Abstract | OBJECTIVE: The aetiology of Crohn's disease (CD) has been related to nucleotide-binding oligomerisation domain containing 2 (NOD2) and ATG16L1 gene variants. The observation of bacterial DNA translocation in patients with CD led us to hypothesise that this process may be facilitated in patients with NOD2/ATG16L1-variant genotypes, affecting the efficacy of anti-tumour necrosis factor (TNF) therapies. DESIGN: RESULTS:
Bacterial DNA was found in 44% of patients with active disease versus 23% of patients with remitting disease (p=0.01). A NOD2-variant or ATG16L1-variant genotype was associated with bacterial DNA presence (OR 4.8; 95% CI 1.1 to 13.2; p=0.001; and OR 2.4; 95% CI 1.4 to 4.7; p=0.01, respectively). This OR was 12.6 (95% CI 4.2 to 37.8; p=0.001) for patients with a double-variant genotype. Bacterial DNA was associated with disease activity (OR 2.6; 95% CI 1.3 to 5.4; p=0.005). Single and double-gene variants were not associated with disease activity (p=0.19). 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. CONCLUSIONS: Our results characterise a subgroup of patients with CD who may require a more aggressive therapy to reduce the extent of inflammation and the risk of relapse.
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Authors | Ana Gutiérrez, Michael Scharl, Laura Sempere, Ernst Holler, Pedro Zapater, Isabel Almenta, José M González-Navajas, José Such, Reiner Wiest, Gerhard Rogler, Rubén Francés |
Journal | Gut
(Gut)
Vol. 63
Issue 2
Pg. 272-80
(Feb 2014)
ISSN: 1468-3288 [Electronic] England |
PMID | 23376290
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- ATG16L1 protein, human
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Humanized
- Autophagy-Related Proteins
- Carrier Proteins
- DNA, Bacterial
- Interleukin-12 Subunit p40
- Nod2 Signaling Adaptor Protein
- Peptide Fragments
- Tumor Necrosis Factor-alpha
- interferon gamma (1-39)
- Interferon-gamma
- Infliximab
- Adalimumab
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Topics |
- Adalimumab
- Adult
- Antibodies, Monoclonal
(blood, therapeutic use)
- Antibodies, Monoclonal, Humanized
(blood, therapeutic use)
- Autophagy-Related Proteins
- Bacterial Translocation
(physiology)
- Biological Therapy
(methods)
- Carrier Proteins
(genetics)
- Crohn Disease
(drug therapy, microbiology)
- DNA, Bacterial
(genetics)
- Female
- Genetic Predisposition to Disease
- Genotype
- Humans
- Infliximab
- Interferon-gamma
(blood)
- Interleukin-12 Subunit p40
(blood)
- Male
- Middle Aged
- Nod2 Signaling Adaptor Protein
(genetics)
- Peptide Fragments
(blood)
- Recurrence
- Treatment Outcome
- Tumor Necrosis Factor-alpha
(antagonists & inhibitors)
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