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.
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.
Papp
Maria
M
2nd Department of Medicine, University of Debrecen, Debrecen, Hungary.
Altorjay
Istvan
I
Norman
Gary L
GL
Shums
Zakera
Z
Palatka
Karoly
K
Vitalis
Zsuzsanna
Z
Foldi
Ildiko
I
Lakos
Gabriella
G
Tumpek
Judit
J
Udvardy
Miklos L
ML
Harsfalvi
Jolan
J
Fischer
Simon
S
Lakatos
Laszlo
L
Kovacs
Agota
A
Bene
Laszlo
L
Molnar
Tamas
T
Tulassay
Zsolt
Z
Miheller
Pal
P
Veres
Gabor
G
Papp
Janos
J
Lakatos
Peter Laszlo
PL
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
D000906:Antibodies; D019268:Antibodies, Antineutrophil Cytoplasmic; D053473:Nod2 Signaling Adaptor Protein; D018272:Porins