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A Specific Calprotectin Neo-epitope [CPa9-HNE] in Serum from Inflammatory Bowel Disease Patients Is Associated with Neutrophil Activity and Endoscopic Severity

Mortensen, Joachim Høg ; Sinkeviciute, Dovile LU ; Manon-Jensen, Tina ; Domislović, Viktor ; McCall, Kathryn ; Thudium, Christian S. LU ; Brinar, Marko ; Önnerfjord, Patrik LU orcid ; Goodyear, Carl S. and Krznarić, Željko , et al. (2022) In Journal of Crohn's & Colitis 16(9). p.1447-1460
Abstract

BACKGROUND AND AIMS: Endoscopy and the use of faecal calprotectin [faecal CP] are among the least-favoured methods for assessing disease activity by inflammatory bowel disease [IBD] patients; the handling/processing of faecal samples is also impractical. Therefore, we sought to develop a novel neo-epitope serum calprotectin enzyme-linked immunosorbent assay [ELISA], CPa9-HNE, with the aim of quantifying neutrophil activity and neutrophil extracellular trap [NET]-osis 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... (More)

BACKGROUND AND AIMS: Endoscopy and the use of faecal calprotectin [faecal CP] are among the least-favoured methods for assessing disease activity by inflammatory bowel disease [IBD] patients; the handling/processing of faecal samples is also impractical. Therefore, we sought to develop a novel neo-epitope serum calprotectin enzyme-linked immunosorbent assay [ELISA], CPa9-HNE, with the aim of quantifying neutrophil activity and neutrophil extracellular trap [NET]-osis 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, faecal CP and MRP8/14 biomarkers were also measured. RESULTS: CPa9-HNE was specific for activated neutrophils ex vivo. Serum CPa9-HNE levels were 4-fold higher in CD [p <0.0001] and UC [p <0.0001] patients than in HS. CPa9-HNE correlated well with the Simple Endoscopic Score [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: area under the curve [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 faecal CP. CONCLUSIONS: 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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
biomarkers, Calprotectin, IBD, inflammation, neutrophil elastase, neutrophil extracellular traps [NETs], neutrophil granulocyte
in
Journal of Crohn's & Colitis
volume
16
issue
9
pages
14 pages
publisher
Oxford University Press
external identifiers
  • scopus:85137104421
  • pmid:35304895
ISSN
1873-9946
DOI
10.1093/ecco-jcc/jjac047
language
English
LU publication?
yes
id
731d5a69-e188-4460-811c-0f3b57a1efc7
date added to LUP
2022-12-29 10:22:07
date last changed
2024-06-15 01:13:27
@article{731d5a69-e188-4460-811c-0f3b57a1efc7,
  abstract     = {{<p>BACKGROUND AND AIMS: Endoscopy and the use of faecal calprotectin [faecal CP] are among the least-favoured methods for assessing disease activity by inflammatory bowel disease [IBD] patients; the handling/processing of faecal samples is also impractical. Therefore, we sought to develop a novel neo-epitope serum calprotectin enzyme-linked immunosorbent assay [ELISA], CPa9-HNE, with the aim of quantifying neutrophil activity and neutrophil extracellular trap [NET]-osis 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, faecal CP and MRP8/14 biomarkers were also measured. RESULTS: CPa9-HNE was specific for activated neutrophils ex vivo. Serum CPa9-HNE levels were 4-fold higher in CD [p &lt;0.0001] and UC [p &lt;0.0001] patients than in HS. CPa9-HNE correlated well with the Simple Endoscopic Score [SES]-CD score [r = 0.61, p &lt;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: area under the curve [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 faecal CP. CONCLUSIONS: 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.</p>}},
  author       = {{Mortensen, Joachim Høg and Sinkeviciute, Dovile and Manon-Jensen, Tina and Domislović, Viktor and McCall, Kathryn and Thudium, Christian S. and Brinar, Marko and Önnerfjord, Patrik and Goodyear, Carl S. and Krznarić, Željko and Karsdal, Morten Asser and Bay-Jensen, Anne Christine}},
  issn         = {{1873-9946}},
  keywords     = {{biomarkers; Calprotectin; IBD; inflammation; neutrophil elastase; neutrophil extracellular traps [NETs]; neutrophil granulocyte}},
  language     = {{eng}},
  number       = {{9}},
  pages        = {{1447--1460}},
  publisher    = {{Oxford University Press}},
  series       = {{Journal of Crohn's & Colitis}},
  title        = {{A Specific Calprotectin Neo-epitope [CPa9-HNE] in Serum from Inflammatory Bowel Disease Patients Is Associated with Neutrophil Activity and Endoscopic Severity}},
  url          = {{http://dx.doi.org/10.1093/ecco-jcc/jjac047}},
  doi          = {{10.1093/ecco-jcc/jjac047}},
  volume       = {{16}},
  year         = {{2022}},
}