Anti-flagellin (CBir1) phenotypic and genetic Crohn's disease associations

Konstantinos Papadakis, Huiying Yang, Andrew Ippoliti, Ling Mei, Charles O. Elson, Robert M. Hershberg, Eric A. Vasiliauskas, Phillip R. Fleshner, Maria T. Abreu, Kent Taylor, Carol J. Landers, Jerome I. Rotter, Stephan R. Targan

Research output: Contribution to journalArticle

89 Citations (Scopus)

Abstract

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 analysts showed that anti-CBir1 was independently associated with FS and UC-like CD irrespective of the antibody reactivity to 12, 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.

Original languageEnglish (US)
Pages (from-to)524-530
Number of pages7
JournalInflammatory Bowel Diseases
Volume13
Issue number5
DOIs
StatePublished - May 1 2007
Externally publishedYes

Fingerprint

Inborn Genetic Diseases
Crohn Disease
Ulcerative Colitis
Porins
Phenotype
CBir1 flagellin
Antigens
Membranes
Antibodies
Serum
Logistic Models

Keywords

  • Clinical phenotypes
  • Colitis
  • Crohn's disease
  • Flagellin

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Papadakis, K., Yang, H., Ippoliti, A., Mei, L., Elson, C. O., Hershberg, R. M., ... Targan, S. R. (2007). Anti-flagellin (CBir1) phenotypic and genetic Crohn's disease associations. Inflammatory Bowel Diseases, 13(5), 524-530. https://doi.org/10.1002/ibd.20106

Anti-flagellin (CBir1) phenotypic and genetic Crohn's disease associations. / Papadakis, Konstantinos; Yang, Huiying; Ippoliti, Andrew; Mei, Ling; Elson, Charles O.; Hershberg, Robert M.; Vasiliauskas, Eric A.; Fleshner, Phillip R.; Abreu, Maria T.; Taylor, Kent; Landers, Carol J.; Rotter, Jerome I.; Targan, Stephan R.

In: Inflammatory Bowel Diseases, Vol. 13, No. 5, 01.05.2007, p. 524-530.

Research output: Contribution to journalArticle

Papadakis, K, Yang, H, Ippoliti, A, Mei, L, Elson, CO, Hershberg, RM, Vasiliauskas, EA, Fleshner, PR, Abreu, MT, Taylor, K, Landers, CJ, Rotter, JI & Targan, SR 2007, 'Anti-flagellin (CBir1) phenotypic and genetic Crohn's disease associations', Inflammatory Bowel Diseases, vol. 13, no. 5, pp. 524-530. https://doi.org/10.1002/ibd.20106
Papadakis, Konstantinos ; Yang, Huiying ; Ippoliti, Andrew ; Mei, Ling ; Elson, Charles O. ; Hershberg, Robert M. ; Vasiliauskas, Eric A. ; Fleshner, Phillip R. ; Abreu, Maria T. ; Taylor, Kent ; Landers, Carol J. ; Rotter, Jerome I. ; Targan, Stephan R. / Anti-flagellin (CBir1) phenotypic and genetic Crohn's disease associations. In: Inflammatory Bowel Diseases. 2007 ; Vol. 13, No. 5. pp. 524-530.
@article{a782dd6ec39043e1bb8d310f5fd15cc7,
title = "Anti-flagellin (CBir1) phenotypic and genetic Crohn's disease associations",
abstract = "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 analysts showed that anti-CBir1 was independently associated with FS and UC-like CD irrespective of the antibody reactivity to 12, 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.",
keywords = "Clinical phenotypes, Colitis, Crohn's disease, Flagellin",
author = "Konstantinos Papadakis and Huiying Yang and Andrew Ippoliti and Ling Mei and Elson, {Charles O.} and Hershberg, {Robert M.} and Vasiliauskas, {Eric A.} and Fleshner, {Phillip R.} and Abreu, {Maria T.} and Kent Taylor and Landers, {Carol J.} and Rotter, {Jerome I.} and Targan, {Stephan R.}",
year = "2007",
month = "5",
day = "1",
doi = "10.1002/ibd.20106",
language = "English (US)",
volume = "13",
pages = "524--530",
journal = "Inflammatory Bowel Diseases",
issn = "1078-0998",
publisher = "John Wiley and Sons Inc.",
number = "5",

}

TY - JOUR

T1 - Anti-flagellin (CBir1) phenotypic and genetic Crohn's disease associations

AU - Papadakis, Konstantinos

AU - Yang, Huiying

AU - Ippoliti, Andrew

AU - Mei, Ling

AU - Elson, Charles O.

AU - Hershberg, Robert M.

AU - Vasiliauskas, Eric A.

AU - Fleshner, Phillip R.

AU - Abreu, Maria T.

AU - Taylor, Kent

AU - Landers, Carol J.

AU - Rotter, Jerome I.

AU - Targan, Stephan R.

PY - 2007/5/1

Y1 - 2007/5/1

N2 - 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 analysts showed that anti-CBir1 was independently associated with FS and UC-like CD irrespective of the antibody reactivity to 12, 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.

AB - 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 analysts showed that anti-CBir1 was independently associated with FS and UC-like CD irrespective of the antibody reactivity to 12, 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.

KW - Clinical phenotypes

KW - Colitis

KW - Crohn's disease

KW - Flagellin

UR - http://www.scopus.com/inward/record.url?scp=33847664069&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33847664069&partnerID=8YFLogxK

U2 - 10.1002/ibd.20106

DO - 10.1002/ibd.20106

M3 - Article

C2 - 17260364

AN - SCOPUS:33847664069

VL - 13

SP - 524

EP - 530

JO - Inflammatory Bowel Diseases

JF - Inflammatory Bowel Diseases

SN - 1078-0998

IS - 5

ER -