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Serological markers predict inflammatory bowel disease years before the diagnosis
  1. Fiona D M van Schaik1,
  2. Bas Oldenburg1,
  3. Andrew R Hart2,
  4. Peter D Siersema1,
  5. Stefan Lindgren3,
  6. Olof Grip3,
  7. Birgit Teucher4,
  8. Rudolf Kaaks4,
  9. Manuela M Bergmann5,
  10. Heiner Boeing5,
  11. Franck Carbonnel6,
  12. Prevost Jantchou6,
  13. Marie-Christine Boutron-Ruault6,
  14. Anne Tjønneland7,
  15. Anja Olsen7,
  16. Francesca L Crowe8,
  17. Petra H M Peeters9,
  18. Martijn G H van Oijen1,
  19. H Bas Bueno-de-Mesquita1
  1. 1Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands
  2. 2Norwich Medical School, University of East Anglia, Norwich, UK
  3. 3Department of Clinical Sciences, Lund University, Malmö, Sweden
  4. 4Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany
  5. 5Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbrücke, Germany
  6. 6Center for Research in Epidemiology and Population Health, Inserm U1018 Team 9, Paris South University, Institut Gustave-Roussy, Villejuif, France
  7. 7Unit of Diet, Genes, and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark
  8. 8Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK
  9. 9Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
  1. Correspondence to Dr Bas Oldenburg, Department of Gastroenterology and Hepatology, University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands; b.oldenburg{at}


Objective Anti-neutrophil cytoplasmic antibodies and anti-Saccharomyces cerevisiae mannan antibodies (ASCAs) have been detected in the serum of patients with ulcerative colitis (UC) and Crohn's disease (CD) and their unaffected family members. The aim of this study was to establish the value of serological markers as predictors of UC and CD.

Design Individuals who developed CD or UC were identified from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. At recruitment, none of the participants had a diagnosis of CD or UC. For each incident case, two controls were randomly selected matched for centre, date of birth, sex, date of recruitment and time of follow-up. Serum of cases and controls obtained at recruitment were analysed for ASCA IgG, ASCA IgA, perinuclear anti-neutrophil cytoplasmic antibody (pANCA), antibodies against Escherichia coli outer membrane porin C (OmpC) and flagellin CBir1. Conditional logistic regression was used to determine risk of CD and UC. Receiver operating characteristic curves were constructed to test accuracy.

Results A total of 77 individuals were diagnosed with CD and 167 with UC after a mean follow-up of 4.5 (SD 3.2) and 4.4 (SD 3.1) years following blood collection, respectively. Combinations of pANCA, ASCA, anti-CBir1 and anti-OmpC were most accurate in predicting incident CD and UC (area under curve 0.679 and 0.657, respectively). The predictive value of the combination of markers increased when time to diagnosis of CD or UC decreased.

Conclusion A panel of serological markers is able to predict development of CD and UC in individuals from a low-risk population.

  • Crohn's disease
  • ulcerative colitis
  • serology
  • predictive accuracy
  • inflammatory bowel disease
  • Crohn's colitis
  • dysplasia
  • colonic neoplasms
  • IBD clinical
  • gallstones
  • diverticular disease
  • IBD
  • quality of life
  • Barrett's metaplasia
  • Barrett's carcinoma
  • Barrett's oesophagus
  • oesophageal cancer
  • nonalcoholic steatohepatitis
  • nerve
  • gut interactions
  • autoimmune liver disease
  • liver
  • primary biliary cirrhosis
  • epidemiology
  • nutrition
  • cancer epidemiology

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  • Funding The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by the Dutch Ministry of Health, Welfare and Sports, Dutch Prevention Funds, LK Research Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (the Netherlands); Ligue contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM; France); German Cancer Aid, Federal Ministry of Education and Research (Germany); Danish Cancer Society (Denmark); Cancer Research UK, Medical Research Council, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, the Wellcome Trust (UK); Swedish Cancer Society, Swedish Scientific Council and Regional Government of Skåne (Sweden).

  • Competing interests None.

  • Patient consent This study was carried out with the approval of the International Agency for Research and Cancer Institutional Review Board and of all participating local ethics committees. At recruitment, all participants gave written informed consent for future use of their data and material. Due to the large number of participants included into the EPIC study and the large number of studies being performed with this cohort, control over the informed consents is managed by the local ethics committees. We are therefore unable to submit the individual written informed consents.

  • Ethics approval This study was carried out with the approval of the International Agency for Research and Cancer Institutional Review Board and that of local ethics committees in each center.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement There are no supplementary or underlying data related to this paper available for data sharing.

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