140 CPa9-HNE and PRO-C6 Biomarkers Reflect Fibrostenotic Strictures and Endoscopic Disease Activity in Crohn’s Disease – IBSEN III Study
Bibliographic record
Abstract
Background: In Crohn’s disease (CD), persistent neutrophil activation, including neutrophil extracellular traps (NETs), together with fibroblast activation, contributes to pathological tissue remodeling. This interplay promotes excessive collagen deposition, mucosal damage, and ultimately fibrostenotic strictures. We investigated 2 serum biomarkers with distinct biological origins: PRO-C6, reflecting type VI collagen formation and myofibroblast activity, and a novel calprotectin neo-epitope (CPa9-HNE), indicative of neutrophil activation and NETosis. Their associations with endoscopic disease activity and fibrostenotic complications were assessed in treatment-naïve CD patients from the prospective IBSEN-III inception cohort. Methods: Serum from 142 patients with newly diagnosed CD was analyzed at baseline and after one year of follow-up. Disease phenotype was classified according to the Montreal system (luminal, fibrostenotic, fistulizing). The biomarkers (PRO-C6, CPa9-HNE)) were assayed at both time points (baseline: luminal n = 114, stricturing n = 23, fistulizing n = 5; year 1: luminal n = 111, stricturing n = 24, fistulizing n = 7). Cross-sectional analyses were paired with the corresponding Montreal classification, and longitudinal changes were evaluated. Statistical analyses included one-way ANOVA with LSD post-hoc testing. Results: Among the 2 markers, CPa9-HNE showed a significant correlation with endoscopic severity (SES-CD; r = 0.35, P = 0.009). At baseline, both PRO-C6 (P < 0.001) and CPa9-HNE (P < 0.05) were elevated in patients with stricturing disease compared to those with luminal CD. PRO-C6 remained elevated after one year in the stricturing group (P < 0.01). Notably, 9 patients initially classified as luminal CD developed strictures within one year; their baseline PRO-C6 levels were significantly higher than in patients who did not progress. Conclusions: These findings support PRO-C6 as a promising serum biomarker for intestinal fibrosis in Crohn’s disease, as it was elevated both at diagnosis and during follow-up in patients with strictures, and was able to identify patients at risk of progression. Elevated CPa9-HNE in stricturing disease further points to neutrophil activation and NETosis as drivers of fibrogenesis. Together, these serum biomarkers highlight complementary inflammatory and fibrotic pathways and may provide clinically useful tools for monitoring fibrostenotic complications in Crohn’s disease.
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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 | 0.000 | 0.000 |
| 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) | 0.001 | 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".