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

Andrew Ippoliti, Shane Devlin, Ling Mei, Huiying Yang, Konstantinos 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

Research output: Contribution to journalArticle

23 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1279-1285
Number of pages7
JournalInflammatory Bowel Diseases
Volume16
Issue number8
DOIs
StatePublished - Aug 24 2010
Externally publishedYes

Fingerprint

Crohn Disease
Nucleotides
Antibodies
Phenotype
Ulcerative Colitis
Antigens
Porins
Single Nucleotide Polymorphism
Immunity
Alleles
Odds Ratio
Mutation
Membranes
DNA
Serum
Genes

Keywords

  • Crohn's disease
  • Fibrostenosis
  • NOD2
  • Phenotype

ASJC Scopus subject areas

  • Immunology and Allergy
  • Gastroenterology

Cite this

Combination of innate and adaptive immune alterations increased the likelihood of fibrostenosis in Crohn's disease. / Ippoliti, Andrew; Devlin, Shane; Mei, Ling; Yang, Huiying; Papadakis, Konstantinos; Vasiliauskas, Eric A.; McGovern, Dermot P.B.; Abreu, Maria T.; Melmed, Gil; Shaye, Omid; Enayati, Pedram; Chen, Gary; Choi, Jennifer; Taylor, Kent; Landers, Carol J.; Rotter, Jerome I.; Targan, Stephan R.

In: Inflammatory Bowel Diseases, Vol. 16, No. 8, 24.08.2010, p. 1279-1285.

Research output: Contribution to journalArticle

Ippoliti, A, Devlin, S, Mei, L, Yang, H, Papadakis, K, Vasiliauskas, EA, McGovern, DPB, Abreu, MT, Melmed, G, Shaye, O, Enayati, P, Chen, G, Choi, J, Taylor, K, Landers, CJ, Rotter, JI & Targan, SR 2010, 'Combination of innate and adaptive immune alterations increased the likelihood of fibrostenosis in Crohn's disease', Inflammatory Bowel Diseases, vol. 16, no. 8, pp. 1279-1285. https://doi.org/10.1002/ibd.21196
Ippoliti, Andrew ; Devlin, Shane ; Mei, Ling ; Yang, Huiying ; Papadakis, Konstantinos ; Vasiliauskas, Eric A. ; McGovern, Dermot P.B. ; Abreu, Maria T. ; Melmed, Gil ; Shaye, Omid ; Enayati, Pedram ; Chen, Gary ; Choi, Jennifer ; Taylor, Kent ; Landers, Carol J. ; Rotter, Jerome I. ; Targan, Stephan R. / Combination of innate and adaptive immune alterations increased the likelihood of fibrostenosis in Crohn's disease. In: Inflammatory Bowel Diseases. 2010 ; Vol. 16, No. 8. pp. 1279-1285.
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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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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

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.

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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

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KW - Phenotype

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