Gabrielle Boucher1, Alexandre Paradis2, Geneviève Chabot-Roy2, Lise Coderre2, Erin E Hillhouse2, Alain Bitton3, Christine Des Rosiers1,4, Megan K Levings5, L Philip Schumm6, Mark Lazarev7, Steve R Brant7,8, Richard Duerr9, Dermot McGovern10, Mark S Silverberg11, Judy Cho12, Sylvie Lesage2,13, John D Rioux1,14. 1. Montreal Heart Institute, Montréal, Québec, Canada. 2. Maisonneuve-Rosemont Hospital Research Center, Montréal, Québec, Canada. 3. Division of Gastroenterology, McGill University, Montreal, Québec, Canada. 4. Département de Nutrition, Université de Montréal, Montréal, Québec, Canada. 5. BC Children's Hospital Research Institute, Vancouver, British Columbia, Canada. 6. Department of Public Health Sciences, University of Chicago, Chicago, Illinois, USA. 7. The Harvey M. and Lyn P. Meyerhoff Inflammatory Bowel Disease Center, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. 8. Division of Gastroenterology and Hepatology, Department of Medicine, Rutgers Robert Wood Johnson Medical School, and Department of Genetics and the Human Genetics Institute of New Jersey, Rutgers University, New Brunswick and Piscataway, New Jersey, USA. 9. Department of Medicine, University of Pittsburgh, Pennsylvania, USA. 10. F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA. 11. Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Mount Sinai Hospital Inflammatory Bowel Disease Centre, Toronto, Ontario, USA. 12. Icahn School of Medicine, Mount Sinai, New York, New York, USA. 13. Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, Québec, Canada. 14. Département de Médicine, Université de Montréal, Montréal, Québec, Canada.
Abstract
BACKGROUND: Crohn's disease (CD) can affect any segment of the digestive tract but is most often localized in the ileal, ileocolonic, and colorectal regions of the intestines. It is believed that the chronic inflammation in CD is a result of an imbalance between the epithelial barrier, the immune system, and the intestinal microbiota. The aim of the study was to identify circulating markers associated with CD and/or disease location in CD patients. METHODS: We tested 49 cytokines, chemokines, and growth factors in serum samples from 300 patients with CD and 300 controls. After quality control, analyte levels were tested for association with CD and disease location. RESULTS: We identified 13 analytes that were higher in CD patients relative to healthy controls and that remained significant after conservative Bonferroni correction (P < 0.0015). In particular, CXCL9, CXCL1, and interleukin IL-6 had the greatest effect and were highly significant (P < 5 × 10-7). We also identified 9 analytes that were associated with disease location, with VEGF, IL-12p70, and IL-6 being elevated in patients with colorectal disease (P < 3 × 10-4). CONCLUSIONS: Multiple serum analytes are elevated in CD. These implicate the involvement of multiple cell types from the immune, epithelial, and endothelial systems, suggesting that circulating analytes reflect the inflammatory processes that are ongoing within the gut. Moreover, the identification of distinct profiles according to disease location supports the existence of a biological difference between ileal and colonic CD, consistent with previous genetic and clinical observations.
BACKGROUND: Crohn's disease (CD) can affect any segment of the digestive tract but is most often localized in the ileal, ileocolonic, and colorectal regions of the intestines. It is believed that the chronic inflammation in CD is a result of an imbalance between the epithelial barrier, the immune system, and the intestinal microbiota. The aim of the study was to identify circulating markers associated with CD and/or disease location in CD patients. METHODS: We tested 49 cytokines, chemokines, and growth factors in serum samples from 300 patients with CD and 300 controls. After quality control, analyte levels were tested for association with CD and disease location. RESULTS: We identified 13 analytes that were higher in CD patients relative to healthy controls and that remained significant after conservative Bonferroni correction (P < 0.0015). In particular, CXCL9, CXCL1, and interleukin IL-6 had the greatest effect and were highly significant (P < 5 × 10-7). We also identified 9 analytes that were associated with disease location, with VEGF, IL-12p70, and IL-6 being elevated in patients with colorectal disease (P < 3 × 10-4). CONCLUSIONS: Multiple serum analytes are elevated in CD. These implicate the involvement of multiple cell types from the immune, epithelial, and endothelial systems, suggesting that circulating analytes reflect the inflammatory processes that are ongoing within the gut. Moreover, the identification of distinct profiles according to disease location supports the existence of a biological difference between ileal and colonic CD, consistent with previous genetic and clinical observations.
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