TY - JOUR
T1 - NOD2 Variants and Antibody Response to Microbial Antigens in Crohn's Disease Patients and Their Unaffected Relatives
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.
N1 - Funding Information:
Supported by National Institutes of Health grant PO1 DK46763.
PY - 2007/2
Y1 - 2007/2
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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U2 - 10.1053/j.gastro.2006.11.013
DO - 10.1053/j.gastro.2006.11.013
M3 - Article
C2 - 17258734
AN - SCOPUS:33847016160
SN - 0016-5085
VL - 132
SP - 576
EP - 586
JO - Gastroenterology
JF - Gastroenterology
IS - 2
ER -