Genetic susceptibility to increased bacterial translocation influences the response to biological therapy in patients with Crohn's disease

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

[img] Text
Genetic susceptibility to increased bacterial.pdf - Published Version
Restricted to registered users only
Available under License Publisher holds Copyright.

Download (1MB) | Request a copy

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

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Gastroenterology

UniBE Contributor:

Wiest, Reiner

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0017-5749

Publisher:

BMJ Publishing Group

Language:

English

Submitter:

Lilian Karin Smith-Wirth

Date Deposited:

13 Jun 2014 12:19

Last Modified:

06 Nov 2015 09:57

Publisher DOI:

10.1136/gutjnl-2012-303557

Uncontrolled Keywords:

Bacterial Translocation, Crohn'S Disease, Ibd - Genetics, Immune Response, Infliximab

BORIS DOI:

10.7892/boris.53100

URI:

https://boris.unibe.ch/id/eprint/53100

Actions (login required)

Edit item Edit item
Provide Feedback