124 CPa9-HNE, A Novel Biomarker of Neutrophil Activity is Associated With Transmural Healing In Pediatric Crohn’s Disease
Bibliographic record
Abstract
Background: Infiltration of neutrophils into the intestinal tissue is a crucial component of the inflammatory response in Crohn‘s disease (CD). CPa9-HNE, a calprotectin fragment released by human neutrophil elastase during NETosis, has been shown to strongly correlate with endoscopic disease activity in adults with inflammatory bowel disease (IBD) and serves as an indicator for pharmacodynamic response. We aimed to investigate the association of CPa9-HNE with endoscopic disease activity and transmural healing in patients with pediatric CD. Methods: The cohort included 175 children with CD who underwent MRE and ileocolonoscopy as part of the ImageKids study (NCT01881490), with serum drawn at enrolment. Age and sex matched healthy subjects (HS) were included (n = 82). CPa9-HNE, a human neutrophil elastase-derived fragment of calprotectin, was measured in serum by ELISA. Endoscopic disease activity was graded using the SES-CD score and radiologic inflammation was assessed by MRE, using the radiologist global assessment (RGA) of inflammation recorded on a 0–100 mm visual analogue scale (VAS). Transmural healing was defined as endoscopic healing (SES-CD <3, EH) and RGA <10 mm. Spearman rho correlations and one-way ANOVA with Dunn‘s correction were applied. Results: CPa9-HNE showed a fair correlation to the SES-CD score (ρ = 0.30, P < 0.001). Positive correlation was also observed between CPa9-HNE and the RGA of inflammation (ρ = 0.30, P < 0.001). For SES-CD, CPa9-HNE was elevated in all subgroups compared with HS (P < 0.0001 for all) and demonstrated a step-wise increase across disease severity groups. Patients with severe endoscopic disease had significantly higher levels of CPa9-HNE than patients in remission (ng/ml [IQR]: 275.6 [182.4–461.9] vs 158.1 [127.6–211.2], P < 0.05). CPa9-HNE was able to discern patients with transmural healing from patients with transmural disease activity (ng/ml [IQR]: 154.8 [129.1–181.9] vs 250.6 [173.6–361.6], P < 0.001) (AUC [95% CI]: 0.77 [0.67–0.86]). Conclusions: This study shows that CPa9-HNE, a biomarker of neutrophil activity, is associated with mucosal and radiologic inflammation in pediatric CD. These findings highlight the potential use of CPa9-HNE as a complementary tool for endoscopic or radiographic assessment of intestinal inflammation, and provide an opportunity for further studies in children with CD.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".