Combination of innate and adaptive immune alterations increased the likelihood of fibrostenosis in Crohn's disease.

Abstract:

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.

journal_name

Inflamm Bowel Dis

authors

Ippoliti A,Devlin S,Mei L,Yang H,Papadakis KA,Vasiliauskas EA,McGovern DP,Abreu MT,Melmed G,Shaye O,Enayati P,Chen G,Choi J,Taylor K,Landers CJ,Rotter JI,Targan SR

doi

10.1002/ibd.21196

subject

Has Abstract

pub_date

2010-08-01 00:00:00

pages

1279-85

issue

8

eissn

1078-0998

issn

1536-4844

journal_volume

16

pub_type

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