Gastroenterology

Gastroenterology

Volume 128, Issue 7, June 2005, Pages 2020-2028
Gastroenterology

Basic-alimentary tract
Antibodies to CBir1 Flagellin Define a Unique Response That Is Associated Independently With Complicated Crohn’s Disease

https://doi.org/10.1053/j.gastro.2005.03.046Get rights and content

Background & Aims: Antibody responses to certain microbial antigens define heterogeneous groups of Crohn’s patients; multiple and high-level responses to these antigens are associated with aggressive clinical phenotypes. The flagellin, CBir1, identified by investigations in the C3H/HeJBir mouse model, has been identified as a dominant antigen capable of inducing colitis in mice and eliciting antibody responses in a subpopulation of patients with Crohn’s disease (CD). The aim of this study was to evaluate serum response to CBir1 flagellin in CD patients and to compare this response to responses defined previously to oligomannan (anti-Saccharomyces cerevisiae antibody), I2, OmpC, and neutrophil nuclear autoantigens (pANCA), and to determine anti-CBir1-associated phenotypes. Methods: A total of 484 sera from the Cedars Sinai Medical Center repository, previously typed for anti-Saccharomyces cerevisiae antibody, anti-I2, anti-OmpC, and pANCA were tested for anti-CBir1 by enzyme-linked immunosorbent assay, and results were assessed for clinical phenotype associations. Results: The presence and level of immunoglobulin G anti-CBir1 were associated with CD independently. Anti-CBir1 was present in all antibody subgroups and expression increased in parallel with increases in the number of antibody responses. pANCA+ CD patients were more reactive to CBir1 than were pANCA+ ulcerative colitis patients. Anti-CBir1 expression is associated independently with small-bowel, internal-penetrating, and fibrostenosing disease features. Conclusions: Serum responses to CBir1 independently identify a unique subset of patients with complicated CD. This bacterial antigen was identified in a murine model and has a similar pattern of aberrant reactivity in a subset of CD patients.

Section snippets

Patients

Serum samples from 484 patients (40 normal controls, 21 disease controls, 50 UC patients, and 373 CD patients) were selected from the serum archive of the Cedars-Sinai Inflammatory Bowel Disease Research Center. All research-related activities were approved by the Cedars-Sinai Medical Center institutional review board. The diagnosis for each patient was based on standard endoscopic, histologic, and radiographic features. The normal control group is a collection of environmental controls that

Serum Reactivity to CBir1 Defines a Subset of Patients With CD

Serologic expression cloning of a cecal bacterial antigen phage library identified the flagellin, CBir1, as an immunodominant antigen recognized by colitic mice21 and by approximately half of patients with CD. We used serum from 2 separate cohorts to investigate subgroups of CD patients. Cohort 1 consisted of sera from 100 CD patients selected on the basis of antibody profile. Newly tested sera from a group of 303 unselected patients that were studied and reported on by Mow et al20 comprised

Discussion

Our investigations have yielded compelling evidence that serum antibody to CBir1 flagellin marks for an independent subset of patients with CD. We have shown that the level of response can vary widely, that these responses are relatively stable over time, and these responses do not correspond with active or remission disease states. We know that anti-CBir1 expression is independent of serologic responses to previously defined bacterial antigens and is associated independently with complicated

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    Supported by United States Public Health Service grant PO1DK46763 and a grant from the Edythe and Eli Broad Foundation Medical Research Program.

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