| NOD2/CARD15 does not influence response to infliximab in Crohn's disease. | |
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MedLine Citation:
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PMID: 12105838 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND & AIMS: NOD2/CARD15 was recently identified as the first gene underlying Crohn's disease (CD) susceptibility. Monoclonal antibodies to tumor necrosis factor (TNF)-alpha (infliximab) are a potent treatment for CD, with about 70% of patients responding. It is not clear which factors influence treatment outcome. We assessed whether variants in NOD2/CARD15 are predictive for differences in clinical response. METHODS: Two hundred forty-five CD patients (86 fistulizing, 159 luminal) receiving infliximab in an expanded access program were genotyped for the 3 main associated variants of NOD2/CARD15, without knowledge of the treatment response. Short-term clinical response was assessed at 4 weeks (refractory) or 10 weeks (fistulizing) after first infliximab infusion, and the mean duration of response was calculated. In a subgroup of patients, production of TNF in response to lipopolysaccharide (LPS) in mucosal biopsy tissue was also determined by means of immunoassay, and results were related to the different NOD2/CARD15 genotypes. RESULTS: In total, 32.6% of patients carried mutations in NOD2/CARD15 (18.8% R702W, 8.6% G908R, and 10.2% 1007fs) compared with 15% in controls (P < 0.001). Despite observed differences in TNF production in mucosal biopsy tissue, there was no relationship between the overall presence of a mutation in NOD2/CARD15 or of any of the mutations separately and short-term infliximab response or response duration. Furthermore, multivariate analysis could not identify clinical characteristics that, in combination with NOD2/CARD15 mutations, were associated with response to infliximab. CONCLUSIONS: In this cohort of CD patients, the frequency of NOD2/CARD15 mutations was significantly greater than that of healthy controls. However, NOD2/CARD15 was not predictive of treatment outcome with infliximab in CD. |
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Authors:
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Severine Vermeire; Edouard Louis; Paul Rutgeerts; Martine De Vos; Andre Van Gossum; Jacques Belaiche; Paul Pescatore; Rene Fiasse; Paul Pelckmans; Robert Vlietinck; Françoise Merlin; Habib Zouali; Gilles Thomas; Jean-Frederic Colombel; Jean-Pierre Hugot; |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Gastroenterology Volume: 123 ISSN: 0016-5085 ISO Abbreviation: Gastroenterology Publication Date: 2002 Jul |
Date Detail:
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Created Date: 2002-07-09 Completed Date: 2002-08-16 Revised Date: 2008-05-13 |
Medline Journal Info:
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Nlm Unique ID: 0374630 Medline TA: Gastroenterology Country: United States |
Other Details:
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Languages: eng Pagination: 106-11 Citation Subset: AIM; IM |
Affiliation:
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Department of Gastroenterology, UZ Gasthuisberg, Leuven, Belgium. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Antibodies, Monoclonal / therapeutic use* Carrier Proteins / genetics* Cohort Studies Crohn Disease / drug therapy*, genetics*, metabolism Female Gastrointestinal Agents / therapeutic use* Gene Frequency Genotype Humans Intracellular Signaling Peptides and Proteins* Male Nod2 Signaling Adaptor Protein Predictive Value of Tests Reference Values Treatment Outcome Tumor Necrosis Factor-alpha / biosynthesis |
| Chemical | |
Reg. No./Substance:
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0/Antibodies, Monoclonal; 0/Carrier Proteins; 0/Gastrointestinal Agents; 0/Intracellular Signaling Peptides and Proteins; 0/NOD2 protein, human; 0/Nod2 Signaling Adaptor Protein; 0/Tumor Necrosis Factor-alpha; 0/infliximab |
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