Calprotectin, Associated with Neutrophil Activity, Identifies Idiopathic Pulmonary Fibrosis and Chronic Obstructive Pulmonary Disease More Effectively Than Total Calprotectin. Journal of Clinical Medicine, 12(24), 7589. https://doi.org/10.3390/jcm12247589

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