Recently, it has been highlighted that three genetic markers, NOD2, MHC and MST1, were associated to distinct CD sites, supporting the concept that genetic variations may contribute to localize CD.
The purpose of this study was to perform a meta-analysis to determine the effect of NOD2/CARD15 polymorphisms on treatment response in patients with CD.
NOD2, the first gene associated to increased susceptibility to Crohn's disease, is a cytosolic receptor that senses wall peptides of bacteria and promotes their clearance through initiation of a proinflammatory transcriptional program.
By means of flow cytometry, production of tumor necrosis factor-alpha (TNF-α) was measured in peripheral blood monocytes from patients suffering from CD, ulcerative colitis (UC) and in healthy subjects after stimulation of the NOD2 and TLR pathways.
The most predominant link to the onset of CD is a genetic mutation in the innate immune receptor nucleotide-binding oligomerization domain-containing 2 (NOD2).
These results provide evidence that Crohn's disease patients have an impairment in MBL-MASP functional activity and that this defect is associated with MBL2 and NOD2 variants.
Anti-TNF-alpha loss of response is associated with a decreased percentage of FoxP3+ T cells and a variant NOD2 genotype in patients with Crohn's disease.
The aim of the present study was to investigate the genetic polymorphisms of the autophagy-associated genes autophagy-related 16-like 1 (ATG16L1), immunity-related GTPase M (IRGM), Unc-51-like kinase 1 (ULK1), and NOD2 with respect to early-onset Crohn disease (CD) among Korean children.
This finding, which links the decrease of human enteric antimicrobial peptides to increased NOD2 in ileal CD patients, provides a new view into the pathogenesis of ileal CD.
None of the patients with orofacial granulomatosis carried any of the NOD2 variations, whereas four of the 12 patients with coexisting Crohn's disease had a NOD2 variant (Arg702Trp).
As expected, the three NOD2 variants showed a significant association with CD but did not reach statistical significance, despite the fact that the allele frequency of NOD2 variants was in the range found in most of the European populations.
The presence of Crohn's-associated variants of NOD2 and ATG16L genes appears to be associated not only with alterations of mucosal barrier functions, and bacterial killing, but the gut microbiota, as well, reflecting a potential relationship between the host's genotype and intestinal dysbiosis, involved in disease etiology.
Since NOD2 is over-expressed in CD and mutant NOD2cannot result in NF-κB activity, our finding can provide an explanation of the previous observation showing decreased expression of human enteric α-defensin in CD and even more so in the presence of NOD2 mutations.
For CD patients, laboratory data were correlated with clinical phenotype, use of immunomodulation, and CD risk alleles (NOD2, IL-23R, ATG16L1 and IRGM).