Predicting complicated Crohn's disease and surgery: phenotypes, genetics, serology and psychological characteristics of a population-based cohort

Aliment Pharmacol Ther. 2013 Aug;38(3):274-83. doi: 10.1111/apt.12368. Epub 2013 Jun 3.

Abstract

Background: Predictors of complicated Crohn's disease (CD), defined as stricturing or penetrating behaviour, and surgery have largely been derived from referral centre populations.

Aim: To investigate whether serological markers, susceptibility genes or psychological characteristics are associated with complicated CD or surgery in a population-based cohort.

Methods: One hundred and eighty-two members of the Manitoba IBD Cohort with CD phenotyped using the Montreal classification underwent genetic and serological analysis at enrolment and after 5 years. One hundred and twenty-seven had paired sera at baseline and 5 years later and their data were used to predict outcomes at a median of 9.3 years. Serological analysis consisted of a seven antibody panel, and DNA was tested for CD-associated NOD2 variants (rs2066845,rs2076756,rs2066847), ATG16L1 (rs3828309, rs2241880) and IL23R (rs11465804). Psychological characteristics were assessed using semi-structured interviews and validated survey measures.

Results: Sixty-five per cent had complicated CD and 42% underwent surgery. Multivariate analysis indicated that only ASCA IgG-positive serology was predictive of stricturing/penetrating behaviour (OR = 3.01; 95% CI: 1.28-7.09; P = 0.01) and ileal CD (OR = 2.2; 95% CI: 1.07-4.54, P = 0.03). Complicated CD behaviour was strongly associated with surgery (OR = 5.6; 95% CI: 2.43-12.91; P < 0.0001), whereas in multivariate analysis, only ASCA IgG was associated (OR = 2.66; 95% CI, 1.40-5.06, P = 0.003). ASCA titre results were similar at baseline and follow-up. Psychological characteristics were not significantly associated with disease behaviour, serological profile or genotype.

Conclusions: ASCA IgG at baseline was significantly associated with stricturing/penetrating disease at 9-10 years from diagnosis. Stricturing/penetrating disease was significantly associated with surgery. In a model including serology, the genotypes assessed did not significantly associate with complicated disease or surgery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological
  • Adult
  • Antibodies, Bacterial / blood*
  • Autophagy-Related Proteins
  • Biomarkers / blood
  • Carrier Proteins / genetics*
  • Cohort Studies
  • Crohn Disease / diagnosis*
  • Crohn Disease / genetics
  • Crohn Disease / psychology
  • Crohn Disease / surgery
  • DNA Mutational Analysis
  • Female
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Male
  • Multivariate Analysis
  • Nod2 Signaling Adaptor Protein / genetics*
  • Phenotype
  • Predictive Value of Tests
  • Receptors, Interleukin / genetics*
  • Risk Factors
  • Saccharomyces cerevisiae / immunology*

Substances

  • ATG16L1 protein, human
  • Antibodies, Bacterial
  • Autophagy-Related Proteins
  • Biomarkers
  • Carrier Proteins
  • IL23R protein, human
  • Nod2 Signaling Adaptor Protein
  • Receptors, Interleukin