TY - JOUR
T1 - Combination of innate and adaptive immune alterations increased the likelihood of fibrostenosis in Crohn's disease
AU - Ippoliti, Andrew
AU - Devlin, Shane
AU - Mei, Ling
AU - Yang, Huiying
AU - Papadakis, Konstantinos A.
AU - Vasiliauskas, Eric A.
AU - McGovern, Dermot P.B.
AU - Abreu, Maria T.
AU - Melmed, Gil
AU - Shaye, Omid
AU - Enayati, Pedram
AU - Chen, Gary
AU - Choi, Jennifer
AU - Taylor, Kent
AU - Landers, Carol J.
AU - Rotter, Jerome I.
AU - Targan, Stephan R.
PY - 2010
Y1 - 2010
N2 - Background: Mutations in the nucleotide oligomerization domain-2 (NOD2) gene and positive antibodies to microbial antigens have been found to be associated with the Crohn's disease (CD) phenotype, fibrostenosis. The aim of this study was to confirm these relationships in a large cohort of CD patients and to determine the correlation between the presence of NOD2 variants and antibodies to oligomannan, CBir, outer membrane porin-C (OmpC), and I2 in CD patients with fibrostenosis. Methods: Sera and DNA from 731 unrelated CD patients were tested for NOD2 variants (SNP 8, 12, and 13) and the antibodies. The results were correlated with CD phenotypes, fibrostenosis, internal penetrating, perianal penetrating, and ulcerative colitis (UC)-like as well as other clinical features. Results: The presence of NOD2 allelic variants was primarily associated with fibrostenosis, secondarily with small bowel disease and small bowel surgery, and was inversely associated with UC-like disease. This association was present in patients with a fibrostenosis only (Vienna B2) and those with both stricturing and penetrating disease. The presence and level of antibodies to microbial antigens was also associated with the fibrostenosis phenotype. In the 316 patients with fibrostenosis the prevalence of NOD2 variants was significantly correlated with the antibody titer by quartile sum score. Further, when these patients with fibrostenosis were clustered by quartile sum score, the odds ratio for fibrostenosis was significantly higher in the patients with NOD2 variant alleles within each cluster, indicating synergy. Conclusions: Defects of innate (NOD2 variants) and adaptive (antibodies to microbial antigens) immunity act synergistically to increase the risk of the fibrostenosis phenotype.
AB - Background: Mutations in the nucleotide oligomerization domain-2 (NOD2) gene and positive antibodies to microbial antigens have been found to be associated with the Crohn's disease (CD) phenotype, fibrostenosis. The aim of this study was to confirm these relationships in a large cohort of CD patients and to determine the correlation between the presence of NOD2 variants and antibodies to oligomannan, CBir, outer membrane porin-C (OmpC), and I2 in CD patients with fibrostenosis. Methods: Sera and DNA from 731 unrelated CD patients were tested for NOD2 variants (SNP 8, 12, and 13) and the antibodies. The results were correlated with CD phenotypes, fibrostenosis, internal penetrating, perianal penetrating, and ulcerative colitis (UC)-like as well as other clinical features. Results: The presence of NOD2 allelic variants was primarily associated with fibrostenosis, secondarily with small bowel disease and small bowel surgery, and was inversely associated with UC-like disease. This association was present in patients with a fibrostenosis only (Vienna B2) and those with both stricturing and penetrating disease. The presence and level of antibodies to microbial antigens was also associated with the fibrostenosis phenotype. In the 316 patients with fibrostenosis the prevalence of NOD2 variants was significantly correlated with the antibody titer by quartile sum score. Further, when these patients with fibrostenosis were clustered by quartile sum score, the odds ratio for fibrostenosis was significantly higher in the patients with NOD2 variant alleles within each cluster, indicating synergy. Conclusions: Defects of innate (NOD2 variants) and adaptive (antibodies to microbial antigens) immunity act synergistically to increase the risk of the fibrostenosis phenotype.
KW - Crohn's disease
KW - Fibrostenosis
KW - NOD2
KW - Phenotype
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U2 - 10.1002/ibd.21196
DO - 10.1002/ibd.21196
M3 - Article
C2 - 20027650
AN - SCOPUS:77955738032
SN - 1078-0998
VL - 16
SP - 1279
EP - 1285
JO - Inflammatory bowel diseases
JF - Inflammatory bowel diseases
IS - 8
ER -