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. 2010 Aug;16(8):1279-85.
doi: 10.1002/ibd.21196.

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

Andrew Ippoliti  1 , Shane Devlin, Ling Mei, Huiying Yang, Konstantinos A Papadakis, Eric A Vasiliauskas, Dermot P B McGovern, Maria T Abreu, Gil Melmed, Omid Shaye, Pedram Enayati, Gary Chen, Jennifer Choi, Kent Taylor, Carol J Landers, Jerome I Rotter, Stephan R Targan
Affiliations

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

Andrew Ippoliti et al. Inflamm Bowel Dis. 2010 Aug.

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.

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Figures

FIGURE 1
FIGURE 1
The prevalence of the fibrostenosis in patients with 0, 1, 2, 3, or 4 positive antibodies to oligomannan, CBir, OmpC, or I2 in the 731 CD patients. The probability was significant for trend, P < 0.0001. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]
FIGURE 2
FIGURE 2
The prevalence of fibrostenosis in patients grouped according to the quartile sum score for antibodies to oligomannan, CBir, OmpC, or I2 in the 731 CD patients. The probability was significant for trend, P < 0.0001. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]
FIGURE 3
FIGURE 3
The prevalence of NOD2 variant alleles in the 316 patients with fibrostenosis is described. (A) The prevalence for NOD2 variants is compared with the number of positive antibodies (antibody sums) (P for trend = 0.059). (B) The prevalence is compared with the quartile sum scores, clustered 4–6, 7–9, 10–13, 14–16 (P for trend < 0.001). [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]
FIGURE 4
FIGURE 4
This schematic diagram depicts the association between innate and adaptive immune responses in CD in general and their synergistic effect in fibrostenosis.
See this image and copyright information in PMC

References

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