Abstract Background Inflammatory bowel diseases (IBD) are chronic immune-mediated inflammatory disorders, mainly involving the gastrointestinal tract. Novel approaches to investigate the pathophysiology of these diseases include single-cell experiments and spatial transcriptomics. These techniques increasingly rely on high-quality mucosal tissue. However, standard forceps biopsies usually provide insufficient cellular yield, with low numbers of less abundant cell types.1,2 Cold-snare resection is a well-established technique used for endoscopic polypectomy. It yields larger and higher quality specimens, but its utility in IBD has not yet been evaluated.3 Cold-snare tissue collection in the duodenum was shown to be feasible and safe.3 The current study aims to assess the feasibility of cold-snare tissue collection in IBD, and to compare immune cell composition of the obtained tissue with biopsies collected with biopsy forceps, focussing on highly abundant immune cells such as T cells, and on rare immune cells such as the family of innate lymphoid cells (ILCs). Methods In this prospective study, patients with active IBD (CD: SES-CD≥3; UC: Mayo endoscopic sub score≥1), scheduled for ileocolonoscopy, were enrolled and consented. From an inflamed segment, one cold-snare resection and two forceps biopsies were obtained. Success rate, defined as a procedure resulting in the procurement of a cold-snare biopsy, was recorded. The biopsies from 7 patients were processed for flow cytometry to quantify cell viability and immune cell subsets. Adverse events (AEs) were recorded during a phone-call 7 days after the procedure and during a follow-up period of 30 days. Results 23 patients were included (12 CD, 11 UC). Biopsies were obtained from the rectum (n = 12), colon (n = 7), and terminal ileum (n = 4). The procedure success rate was 100%. Compared to two forceps biopsies, cold-snare specimens yielded a higher number of viable cells (mean ± SEM: 1.98 × 106 vs. 0.83 × 106; p.001, Welch’s t-test) and showed a higher viability after digestion (82.7% vs. 66.7%, p.05, paired t-test, figure 1A and B). In addition, cold-snare biopsies contained a higher number of T-cells (median: 71 × 10³ vs. 17 × 10³, p.05, Wilcoxon signed-rank test) and, most importantly, ILCs (median: 576 vs. 127, p.05, Wilcoxon signed-rank test, figure 1C and D). No intra-procedural AEs were observed. AEs were present in 17% of the patients, no serious AEs were reported (table 1). Conclusion Cold-snare specimen collection in IBD is technically feasible and yields higher numbers of viable immune cells, including rare immune cell subsets such as ILCs, compared with standard forceps biopsies. These findings support their potential as a valuable tissue source for advanced translational research. References: 1.Bernink JH, Peters CP, Munneke M, et al. Human type 1 innate lymphoid cells accumulate in inflamed mucosal tissues Nat Immunol. 2013;14(3):221-229. doi:10.1038/ni.2534 2.Elmunzer BJ, Higgins PD, Kwon YM, et al. Jumbo forceps are superior to standard large-capacity forceps in obtaining diagnostically adequate inflammatory bowel disease surveillance biopsy specimens. Gastrointest Endosc. 2008;68(2):273-336. doi:10.1016/j.gie.2007.11.023. 3.Busch CBE, van den Hoek K, Neefjes-Borst EA, Nieuwdorp M, van Baar ACG, Bergman JJHGM. Optimizing duodenal tissue acquisition for mechanistic studies of duodenal ablation in type 2 diabetes. Endosc Int Open. 2025;13:a25032135. Published 2025 Jan 29. doi:10.1055/a-2503-2135. Conflict of interest: Ms. Van Zon, Sarah: No conflict of interest Oldenburg, Lotte: No conflict of interest Nachataya, Katie: No conflict of interest Neefjes-Borst, Andra: No conflict of interest Goetgebuer, Rogier: Speaker fee Janssen-Cilag speaker fee Pfizer speaker fee Takeda Speaker fee Celltrion De Boer, Nanne: No conflict of interest Grootjans, Joep: No conflict of interest Bernink, Jochem: No conflict of interest D’Haens, Geert: Grant: Pfizer, BMS, Johnson and Johnson, Abbvie, Alimentiv BV, Eli Lilly, Takeda, Prometheus Laboratories Personal Fees: Abbvie, Abivax, Agomab, Alimentiv, Anaptys Bio, AstraZeneca, Bristol Meiers Squibb, Boehringer Ingelheim, Celltrion, Eli Lilly, Exeliom Biosciences, Galapagos, Glaxo Smith Kline, Dr Falk Pharma, Pfizer, Johnson and Johnson, Merck, Mirador, Polpharma, Procise Diagnostics, Prometheus Biosciences, Sorriso Pharma, Spyre, Takeda, Ventyx
Zon et al. (Thu,) studied this question.