title: Predicting complicated Crohn's disease and surgery: phenotypes, genetics, serology and psychological characteristics of a population-based cohort.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: J D
authors.initials: JD
authors.lastname: Ryan
authors.forename: M S
authors.initials: MS
authors.lastname: Silverberg
authors.forename: W
authors.initials: W
authors.lastname: Xu
authors.forename: L A
authors.initials: LA
authors.lastname: Graff
authors.forename: L E
authors.initials: LE
authors.lastname: Targownik
authors.forename: J R
authors.initials: JR
authors.lastname: Walker
authors.forename: R
authors.initials: R
authors.lastname: Carr
authors.forename: I
authors.initials: I
authors.lastname: Clara
authors.forename: N
authors.initials: N
authors.lastname: Miller
authors.forename: L
authors.initials: L
authors.lastname: Rogala
authors.forename: C N
authors.initials: CN
authors.lastname: Bernstein
mesh_terms: D000222:Adaptation, Physiological; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood*; D000071183:Autophagy-Related Proteins; D015415:Biomarkers / Q000097:blood; D002352:Carrier Proteins / Q000235:genetics*; D015331:Cohort Studies; D003424:Crohn Disease / Q000175:diagnosis* / Q000235:genetics / Q000523:psychology / Q000601:surgery; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D010641:Phenotype; D011237:Predictive Value of Tests; D018123:Receptors, Interleukin / Q000235:genetics*; D012307:Risk Factors; D012441:Saccharomyces cerevisiae / Q000276:immunology*
chemical_list: C518959:ATG16L1 protein, human; D000907:Antibodies, Bacterial; D000071183:Autophagy-Related Proteins; D015415:Biomarkers; D002352:Carrier Proteins; C515500:IL23R protein, human; D053473:Nod2 Signaling Adaptor Protein; D018123:Receptors, Interleukin