Abstract Background Infiltration of neutrophils into 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 of 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 174 children with CD (aged 2-18 years, 56% male) 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 analog scale (VAS). Transmural healing was defined as endoscopic healing (SES-CD3, EH) and RGA10 mm. Spearman’s rho correlations and one-way ANOVA with Dunn’s correction were applied. Results CPa9-HNE showed a fair correlation with the SES-CD score (ρ = 0.30, p 0.001). A positive correlation was also observed between CPa9-HNE and RGA of inflammation (ρ = 0.30, p 0.001). For SES-CD, CPa9-HNE was significantly elevated in all subgroups compared with HS (p 0.0001 for all) and demonstrated a stepwise increase across disease severity groups (fig. 1A). Patients with severe endoscopic disease had significantly higher levels of CPa9-HNE than those in remission (ng/ml IQR: 275.6 182.4-461.9 vs. 158.1 127.6-211.2, p 0.05) (fig. 1A). CPa9-HNE was able to significantly discern patients with transmural healing from patients with transmural disease activity (fig. 1B) (AUC 95%CI: 0.77 0.67-0.86). Conclusion This study showed 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 the endoscopic or radiographic assessment of intestinal inflammation and provide an opportunity for further studies in children with CD. Conflict of interest: Dr. Mortensen, Joachim: Fulltime employee and shareholder at Nordic Bioscience A/S Focht, Gili: No conflict of interest Sorokina Alexdóttir, Marta: Fulltime employee at Nordic Bioscience A/S Quteineh, Ahmad: No conflict of interest Pehrsson, Martin: Fulltime employee at Nordic Bioscience A/S Griffiths, Anne: Grant: Abbvie Personal Fees: Abbvie, Alfasigma, Amgen, Janssen, Lilly, Merck, Pfizer, Roche, Takeda Church, Peter Christopher: No conflict of interest baldassano, Robert N.: No conflict of interest Silverstein, Jared: No conflict of interest Bay-Jensen, Anne-Christine: Fulltime employee and shareholder at Nordic Bioscience A/S Karsdal, Morten Asser: Fulltime employee and shareholder at Nordic Bioscience A/S Turner, Dan: Consultation fee: Janssen, Pfizer, Ferring, Abbvie, Takeda, Prometheus Biosciences, Lilly, SorrisoPharma, Boehringer Ingelheim, Galapagos, BMS, AlfaSigma, Merck, Gentech Research support: Janssen, Abbvie, Takeda, Pfizer Royalties: Shaare Zedek Medical Center, Hospital for Sick Children
Mortensen et al. (Thu,) studied this question.