Article

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

Department of Surgery, Cedars-Sinai Medical Center, Los Ángeles, California, United States
Gastroenterology (Impact Factor: 13.93). 02/2007; 132(2):576-86. DOI: 10.1053/j.gastro.2006.11.013
Source: PubMed

ABSTRACT 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.
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.
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.
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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    • "However, recently [40] [41] [42] [43] polymorphisms of this gene, like R702W, G908R, and L1007finsC, were found to confer a predisposition to anti-microbial antibodies development. Furthermore, Devlin et al. [25] demonstrated that both in Crohn's disease patients and their unaffected relatives carrying any NOD2 variant, the number of positive antibodies and their semi-quantitative levels were higher than in those with no variants. It is therefore possible that relatives, who share the same genetic background, are more prone to develop anti-microbial antibodies. "
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    • "The present data further support this opinion. In addition, this excess of yeast and bacteria translocation through PP of KO mice is in agreement with recent reports showing that mutated CD patients and their unaffected relatives develop more frequently antibodies to Saccharomyces cerevisiae, Pseudomonas fluorescens–related protein, Escherichia coli outer membrane porin C and CBir1 flagellin [38]. The excessive bacteria and yeast passage reported here may participate in the enhancement of adaptive immune responses to microbial antigens. "
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