The CPa9-HNE biomarker provides a measure of true neutrophil activity by capturing the interplay between two specific key neutrophilic intracellular components; the antimicrobial protein calprotectin and the protease human neutrophil elastase (HNE).
Constant activation and recruitment of neutrophils is a common feature in IBD (Crohn’s disease and ulcerative colitis). Their infiltration into the intestinal tissue has been correlated to disease activity, where they induce mucosal damage through the release of neutrophil extracellular traps (NETosis). Therefore, measuring neutrophil activity using CPa9-HNE provides valuable insight into disease progression and inflammatory burden, potentially guiding the development and evaluation of novel therapeutic interventions, as further encouraged by the Letter of Support from the FDA.
Generation of the CPa9-HNE neo-epitopeNeutrophils travel toward the site of inflammation by migrating across the endothelium. Upon reaching the site of injury, neutrophils activate and undergo NETosis, releasing their intracellular components such as human neutrophil elastase (HNE) and CP. This leads to the generation of the CPa9-HNE neo-epitope in the extracellular space. Subsequently, upon tissue clearance, the fragment gets released into circulation, serving as a measure of neutrophil activity. Interested in CPa9-HNE? Reach out! |
CPa9-HNE measures true neutrophil activity |
 | The CPa9-HNE assay measures a specific calprotectin fragment, CPa9-HNE, that serves as a biomarker for activated neutrophils. While full-length calprotectin can be passively released by resting or inactive neutrophils, CPa9-HNE is released exclusively when neutrophils become activated, often in response to infection or inflammation. This specificity allows the assay to distinguish between baseline neutrophil presence and active inflammatory processes, making it a valuable tool for detecting active inflammation and monitoring immune response. |
CPa9-HNE provides added clinical value over measuring the full-length calprotectin protein alone. In patients achieving remission with the anti-TNF therapy adalimumab, levels of CPa9-HNE show a continuous reduction from baseline through week 52, reflecting a sustained decrease in neutrophil activation. This reduction serves as a marker of effective therapeutic response, offering insight into both the extent and duration of inflammation control in patients undergoing treatment. |  |
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The FDA endorses the CPa9-HNE assay for further investigation as a tool for clinical trials, where it can support multiple objectives, such as clinical trial enrichment, assessing the pharmacodynamic effects of immunomodulatory drugs, and monitoring treatment response.
For instance, CPa9-HNE strongly correlates with endoscopic disease activity. Furthermore, recent findings show that CPa9-HNE serves as an indicator for pharmacodynamic response, measuring the impact of the S1P modulator ozanimod on neutrophil activity – making it a valuable component for a comprehensive biomarker strategy, eventually improving patients’ quality of life.
The U.S. Food and Drug Administration (FDA) has issued a Letter of Support for further study of the CPa9-HNE biomarker assay in inflammatory bowel disease (IBD) studies. As per the Letter of Support, the FDA encourages the formal qualification of CPa9-HNE as an enrichment biomarker, recommending analytical validation and data sharing across clinical trials to advance its development as a drug development tool. The agency supports further study of CPa9-HNE to enable a non-invasive assessment of endoscopic disease activity in IBD patients. CPa9-HNE may improve clinical trials by identifying patients with moderate to severe active ulcerative colitis or Crohn’s disease, potentially reducing the need for unnecessary endoscopies. |
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