title: Sero-reactivity to microbial components in Crohn's disease is associated with disease severity and progression, but not NOD2/CARD15 genotype.
abstract: OBJECTIVE
  Antibodies directed against the porin protein C of Escherichia coli (anti-OmpC) and Pseudomonas fluorescens (anti-I2) have recently been described in Crohn's disease (CD). Those directed against Saccharomyces cerevisiae (ASCA) and the perinuclear component of neutrophils (pANCA) have been more widely studied and may be of diagnostic importance. We aimed to assess the frequency of anti-OmpC, anti-I2, ASCA, and pANCA, in an independent Scottish CD cohort, establish phenotypic associations, and compare with a U.S. cohort.
  
  
  METHODS
  One hundred and forty-two well-characterized CD patients (76 females, median age 39 yr (17-88)) were studied. CD was classified by the Vienna classification. Sera were assayed for anti-OmpC, anti-I2, ASCA, and pANCA. Allele specific primers were used for NOD2/CARD15 genotyping.
  
  
  RESULTS
  Anti-OmpC, anti-I2, ASCA, and pANCA were present in sera from 37%, 52%, 39%, and 14% of CD patients, respectively. Multivariate analysis demonstrated independent associations of anti-OmpC to be progression of disease type (p= 0.005) and long disease duration (p= 0.002), and those of anti-I2 to be long disease duration (p= 0.002) and the need for surgery (p= 0.033). ASCA were associated with disease progression (p < 0.001). When the presence and magnitude of all antibody responses were considered, reactivity to microbial components was associated with long disease duration (p < 0.001), progression of disease type (p < 0.001), penetrating disease (p= 0.008), small bowel disease (p < 0.02), and the need for surgery (p < 0.001). There was no association of antibody status to NOD2/CARD15 genotype.
  
  
  CONCLUSIONS
  Reactivity to microbial components is associated with severe CD characterized by small bowel involvement, frequent disease progression, longer disease duration, and greater need for intestinal surgery.
authors.affiliation: Gastrointestinal Unit, University of Edinburgh Department of Medical Sciences, School of Clinical and Molecular Medicine, Western General Hospital, Edinburgh EH4 2XU, UK.
authors.forename: Ian D R
authors.initials: ID
authors.lastname: Arnott
authors.forename: Carol J
authors.initials: CJ
authors.lastname: Landers
authors.forename: Elaine J
authors.initials: EJ
authors.lastname: Nimmo
authors.forename: Hazel E
authors.initials: HE
authors.lastname: Drummond
authors.forename: Ben K R
authors.initials: BK
authors.lastname: Smith
authors.forename: Stephan R
authors.initials: SR
authors.lastname: Targan
authors.forename: Jack
authors.initials: J
authors.lastname: Satsangi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000907:Antibodies, Bacterial / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology; D016009:Chi-Square Distribution; D003424:Crohn Disease / Q000235:genetics* / Q000276:immunology / Q000382:microbiology*; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D053473:Nod2 Signaling Adaptor Protein; D012441:Saccharomyces cerevisiae / Q000276:immunology*; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D047908:Intracellular Signaling Peptides and Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein