New serological markers for inflammatory bowel disease are associated with earlier age at onset, complicated disease behavior, risk for surgery, and NOD2/CARD15 genotype in a Hungarian IBD cohort.
BACKGROUND
Antibodies to Saccharomyces cerevisiae (S. cerevisiae) (ASCA) and porin protein-C of Escherichia coli (anti-OmpC) are associated with disease phenotype and may be of diagnostic importance in inflammatory bowel diseases (IBD). Our aim was to determine whether a panel of new antibodies against bacterial proteins and carbohydrates could help differentiate among the various forms of IBD, and whether they were associated with particular clinical manifestations in a Hungarian cohort of IBD patients.


METHODS
Six hundred fifty-two well-characterized, unrelated, consecutive IBD patients (CD [Crohn's disease] 557, men/women 262/295, duration 8.1 +/- 11.3 yr; ulcerative colitis [UC] 95, men/women 44/51, duration 8.9 +/- 9.8 yr) and 100 healthy and 48 non-IBD gastrointestinal (GI) controls were investigated. Sera were assayed for anti-OmpC and antibodies against a mannan epitope of S. cerevisiae (gASCA), laminaribioside (ALCA), chitobioside (ACCA), and mannobioside (AMCA). 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 patients' medical charts.


RESULTS
Sixty-six percent of the CD patients had at least one of the investigated antibodies. Among glycan antibodies, gASCA or the combination of gASCA and atypical perinuclear antineutrophil cytoplasmic antibodies (pANCA) was most accurate for differentiating between CD and UC. ASCA and gASCA assays performed similarly. Increasing amount and level of antibody responses toward gASCA, ALCA, ACCA, AMCA, and OmpC were associated with more complicated disease behavior (P < 0.0001) and need for surgery in CD (P= 0.023). A serological dosage effect was also observed. gASCA and AMCA antibodies were associated with NOD2/CARD15, in addition to a gene-dosage effect. No serotype-phenotype associations were found in UC.


CONCLUSIONS
Antibody response to this new panel of serological markers was associated with complicated disease phenotype, NOD2/CARD15 genotype, and a need for surgery in this eastern European IBD cohort.
2nd Department of Medicine, University of Debrecen, Debrecen, Hungary.
Maria
M
Papp
Istvan
I
Altorjay
Nir
N
Dotan
Karoly
K
Palatka
Ildiko
I
Foldi
Judit
J
Tumpek
Sandor
S
Sipka
Miklos
M
Udvardy
Tamas
T
Dinya
Laszlo
L
Lakatos
Agota
A
Kovacs
Tamas
T
Molnar
Zsolt
Z
Tulassay
Pal
P
Miheller
Gary L
GL
Norman
Tamas
T
Szamosi
Janos
J
Papp
Peter L
PL
Lakatos
D000328:Adult; D017668:Age of Onset; D000906:Antibodies / Q000097:blood*; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D002686:Chitin / Q000276:immunology; D003093:Colitis, Ulcerative / Q000235:genetics / Q000276:immunology / Q000473:pathology* / Q000601:surgery; D003424:Crohn Disease / Q000235:genetics / Q000276:immunology / Q000473:pathology* / Q000601:surgery; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D006814:Hungary; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D009154:Mutation; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic; D011134:Polysaccharides / Q000276:immunology*; D012441:Saccharomyces cerevisiae / Q000276:immunology; D012680:Sensitivity and Specificity
D000906:Antibodies; D001425:Bacterial Outer Membrane Proteins; D015415:Biomarkers; D005819:Genetic Markers; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D053473:Nod2 Signaling Adaptor Protein; D011134:Polysaccharides; D002686:Chitin