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

✍ Scribed by Konstantinos A. 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

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 149 KB
• Volume: 13
• Category: Article
• ISSN: 1078-0998
• DOI: 10.1002/ibd.20106

✦ Synopsis

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 ϭ 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.