NOD2/CARD15 does not influence response to infliximab in Crohn's disease

Gastroenterology. 2002 Jul;123(1):106-11. doi: 10.1053/gast.2002.34172.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal / therapeutic use*
  • Carrier Proteins / genetics*
  • Cohort Studies
  • Crohn Disease / drug therapy*
  • Crohn Disease / genetics*
  • Crohn Disease / metabolism
  • Female
  • Gastrointestinal Agents / therapeutic use*
  • Gene Frequency
  • Genotype
  • Humans
  • Infliximab
  • Intracellular Signaling Peptides and Proteins*
  • Male
  • Nod2 Signaling Adaptor Protein
  • Predictive Value of Tests
  • Reference Values
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / biosynthesis


  • Antibodies, Monoclonal
  • Carrier Proteins
  • Gastrointestinal Agents
  • Intracellular Signaling Peptides and Proteins
  • NOD2 protein, human
  • Nod2 Signaling Adaptor Protein
  • Tumor Necrosis Factor-alpha
  • Infliximab