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Immune response and barrier dysfunction-related proteomic signatures in preclinical phase of Crohn's disease highlight earliest events of pathogenesis

Leibovitzh, Haim (författare)
Zane Cohen Centre for Digestive Diseases, Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada; Division of Gastroenterology & Hepatology, University of Toronto Temerty Faculty of Medicine, Toronto, Ontario, Canada
Lee, Sun Ho (författare)
Zane Cohen Centre for Digestive Diseases, Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada; Division of Gastroenterology & Hepatology, University of Toronto Temerty Faculty of Medicine, Toronto, Ontario, Canada
Raygoza Garay, Juan Antonio (författare)
Zane Cohen Centre for Digestive Diseases, Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada; Division of Gastroenterology & Hepatology, University of Toronto Temerty Faculty of Medicine, Toronto, Ontario, Canada
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Espin-Garcia, Osvaldo (författare)
Division of Biostatistics, University of Toronto Dalla Lana School of Public Health, Toronto, Ontario, Canada
Xue, Mingyue (författare)
Zane Cohen Centre for Digestive Diseases, Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
Neustaeter, Anna (författare)
Zane Cohen Centre for Digestive Diseases, Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
Goethel, Ashleigh (författare)
Zane Cohen Centre for Digestive Diseases, Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
Huynh, Hien Q. (författare)
Division of Gastroenterology and Nutrition, Department of Pediatrics, University of Alberta Faculty of Medicine & Dentistry, Edmonton, Alberta, Canada
Griffiths, Anne M. (författare)
IBD Center, Department of Paediatrics, Faculty of Medicine, University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada
Turner, Dan (författare)
The Juliet Keidan Institute of Pediatric Gastroenterology and Nutrition, The Hebrew University of Jerusalem, Shaare Zedek Medical Center, Jerusalem, Israel
Madsen, Karen L. (författare)
Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
Moayyedi, Paul (författare)
Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
Steinhart, A. Hillary (författare)
Zane Cohen Centre for Digestive Diseases, Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada; Division of Gastroenterology & Hepatology, University of Toronto Temerty Faculty of Medicine, Toronto, Ontario, Canada
Silverberg, Mark S. (författare)
Zane Cohen Centre for Digestive Diseases, Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada; Division of Gastroenterology & Hepatology, University of Toronto Temerty Faculty of Medicine, Toronto, Ontario, Canada
Deslandres, Colette (författare)
Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, University of Montreal, Saint Justine Hospital, Montreal, Quebec, Canada
Bitton, Alain (författare)
Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Quebec, Canada
Mack, David R. (författare)
Division of Gastroenterology, Hepatology & Nutrition, University of Ottawa, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada
Jacobson, Kevan (författare)
Canadian Gastro-Intestinal Epidemiology Consortium, British Columbia Children's Hospital Research Institute, University of British Columbia, British Columbia Children's Hospital, Vancouver, British Columbia, Canada
Cino, Maria (författare)
Department of Medicine, Division of Gastroenterology, University of Toronto, Toronto, Ontario, Canada
Aumais, Guy (författare)
Department of Medicine, Montreal University, Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada
Bernstein, Charles N. (författare)
University of Manitoba Inflammatory Bowel Disease Clinical and Research Centre and Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
Panaccione, Remo (författare)
Inflammatory Bowel Disease Clinic, Division of Gastroenterology and Hepatology of Gastroenterology, University of Calgary, Calgary, Alberta, Canada
Weiss, Batia (författare)
Division of Pediatric Gastroenterology, Hepatology and Nutrition, Sheba Medical Center, Tel-Hashomer, Sackler Faculty of Medicine, Tel-Aviv University, The Edmond and Lily Safra Children's Hospital, Tel Aviv, Israel
Halfvarson, Jonas, 1970- (författare)
Örebro universitet,Institutionen för medicinska vetenskaper,Department of Gastroenterology, Örebro University, Örebro, Sweden
Xu, Wei (författare)
Division of Biostatistics, University of Toronto Dalla Lana School of Public Health, Toronto, Ontario, Canada
Turpin, Williams (författare)
Zane Cohen Centre for Digestive Diseases, Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada; Division of Gastroenterology & Hepatology, University of Toronto Temerty Faculty of Medicine, Toronto, Ontario, Canada
Croitoru, Kenneth (författare)
Zane Cohen Centre for Digestive Diseases, Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada; Division of Gastroenterology & Hepatology, University of Toronto Temerty Faculty of Medicine, Toronto, Ontario, Canada
Crohn’s and Colitis Canada (CCC) Genetic, Environmental, Microbial (GEM) Project Research Consortium, - (bidragsgivare)
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 (creator_code:org_t)
2023-02-14
2023
Engelska.
Ingår i: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 72:8, s. 1462-1471
Relaterad länk:
https://urn.kb.se/re...
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https://doi.org/10.1...
http://kipublication...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • OBJECTIVE: The measure of serum proteome in the preclinical state of Crohn's disease (CD) may provide insight into biological pathways involved in CD pathogenesis. We aimed to assess associations of serum proteins with future CD onset and with other biomarkers predicting CD risk in a healthy at-risk cohort.DESIGN: In a nested case-control study within the Crohn's and Colitis Canada Genetics Environment Microbial Project (CCC-GEM) cohort, which prospectively follows healthy first-degree relatives (FDRs), subjects who developed CD (n=71) were matched with four FDRs remaining healthy (n=284). Using samples at recruitment, serum protein profiles using the Olink Proximity Extension Assay platform was assessed for association with future development of CD and with other baseline biomarkers as follows: serum antimicrobial antibodies (AS: positive antibody sum) (Prometheus); faecal calprotectin (FCP); gut barrier function using the fractional excretion of lactulose-to-mannitol ratio (LMR) assay.RESULTS: We identified 25 of 446 serum proteins significantly associated with future development of CD. C-X-C motif chemokine 9 (CXCL9) had the highest OR with future risk of CD (OR=2.07 per SD, 95% CI 1.58 to 2.73, q=7.9e-5), whereas matrix extracellular phosphoglycoprotein had the lowest OR (OR 0.44, 95% CI 0.29 to 0.66, q=0.02). Notably, CXCL9 was the only analyte significantly associated with all other CD-risk biomarkers with consistent direction of effect (FCP: OR=2.21; LMR: OR=1.67; AS: OR=1.59) (q<0.05 for all).CONCLUSION: We identified serum proteomic signatures associated with future CD development, reflecting potential early biological processes of immune and barrier dysfunction.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Gastroenterologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Gastroenterology and Hepatology (hsv//eng)

Nyckelord

CHEMOKINES
CROHN'S DISEASE
GUT INFLAMMATION
IMMUNE RESPONSE
INTESTINAL BARRIER FUNCTION

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