title: Seroreactivity to microbial components in Crohn's disease is associated with ileal involvement, noninflammatory disease behavior and NOD2/CARD15 genotype, but not with risk for surgery in a Hungarian cohort of IBD patients.
abstract: BACKGROUND
  Antibodies directed against Saccharomyces cerevisiae (ASCA), perinuclear components of neutrophils (pANCA), and porin protein C of Escherichia coli (anti-OmpC) are reported to be associated with disease phenotype and may be of diagnostic importance in inflammatory bowel disease (IBD). Since limited data are available from Eastern Europe, we assessed the above antibodies in Hungarian IBD patients.
  
  
  METHODS
  In all, 653 well-characterized, unrelated consecutive IBD patients (Crohn's disease [CD]: 558, m/f: 263/295, duration: 8.1 +/- 10.7 years; ulcerative colitis [UC]: 95, m/f: 44/51, duration: 8.9 +/- 9.8 years) and 100 healthy subjects were investigated. Sera were assayed for anti-Omp and ASCA by enzyme-linked immunosorbent assay (ELISA) and ANCA by indirect immunofluorescence assay (IIF). TLR4 and NOD2/CARD15 variants were tested by polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP). Detailed clinical phenotypes were determined by reviewing the medical charts.
  
  
  RESULTS
  Anti-Omp, ASCA, and atypical pANCA antibodies were present in 31.2%, 59.3%, and 13.8% of CD, 24.2%, 13.7%, and 48.5% of UC patients, and in 20%, 16%, and 5.6% of controls, respectively. ASCA and anti-Omp positivity were associated with increased risk for CD (odds ratio [OR](ASCA) = 7.65, 95% confidence interval [CI]: 4.37-13.4; OR(Omp) = 1.81, 95% CI: 1.08-3.05). In a logistic regression analysis, anti-Omp and ASCA were independently associated with ileal and noninflammatory disease, but not with a risk for surgery or response to steroids or infliximab. A serology dosage effect was also observed. ASCA and anti-Omp antibodies were associated with NOD2/CARD15, in addition to a gene dosage effect. No associations were found in UC.
  
  
  CONCLUSIONS
  Serological markers were useful in the differentiation between CD and UC in an Eastern European IBD cohort. Reactivity to microbial components was associated with disease phenotype and NOD2/CARD15 genotype, further supporting the role of altered microbial sensing in the pathogenesis of CD.
authors.affiliation: 2nd Department of Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: Maria
authors.initials: M
authors.lastname: Papp
authors.forename: Istvan
authors.initials: I
authors.lastname: Altorjay
authors.forename: Gary L
authors.initials: GL
authors.lastname: Norman
authors.forename: Zakera
authors.initials: Z
authors.lastname: Shums
authors.forename: Karoly
authors.initials: K
authors.lastname: Palatka
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Vitalis
authors.forename: Ildiko
authors.initials: I
authors.lastname: Foldi
authors.forename: Gabriella
authors.initials: G
authors.lastname: Lakos
authors.forename: Judit
authors.initials: J
authors.lastname: Tumpek
authors.forename: Miklos L
authors.initials: ML
authors.lastname: Udvardy
authors.forename: Jolan
authors.initials: J
authors.lastname: Harsfalvi
authors.forename: Simon
authors.initials: S
authors.lastname: Fischer
authors.forename: Laszlo
authors.initials: L
authors.lastname: Lakatos
authors.forename: Agota
authors.initials: A
authors.lastname: Kovacs
authors.forename: Laszlo
authors.initials: L
authors.lastname: Bene
authors.forename: Tamas
authors.initials: T
authors.lastname: Molnar
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Tulassay
authors.forename: Pal
authors.initials: P
authors.lastname: Miheller
authors.forename: Gabor
authors.initials: G
authors.lastname: Veres
authors.forename: Janos
authors.initials: J
authors.lastname: Papp
authors.forename: Peter Laszlo
authors.initials: PL
authors.lastname: Lakatos
mesh_terms: D000328:Adult; D000906:Antibodies / Q000097:blood*; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology; D003093:Colitis, Ulcerative / Q000235:genetics / Q000276:immunology* / Q000601:surgery; D003424:Crohn Disease / Q000235:genetics / Q000276:immunology* / Q000601:surgery; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli / Q000276:immunology; D005260:Female; D015200:Fluoroimmunoassay; D005838:Genotype; D006801:Humans; D006814:Hungary; D008297:Male; D009154:Mutation; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D018272:Porins / Q000276:immunology; D012441:Saccharomyces cerevisiae / Q000276:immunology
chemical_list: D000906:Antibodies; D019268:Antibodies, Antineutrophil Cytoplasmic; D053473:Nod2 Signaling Adaptor Protein; D018272:Porins