Gastroenterology

Gastroenterology

Volume 126, Issue 2, February 2004, Pages 414-424
Gastroenterology

Clinical-alimentary tract
Association of antibody responses to microbial antigens and complications of small bowel Crohn’s disease

https://doi.org/10.1053/j.gastro.2003.11.015Get rights and content

Abstract

Background & Aims: Crohn’s disease patients can be characterized by antibody responses against Crohn’s disease-related bacterial sequence, Escherichia coli outer membrane porin C, Saccharomyces cerevisiae (oligomannan), and neutrophil nuclear antigens. Our aim was to determine whether expression of antibodies against Crohn’s disease-related bacterial sequence and Escherichia coli outer membrane porin C is associated with distinct phenotypic manifestations. Methods: Sera from 303 patients were tested for antibodies to the Crohn’s disease-related bacterial sequence (I2), anti-Escherichia coli outer membrane porin C, anti-Saccharomyces cerevisiae, and perinuclear antineutrophil cytoplasmic antibodies and for 3 Crohn’s disease-associated variants of the NOD2 gene (R702W, G908R, and 1007fs) and compared with clinical data. Results: Patients expressing I2 were more likely to have fibrostenosing Crohn’s disease (64.4% vs. 40.7%; P < 0.001) and to require small bowel surgery (62.2% vs. 37.4%; P < 0.001). Patients with anti-Escherichia coli outer membrane porin C were more likely to have internal perforating disease (50.0% vs. 30.7%; P = 0.001) and to require small bowel surgery (61.4% vs. 44.2%; P = 0.003). Anti-Crohn’s disease-related bacterial sequence was independently associated with fibrostenosis (P = 0.027) and small bowel surgery (P = 0.01), whereas anti-Escherichia coli outer membrane porin C was independently associated with internal perforations (P < 0.006). Patients positive for I2, anti-Escherichia coli outer membrane porin C, and anti-Saccharomyces cerevisiae were the most likely to have undergone small bowel surgery (72.0%; odds ratio, 8.6; P < 0.001) compared with patients without reactivity (23.0%). When the presence and magnitude of antibody responses were considered, 90% of patients with small bowel disease who required surgery had high levels of I2, Escherichia coli outer membrane porin C, and oligomannan antibodies, compared with only 18.2% with low-titer responses (P < 0.001). Conclusions: I2 and anti-Escherichia coli outer membrane porin C are associated with Crohn’s disease phenotypes, and patients with the highest level of serum reactivity toward an increasing number of microbiota have the greatest frequency of strictures, internal perforations, and small bowel surgery.

Section snippets

Patients

The cohort of 303 patients was ascertained from patients assessed at the Cedars-Sinai Medical Center from 1993 to 2002. All research-related activities were approved by the Cedars-Sinai Medical Center Institutional Review Board. The diagnosis of CD was based on standard endoscopic, histological, and radiographic features. At least 2 of the following characteristics were required for diagnosis: (1) clinical—perforating or fistulizing disease and obstructive symptoms secondary to stenosis or

Clinical, serological, and genetic characteristics of the study population

The relationship of individual antibody responses toward microbial antigens and autoantigens and disease phenotype has been reported previously. These prior studies indicate that in CD, a proportion of patients have serum reactivity against oligomannans (ASCA; 40%–60%),18, 35, 36 toward I2 (54%),17 and toward OmpC (56%)17 and exhibit pANCA (10%–40%).19 The first task was to determine the serum reactivity to each of these antigens in our cohort of CD patients. Figure 1 shows the scatter graph

Discussion

The pathogenesis of CD involves the aberrant recognition of luminal microbial antigens. In this study, we examined the relationship between humoral responses to microbial antigens and clinical manifestations in CD. Patients with CD can be grouped by their antibody responses toward individual microbial antigens and autoantigens, as evidenced by antibody responses toward I2 and OmpC and the expression of ASCA and pANCA.17 We hypothesized that in genetically predisposed hosts, these antibody

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  • Cited by (0)

    Supported by National Institutes of Health/Public Health Service grants PO1-DK46763 and RO1-DK54967, National Institutes of Health GI Training grant T32 DK07180-27, the Cedars-Sinai Board of Governors Chair in Medical Genetics, the Feintech Family Chair in Inflammatory Bowel Disease, and the Eli and Edythe Broad Medical Research Foundation.

    1

    Drs. Targan and Landers have an equity interest in Prometheus Laboratories. Dr. Abreu-Martin is a consultant for Prometheus Laboratories.

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