The etiology of Crohn's disease (CD) has been related to nucleotide-binding oligomerization domain containing 2 (NOD2) and ATG16L1 gene variants.
The observation of bacterial DNA translocation in patients with CD led researchers to hypothesize that this process may be facilitated in patients with NOD2/ATG16L1-variant genotypes, affecting the efficacy of anti-tumor necrosis factor (TNF) therapies.
Dr Ana Gutiérrez and colleagues evaluated 179 patients with Crohn's disease.
CD-related NOD2 and ATG16L1 variants were genotyped.
Phagocytic and bactericidal activities were evaluated in blood neutrophils.
|Bacterial DNA was found in 44% of patients with active disease |
Bacterial DNA, TNFα, IFNγ, IL-12p40, free serum infliximab/adalimumab levels and antidrug antibodies were measured.
The team found bacterial DNA in 44% of patients with active disease versus 23% of patients with remitting disease.
A NOD2-variant or ATG16L1-variant genotype was associated with bacterial DNA presence.
This OR was 13 for patients with a double-variant genotype.
The researchers observed bacterial DNA was associated with disease activity.
Single and double-gene variants were not associated with disease activity.
The team found that patients with a NOD2-variant genotype showed decreased phagocytic and bactericidal activities in blood neutrophils, increased TNFα levels in response to bacterial DNA and decreased trough levels of free anti-TNFα.
The proportion of patients on an intensified biological therapy was significantly higher in the NOD2-variant groups.
Dr Gutiérrez's team commented, "Our results characterize a subgroup of patients with CD who may require a more aggressive therapy to reduce the extent of inflammation and the risk of relapse."