Genetic susceptibility to increased bacterial translocation influences the response to biological therapy in patients with Crohn's disease
Data(s) |
2013
|
---|---|
Resumo |
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: 179 patients with Crohn's disease were included. CD-related NOD2 and ATG16L1 variants were genotyped. Phagocytic and bactericidal activities were evaluated in blood neutrophils. Bacterial DNA, TNFα, IFNγ, IL-12p40, free serum infliximab/adalimumab levels and antidrug antibodies were measured. 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 |
Formato |
application/pdf |
Identificador |
http://boris.unibe.ch/53100/1/Genetic%20susceptibility%20to%20increased%20bacterial.pdf Gutierrez, A.; Scharl, M.; Sempere, L.; Holler, E.; Zapater, P.; Almenta, I.; Gonzalez-Navajas, J. M.; Such, J.; Wiest, Reiner; Rogler, G.; Frances, R. (2013). Genetic susceptibility to increased bacterial translocation influences the response to biological therapy in patients with Crohn's disease. Gut, 63(2), pp. 272-280. BMJ Publishing Group 10.1136/gutjnl-2012-303557 <http://dx.doi.org/10.1136/gutjnl-2012-303557> doi:10.7892/boris.53100 info:doi:10.1136/gutjnl-2012-303557 urn:issn:0017-5749 |
Idioma(s) |
eng |
Publicador |
BMJ Publishing Group |
Relação |
http://boris.unibe.ch/53100/ |
Direitos |
info:eu-repo/semantics/restrictedAccess |
Fonte |
Gutierrez, A.; Scharl, M.; Sempere, L.; Holler, E.; Zapater, P.; Almenta, I.; Gonzalez-Navajas, J. M.; Such, J.; Wiest, Reiner; Rogler, G.; Frances, R. (2013). Genetic susceptibility to increased bacterial translocation influences the response to biological therapy in patients with Crohn's disease. Gut, 63(2), pp. 272-280. BMJ Publishing Group 10.1136/gutjnl-2012-303557 <http://dx.doi.org/10.1136/gutjnl-2012-303557> |
Palavras-Chave | #610 Medicine & health |
Tipo |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion NonPeerReviewed |