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 antic 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 12, 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 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 antiCBir1 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.