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Original article
Proteomic analysis of ascending colon biopsies from a paediatric inflammatory bowel disease inception cohort identifies protein biomarkers that differentiate Crohn's disease from UC
  1. Amanda E Starr1,
  2. Shelley A Deeke1,
  3. Zhibin Ning1,
  4. Cheng-Kang Chiang1,
  5. Xu Zhang1,
  6. Walid Mottawea1,2,
  7. Ruth Singleton3,
  8. Eric I Benchimol3,4,5,
  9. Ming Wen1,
  10. David R Mack3,4,
  11. Alain Stintzi1,
  12. Daniel Figeys1,6
  1. 1Department of Biochemistry, Microbiology and Immunology, Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada
  2. 2Department of Microbiology and Immunology, Mansoura University, Mansoura, Egypt
  3. 3Children's Hospital of Eastern Ontario (CHEO) Inflammatory Bowel Disease Centre and CHEO Research Institute, University of Ottawa, Ottawa, Ontario, Canada
  4. 4Department of Pediatrics, University of Ottawa, Ottawa, Ontario, Canada
  5. 5School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, Ontario, Canada
  6. 6Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Ontario, Canada
  1. Correspondence to Dr Daniel Figeys, Department of Biochemistry, Microbiology and Immunology, Ottawa Institute of Systems Biology, University of Ottawa, Roger Guidon Hall, 451 Smyth Road, University of Ottawa, Ottawa, Ontario, Canada K1H 8M5; dfigeys{at}uottawa.ca

Abstract

Objective Accurate differentiation between Crohn's disease (CD) and UC is important to ensure early and appropriate therapeutic intervention. We sought to identify proteins that enable differentiation between CD and UC in children with new onset IBD.

Design Mucosal biopsies were obtained from children undergoing baseline diagnostic endoscopy prior to therapeutic interventions. Using a super-stable isotope labeling with amino acids in cell culture (SILAC)-based approach, the proteomes of 99 paediatric control and biopsies of patients with CD and UC were compared. Multivariate analysis of a subset of these (n=50) was applied to identify novel biomarkers, which were validated in a second subset (n=49).

Results In the discovery cohort, a panel of five proteins was sufficient to distinguish control from IBD-affected tissue biopsies with an AUC of 1.0 (95% CI 0.99 to 1.0); a second panel of 12 proteins segregated inflamed CD from UC within an AUC of 0.95 (95% CI 0.86 to 1.0). Application of the two panels to the validation cohort resulted in accurate classification of 95.9% (IBD from control) and 80% (CD from UC) of patients. 116 proteins were identified to have correlation with the severity of disease, four of which were components of the two panels, including visfatin and metallothionein-2.

Conclusions This study has identified two panels of candidate biomarkers for the diagnosis of IBD and the differentiation of IBD subtypes to guide appropriate therapeutic interventions in paediatric patients.

  • IBD
  • CROHN'S DISEASE
  • ULCERATIVE COLITIS
  • IBD BASIC RESEARCH

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/

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