A specific calprotectin neo-epitope (CPa9-HNE) in serum from inflammatory bowel disease patients is associated with neutrophil activity and endoscopic severity

Mortensen, J. H. et al. (2022) A specific calprotectin neo-epitope (CPa9-HNE) in serum from inflammatory bowel disease patients is associated with neutrophil activity and endoscopic severity. Journal of Crohn's and Colitis, 16(9), pp. 1447-1460. (doi: 10.1093/ecco-jcc/jjac047) (PMID:35304895) (PMCID:PMC9455793)

Abstract

Background and aims: Endoscopy and the use of fecal calprotectin (fecal CP) are among the least favored methods for assessing disease activity by inflammatory bowel disease (IBD) patients; the handling/processing of fecal samples is also impractical. Therefore, we sought to develop a novel neo-epitope serum calprotectin ELISA, CPa9-HNE, with the aim of quantifying neutrophil activity and NETosis and proposing a non-invasive method for monitoring disease activity in IBD patients. Methods: In vitro cleavage was performed by mixing calprotectin (S100A9/S100A8) with human neutrophil elastase (HNE), and a novel HNE-derived calprotectin neo-epitope (CPa9-HNE) was identified by mass spectrometry for ELISA development. The CPa9-HNE ELISA was quantified in supernatants from ex vivo activated neutrophils and serum samples from patients with ulcerative colitis (UC, n = 43), Crohn’s disease (CD, n = 93), and healthy subjects (HS, n = 23). For comparison, fecal CP and MRP8/14 biomarkers were also measured. Results: CPa9-HNE was specific for activated neutrophils ex vivo. Serum CPa9-HNE levels were four fold higher in CD (p<0.0001) and UC (p<0.0001) patients than in HS. CPa9-HNE correlated well with the SES-CD score (r=0.61, p<0.0001), MES (r=0.46, p=0.0141), and the full Mayo score (r=0.52, p=0.0013). CPa9-HNE was able to differentiate between CD and UC patients in endoscopic remission and moderate/severe disease activity (CD: AUC=0.82 (p=0.0003), UC: AUC=0.87 (p=0.0004). The performance of CPa9-HNE was equipotent or slightly better than that of fecal CP. Conclusion: Serum CPa9-HNE levels were highly associated with CD and UC patients. CPa9-HNE correlated with the SES-CD score and the full Mayo score, indicating a strong association with disease activity.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McCall, Kathryn and Goodyear, Professor Carl
• Authors: Mortensen, J. H., Sinkeviciute, D., Manon-Jensen, T., Domislović, V., McCall, K., Thudium, C. S., Brinar, M., Önnerfjord, P., Goodyear, C. S., Krznarić, Ž., Karsdal, M. A., and Bay-Jensen, A.-C.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Research Centre: College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology
• Journal Name: Journal of Crohn's and Colitis
• Publisher: Oxford University Press
• ISSN: 1873-9946
• ISSN (Online): 1876-4479
• Published Online: 19 March 2022
• Copyright Holders: Copyright © 2022 The Authors
• First Published: First published in Journal of Crohn's and Colitis 16(9): 1447-1460
• Publisher Policy: Reproduced under a Creative Commons License