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

Papp, Mária and Altorjay, István and Dotan, Nir and Palatka, Károly and Földi, Ildikó and Tumpek, Judit and Sipka, Sándor and Udvardy, Miklós and Dinya, Tamás and Lakatos, László and Kovács, Ágota and Molnár, Tamás and Tulassay, Zsolt and Miheller, Pál and Norman, Gary L. and Szamosi, Tamás and Papp, János and Lakatos, Péter László (2008) 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. American Journal of Gastroenterology, 103 (3). pp. 665-681. ISSN 0002-9270 (print), 1572-0241 (online)

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Abstract

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.

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