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

Targan, Stephan R.; Landers, Carol J.; Yang, Huiying; Lodes, Michael J.; Cong, Yingzi; Papadakis, Konstantinos A.; Vasiliauskas, Eric; Elson, Charles O.; Hershberg, Robert M.

doi:10.1053/j.gastro.2005.03.046

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

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

Stephan R. Targan
- Cedars-Sinai Inflammatory Bowel Disease Center, Los Angeles, California
- Address requests for reprints to: Stephan R. Targan, MD, Director, Division of Gastroenterology, Inflammatory Bowel Disease Center, and Immunobiology Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Suite D4063, Los Angeles, California 90048. fax: (310) 423-0224.
Carol J. Landers
- Cedars-Sinai Inflammatory Bowel Disease Center, Los Angeles, California
Huiying Yang
- Cedars-Sinai Inflammatory Bowel Disease Center, Los Angeles, California
Michael J. Lodes
- CombiMatrix Corporation, Seattle, Washington
- Cedars-Sinai Inflammatory Bowel Disease Center, Los Angeles, California
Yingzi Cong
- Division of Gastroenterology, University of Alabama, Birmingham, Alabama
- Cedars-Sinai Inflammatory Bowel Disease Center, Los Angeles, California
Konstantinos A. Papadakis
- Cedars-Sinai Inflammatory Bowel Disease Center, Los Angeles, California
Eric Vasiliauskas
- Cedars-Sinai Inflammatory Bowel Disease Center, Los Angeles, California
Charles O. Elson
- Division of Gastroenterology, University of Alabama, Birmingham, Alabama
- Cedars-Sinai Inflammatory Bowel Disease Center, Los Angeles, California
Robert M. Hershberg
- Dendreon Corporation, Seattle, Washington
- Cedars-Sinai Inflammatory Bowel Disease Center, Los Angeles, California

Received 29 June 2004; accepted 9 March 2005.

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.

Abbreviations used in this paper: ASCA, anti-Saccharomyces cerevisiae antibody , ANCA, antineutrophil cytoplasmic antibody , EU, enzyme-linked immunosorbant assay unit , pANCA, perinuclear antineutrophil cytoplasmic antibody , OmpC, Escherichia coli outer membrane porin C , I2, CD-related protein from Pseudomonas fluorescens (CD-related bacterial sequence).