Antibodies to CBir1 flagellin define a unique response that is associated independently with complicated Crohn's disease

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

Research output: Contribution to journalArticle

345 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2020-2028
Number of pages9
JournalGastroenterology
Volume128
Issue number7
DOIs
StatePublished - Jun 2005
Externally publishedYes

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Crohn Disease
Antibodies
Antibody Formation
Phenotype
Antigens
Saccharomyces cerevisiae
Serum
Bacterial Antigens
Inbred C3H Mouse
Colitis
CBir1 flagellin
Ulcerative Colitis
Anti-Idiotypic Antibodies
Neutrophils
Immunoglobulin G
Enzyme-Linked Immunosorbent Assay

ASJC Scopus subject areas

  • Gastroenterology

Cite this

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.

In: Gastroenterology, Vol. 128, No. 7, 06.2005, p. 2020-2028.

Research output: Contribution to journalArticle

Targan, SR, Landers, CJ, Yang, H, Lodes, MJ, Cong, Y, Papadakis, KA, Vasiliauskas, E, Elson, CO & Hershberg, RM 2005, 'Antibodies to CBir1 flagellin define a unique response that is associated independently with complicated Crohn's disease', Gastroenterology, vol. 128, no. 7, pp. 2020-2028. https://doi.org/10.1053/j.gastro.2005.03.046
Targan, Stephan R. ; Landers, Carol J. ; Yang, Huiying ; Lodes, Michael J. ; Cong, Yingzi ; Papadakis, Konstantinos A. ; Vasiliauskas, Eric ; Elson, Charles O. ; Hershberg, Robert M. / Antibodies to CBir1 flagellin define a unique response that is associated independently with complicated Crohn's disease. In: Gastroenterology. 2005 ; Vol. 128, No. 7. pp. 2020-2028.
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abstract = "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.",
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T1 - Antibodies to CBir1 flagellin define a unique response that is associated independently with complicated Crohn's disease

AU - Targan, Stephan R.

AU - Landers, Carol J.

AU - Yang, Huiying

AU - Lodes, Michael J.

AU - Cong, Yingzi

AU - Papadakis, Konstantinos A.

AU - Vasiliauskas, Eric

AU - Elson, Charles O.

AU - Hershberg, Robert M.

PY - 2005/6

Y1 - 2005/6

N2 - 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.

AB - 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.

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