Anti-flagellin (CBir1) phenotypic and genetic Crohn's disease associations.
BACKGROUND
Antibody reactivity to microbial antigens correlates with distinct Crohn's disease (CD) phenotypes such as fistulizing or fibrostenosing disease. We examined the association between anti-CBir1 and clinical phenotypes and NOD2 variants in a large cohort of adult CD patients.


METHODS
Sera and genomic DNA were collected from 731 patients with CD and tested for immune responses to I2, CBir1, oligomannan, and outer membrane porin C (OmpC) and the 3 most common CD-associated NOD2 variants.


RESULTS
Anti-CBir1 reactivity was significantly associated with fibrostenosis (FS), internal penetrating (IP) disease phenotypes, small bowel (SB) involvement, and SB surgery but negatively associated with ulcerative colitis (UC)-like CD. Multivariate logistic regression analysis showed that anti-CBir1 was independently associated with FS and UC-like CD irrespective of the antibody reactivity to I2, oligomannan, or OmpC, but not with SB involvement or SB surgery. The magnitude of anti-CBir1 reactivity, when added to the quantitative response toward the other 3 CD-associated antigens, enhances the discrimination of FS, IP, UC-like CD, and SB involvement, but not SB surgery. Finally, although the frequency of anti-CBir1 was similar in patients with none versus at least 1 NOD2 variant, the quantitative response to CBir1 flagellin was significantly higher in patients with CD carrying at least 1 NOD2 variant versus those carrying no variants (median anti-CBir1 titer 33.39 versus 28.36, respectively; P = 0.01).


CONCLUSIONS
Anti-CBir1 serum reactivity in CD patients is independently associated with FS and complicated SB CD. Quantitative, but not qualitative, response to CBir1 is also significantly associated with the CD-associated NOD2 variants.
Papadakis
Konstantinos A
KA
Cedars-Sinai Inflammatory Bowel Disease Center, Los Angeles, California, USA. Papadakisk@cshs.org
Yang
Huiying
H
Ippoliti
Andrew
A
Mei
Ling
L
Elson
Charles O
CO
Hershberg
Robert M
RM
Vasiliauskas
Eric A
EA
Fleshner
Phillip R
PR
Abreu
Maria T
MT
Taylor
Kent
K
Landers
Carol J
CJ
Rotter
Jerome I
JI
Targan
Stephan R
SR
D000917:Antibody Formation; D000942:Antigens, Bacterial / Q000276:immunology*; D000946:Antigens, Fungal / Q000276:immunology; D003424:Crohn Disease / Q000235:genetics / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D005408:Flagellin / Q000276:immunology*; D006801:Humans; D007422:Intestines / Q000473:pathology; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D010641:Phenotype; D018272:Porins / Q000276:immunology; D012441:Saccharomyces cerevisiae / Q000276:immunology; D018089:Superantigens / Q000276:immunology
D000942:Antigens, Bacterial; D000946:Antigens, Fungal; C502160:CBir1 flagellin; D053473:Nod2 Signaling Adaptor Protein; C113724:OmpC protein; C469916:PfiT protein, Pseudomonas fluorescens; D018272:Porins; D018089:Superantigens; D005408:Flagellin