NOD2 Variants and Antibody Response to Microbial Antigens in Crohn's Disease Patients and Their Unaffected Relatives

Shane M. Devlin, Huiying Yang, Andrew Ippoliti, Kent D. Taylor, Carol J. Landers, Xiaowen Su, Maria T Abreu, Konstantinos A. Papadakis, Eric A. Vasiliauskas, Gil Y. Melmed, Phillip R. Fleshner, Ling Mei, Jerome I. Rotter, Stephan R. Targan

Research output: Contribution to journalArticle

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Abstract

Background & Aims: The Cdcs1 locus of the C3Bir mouse confers severe colitis associated with a decrease in innate immune function and an increase in adaptive T-cell responses to commensal bacterial products. The aim of our study was to determine if defects in innate immunity are similarly associated with increased adaptive immune responses to microbial antigens in Crohn's disease patients. Methods: Sera from 732 patients, 220 unaffected relatives, and 200 healthy controls were tested for antibodies to oligomannan, the Pseudomonas fluorescens-related protein, Escherichia coli outer membrane porin C, CBir1 flagellin, and DNA from the same subjects was tested for 3 Crohn's disease-associated variants of the NOD2 gene, and 5 toll-like receptor (TLR) 2, 2 TLR4, and 2 TLR9 variants. The magnitude of responses to microbial antigens was examined according to variant status. Results: NOD2 variant carriage increased in frequency with increasing number of positive antibodies and increasing cumulative quantitative response as measured by quartile sum (P for trend, .0008 and .0003, respectively). Mean antibody and quartile sums were higher for patients carrying any NOD2 variant versus those carrying none (2.24 vs 1.92 and 10.60 vs 9.72; P = .0008 and P = 0.0003, respectively). The mean quartile sum was higher for unaffected relatives carrying any NOD2 variant versus those carrying none (10.67 vs 9.75, respectively; P = .02). No association was found between any TLR variant and the magnitude of response. Conclusions: Patients with Crohn's disease and unaffected relatives carrying variants of the NOD2 gene have increased adaptive immune responses to microbial antigens.

Original languageEnglish
Pages (from-to)576-586
Number of pages11
JournalGastroenterology
Volume132
Issue number2
DOIs
StatePublished - Feb 1 2007
Externally publishedYes

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Crohn Disease
Antibody Formation
Antigens
Adaptive Immunity
Antibodies
Toll-Like Receptor 2
Pseudomonas fluorescens
Porins
Toll-Like Receptors
Escherichia coli Proteins
Colitis
Innate Immunity
Genes
T-Lymphocytes
Membranes
DNA
Serum

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Devlin, S. M., Yang, H., Ippoliti, A., Taylor, K. D., Landers, C. J., Su, X., ... Targan, S. R. (2007). NOD2 Variants and Antibody Response to Microbial Antigens in Crohn's Disease Patients and Their Unaffected Relatives. Gastroenterology, 132(2), 576-586. https://doi.org/10.1053/j.gastro.2006.11.013

NOD2 Variants and Antibody Response to Microbial Antigens in Crohn's Disease Patients and Their Unaffected Relatives. / Devlin, Shane M.; Yang, Huiying; Ippoliti, Andrew; Taylor, Kent D.; Landers, Carol J.; Su, Xiaowen; Abreu, Maria T; Papadakis, Konstantinos A.; Vasiliauskas, Eric A.; Melmed, Gil Y.; Fleshner, Phillip R.; Mei, Ling; Rotter, Jerome I.; Targan, Stephan R.

In: Gastroenterology, Vol. 132, No. 2, 01.02.2007, p. 576-586.

Research output: Contribution to journalArticle

Devlin, SM, Yang, H, Ippoliti, A, Taylor, KD, Landers, CJ, Su, X, Abreu, MT, Papadakis, KA, Vasiliauskas, EA, Melmed, GY, Fleshner, PR, Mei, L, Rotter, JI & Targan, SR 2007, 'NOD2 Variants and Antibody Response to Microbial Antigens in Crohn's Disease Patients and Their Unaffected Relatives', Gastroenterology, vol. 132, no. 2, pp. 576-586. https://doi.org/10.1053/j.gastro.2006.11.013
Devlin, Shane M. ; Yang, Huiying ; Ippoliti, Andrew ; Taylor, Kent D. ; Landers, Carol J. ; Su, Xiaowen ; Abreu, Maria T ; Papadakis, Konstantinos A. ; Vasiliauskas, Eric A. ; Melmed, Gil Y. ; Fleshner, Phillip R. ; Mei, Ling ; Rotter, Jerome I. ; Targan, Stephan R. / NOD2 Variants and Antibody Response to Microbial Antigens in Crohn's Disease Patients and Their Unaffected Relatives. In: Gastroenterology. 2007 ; Vol. 132, No. 2. pp. 576-586.
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AU - Devlin, Shane M.

AU - Yang, Huiying

AU - Ippoliti, Andrew

AU - Taylor, Kent D.

AU - Landers, Carol J.

AU - Su, Xiaowen

AU - Abreu, Maria T

AU - Papadakis, Konstantinos A.

AU - Vasiliauskas, Eric A.

AU - Melmed, Gil Y.

AU - Fleshner, Phillip R.

AU - Mei, Ling

AU - Rotter, Jerome I.

AU - Targan, Stephan R.

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N2 - Background & Aims: The Cdcs1 locus of the C3Bir mouse confers severe colitis associated with a decrease in innate immune function and an increase in adaptive T-cell responses to commensal bacterial products. The aim of our study was to determine if defects in innate immunity are similarly associated with increased adaptive immune responses to microbial antigens in Crohn's disease patients. Methods: Sera from 732 patients, 220 unaffected relatives, and 200 healthy controls were tested for antibodies to oligomannan, the Pseudomonas fluorescens-related protein, Escherichia coli outer membrane porin C, CBir1 flagellin, and DNA from the same subjects was tested for 3 Crohn's disease-associated variants of the NOD2 gene, and 5 toll-like receptor (TLR) 2, 2 TLR4, and 2 TLR9 variants. The magnitude of responses to microbial antigens was examined according to variant status. Results: NOD2 variant carriage increased in frequency with increasing number of positive antibodies and increasing cumulative quantitative response as measured by quartile sum (P for trend, .0008 and .0003, respectively). Mean antibody and quartile sums were higher for patients carrying any NOD2 variant versus those carrying none (2.24 vs 1.92 and 10.60 vs 9.72; P = .0008 and P = 0.0003, respectively). The mean quartile sum was higher for unaffected relatives carrying any NOD2 variant versus those carrying none (10.67 vs 9.75, respectively; P = .02). No association was found between any TLR variant and the magnitude of response. Conclusions: Patients with Crohn's disease and unaffected relatives carrying variants of the NOD2 gene have increased adaptive immune responses to microbial antigens.

AB - Background & Aims: The Cdcs1 locus of the C3Bir mouse confers severe colitis associated with a decrease in innate immune function and an increase in adaptive T-cell responses to commensal bacterial products. The aim of our study was to determine if defects in innate immunity are similarly associated with increased adaptive immune responses to microbial antigens in Crohn's disease patients. Methods: Sera from 732 patients, 220 unaffected relatives, and 200 healthy controls were tested for antibodies to oligomannan, the Pseudomonas fluorescens-related protein, Escherichia coli outer membrane porin C, CBir1 flagellin, and DNA from the same subjects was tested for 3 Crohn's disease-associated variants of the NOD2 gene, and 5 toll-like receptor (TLR) 2, 2 TLR4, and 2 TLR9 variants. The magnitude of responses to microbial antigens was examined according to variant status. Results: NOD2 variant carriage increased in frequency with increasing number of positive antibodies and increasing cumulative quantitative response as measured by quartile sum (P for trend, .0008 and .0003, respectively). Mean antibody and quartile sums were higher for patients carrying any NOD2 variant versus those carrying none (2.24 vs 1.92 and 10.60 vs 9.72; P = .0008 and P = 0.0003, respectively). The mean quartile sum was higher for unaffected relatives carrying any NOD2 variant versus those carrying none (10.67 vs 9.75, respectively; P = .02). No association was found between any TLR variant and the magnitude of response. Conclusions: Patients with Crohn's disease and unaffected relatives carrying variants of the NOD2 gene have increased adaptive immune responses to microbial antigens.

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