Serum C-X-C motif chemokine ligand 9, interleukin 8, and interleukin 22 as key biomarkers in pediatric inflammatory bowel disease

doi:10.3748/wjg.v31.i46.113172

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Gastroenterol. Dec 14, 2025; 31(46): 113172
Published online Dec 14, 2025. doi: 10.3748/wjg.v31.i46.113172

Serum C-X-C motif chemokine ligand 9, interleukin 8, and interleukin 22 as key biomarkers in pediatric inflammatory bowel disease

Adi Eindor-Abarbanel, Kevin Tsai, Ash Sandhu, Bruce Vallance, Kevan Jacobson

Adi Eindor-Abarbanel, Department of Pediatric Gastroenterology, Shamir Medical Center Affiliated to Grey's Medical School Tel Aviv University, Zrifin 70300, Israel

Kevin Tsai, Bruce Vallance, The Gut4Health Microbiome Core, Research Institute, British Columbia Children’s Hospital, Vancouver V6H 3V4, British Columbia, Canada

Ash Sandhu, Division of Biostatistics, Research Institute, British Columbia Children's Hospital, Vancouver V6H 3V4, British Columbia, Canada

Kevan Jacobson, Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Faculty of Medicine, British Columbia Children’s Hospital, University of British Columbia, Vancouver V6H 3V4, British Columbia, Canada

Author contributions: Eindor-Abarbanel A collected the data, conceived the study, wrote the manuscript, and performed part of the analysis; Tsai K was responsible for the study design and performed the analysis; Sandhu A was responsible for the statistical analysis and wrote parts of the manuscript; Vallance B was responsible for supervising the study and reviewed the manuscript; Jacobson K was responsible for the study design, supervision, and patient recruitment.

Supported by the Lutsky Family Foundation and AdMare Bioinnovations (previously known as the Genome BC CDRD Development Fund).

Institutional review board statement: The study was approved by the British Columbia Children's Hospital Ethics Committee (Approval No. H10-01760).

Informed consent statement: All parents or legal guardians of participants provided written informed consent.

Conflict-of-interest statement: Jacobson K is advisor/speaker of AbbVie Canada; advisor/consultant of AbbVie Canada, McKesson Canada, Janssen Canada, Viatris Canada, Celltrion Canada, CSL Behring Inc Canada; and stock options of Engene Inc Canada. All other authors declare no conflict of interest.

STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.

Data sharing statement: Data will be shared upon request from the corresponding author.

Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/

Corresponding author: Kevan Jacobson, MD, Professor, Senior Scientist, Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Faculty of Medicine, British Columbia Children’s Hospital, University of British Columbia, 4480 Oak Street, Room K4-184, Vancouver V6H 3V4, British Columbia, Canada. kjacobson@cw.bc.ca

Received: August 18, 2025
Revised: September 9, 2025
Accepted: October 27, 2025
Published online: December 14, 2025
Processing time: 115 Days and 1.5 Hours

Abstract

BACKGROUND

The diagnosis of inflammatory bowel disease (IBD) involves clinical, endoscopic, and radiologic evaluation. Endoscopic procedures, particularly in pediatrics, require general anesthesia and carry potential risks.

AIM

To investigate whether serum biomarkers can differentiate between pediatric patients with and without IBD. Secondary objectives included identifying biomarkers that distinguish Crohn’s disease (CD) from ulcerative colitis (UC) and assessing their predictive value for progression to biologic therapy.

METHODS

Pediatric patients undergoing diagnostic colonoscopy at British Columbia Children’s Hospital between December 2017 and June 2022 were enrolled. Blood samples were collected at colonoscopy, and demographic clinical data, laboratory, and histopathologic evaluation were obtained. An exploratory screen of 50 biomarkers was undertaken in a subset of patients (54 IBD, 41 controls) using Legendplex^TM flow cytometry kits to identify candidates. A refined panel of 12 serum biomarkers was subsequently selected and a supervised learning model was developed to classify patients.

RESULTS

The study included 246 pediatric patients, who had a median age of 13.03 years and were 37.4% female (103 CD, 52 UC, 91 controls). In univariate analyses, C-X-C motif chemokine ligand 9 (CXCL9) was the only biomarker significantly elevated in IBD vs controls (P < 0.001). A multivariable model achieved an area under the receiver operating characteristic of 0.861 for distinguishing IBD from controls. Interleukin 8 (IL-8) emerged as a key biomarker alongside CXCL9 and IL-22 in the model. The random forest model identified CXCL9 with the greatest diagnostic accuracy (area under the curve [AUC] = 0.81), followed by IL8 and IL22 (AUC = 0.737 and 0.68, respectively). CXCL9 and IL-18 showed higher levels in CD (P = 0.016), whereas CXCL1 levels predicted progression to biologic therapy within 1 year (P = 0.039). However, the model did not effectively predict disease subclassification or progression to biologic therapy.

CONCLUSION

Serum biomarkers, particularly CXCL9, IL-8, and IL-22, can aid in the diagnosis of pediatric IBD. CXCL9 and IL18 were found to be significant predictors of CD, and CXCL1 differed between patients requiring biologic therapy vs those who did not.

Keywords: C-X-C motif chemokine ligand 9; Interleukin 18; Interleukin 22; C-X-C motif chemokine ligand 1; Pediatric inflammatory bowel disease

Core Tip: The diagnosis of pediatric inflammatory bowel disease (IBD) usually requires invasive endoscopy under anesthesia, which carries risks in children. In this study, we evaluated serum cytokines as potential non-invasive biomarkers to distinguish pediatric IBD from non-IBD controls. Among over 250 pediatric patients, C-X-C motif chemokine ligand 9 (CXCL9), interleukin 8 (IL-8), and IL-22 emerged as key markers with strong discriminatory capacity. CXCL9 and IL-18 differentiated Crohn’s disease from ulcerative colitis, whereas CXCL1 levels were associated with the need for biologic therapy within 1 year. These findings suggest that specific serum biomarkers may support earlier diagnosis and aid in patient stratification.