Serum Analyte Profiles Associated With Crohn’s Disease and Disease Location
Author:
Boucher Gabrielle1, Paradis Alexandre2, Chabot-Roy Geneviève2, Coderre Lise2, Hillhouse Erin E2, Bitton Alain3, Des Rosiers Christine14, Levings Megan K5, Schumm L Philip6, Lazarev Mark7, Brant Steve R78, Duerr Richard9, McGovern Dermot10, Silverberg Mark S11, Cho Judy12, Lesage Sylvie213, Rioux John D114ORCID, Bitton Alain, Boucher Gabrielle, Charron Guy, Des Rosiers Christine, Forest Anik, Goyette Philippe, Ivinson Sabine, Joseph Lawrence, Kohen Rita, Lachaine Jean, Lesage Sylvie, Levings Megan, Rioux John D, Thompson-Legault Julie, Vachon Luc, Veilleux Sophie, White-Guay Brian, Bajpai Manisha, Birch Sondra, Bitton Alain, Borowski Krzysztof, Botwin Gregory, Boucher Gabrielle, Brant Steven R, Chen Wei, Cho Judy H, Cordero Roberto, Côté-Daigneault Justin, Daly Mark J, Datta Lisa, Duerr Richard H, Filice Melissa, Fleshner Philip, Gettler Kyle, Giri Mamta, Goyette Philippe, Hao Ke, Haritunians Talin, Itan Yuval, Johnston Elyse, Konnikova Liza, Landers Carol, Lazarev Mark, Li Dalin, McGovern Dermot P B, Mengesha Emebet, Merad Miriam, Miladinova Vessela, Nayeri Shadi, Proksell Siobhan, Raquel Milgrom, Rioux John D, Rymaszewski Klaudia, Sabic Ksenija, Sands Bruce, Schumm L Philip, Schwartz Marc B, Silverberg Mark S, Simpson Claire L, Stempak Joanne M, Stevens Christine, Targan Stephan R, Xavier Ramnik, ,
Affiliation:
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
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.
Funder
National Institute of Diabetes and Digestive and Kidney Diseases Canada Research Chairs Canada Foundation for Innovation
Publisher
Oxford University Press (OUP)
Subject
Gastroenterology,Immunology and Allergy
Cited by
10 articles.
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