Antibodies to CBir1 flagellin define a unique response that is associated independently with complicated Crohn's disease.
OBJECTIVE
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.
Targan
Stephan R
SR
Cedars-Sinai Inflammatory Bowel Disease Center, Los Angeles, California 90048, USA. targans@cshs.org
Landers
Carol J
CJ
Yang
Huiying
H
Lodes
Michael J
MJ
Cong
Yingzi
Y
Papadakis
Konstantinos A
KA
Vasiliauskas
Eric
E
Elson
Charles O
CO
Hershberg
Robert M
RM
D000818:Animals; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology; D000907:Antibodies, Bacterial; D000917:Antibody Formation; D000942:Antigens, Bacterial; D016022:Case-Control Studies; D003424:Crohn Disease / Q000150:complications / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005408:Flagellin / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis*; D051379:Mice; D008809:Mice, Inbred C3H
D019268:Antibodies, Antineutrophil Cytoplasmic; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; C502160:CBir1 flagellin; D007074:Immunoglobulin G; D005408:Flagellin