NOD2, CD14 and TLR4 mutations do not influence response to adalimumab in patients with Crohn's disease: a preliminary report

Rev Esp Enferm Dig. 2010 Oct;102(10):591-5. doi: 10.4321/s1130-01082010001000005.

Abstract

Introduction: Adalimumab is a recombinant fully-human monoclonal immunoglobulin (IgG1) antibody utilized in the treatment of Crohn's disease. Unfortunately no clinical or genetic markers exist to predict response to anti-tumor necrosis factor-alpha (TNF) therapy. The aim of this study was to evaluate the association between selected genes involved in cytokine regulation and response to adalimumab treatment in Crohn's disease.

Methods: twenty-four patients with Crohn's disease either naïve (n = 8) or had lost response or were unable to tolerate the chimeric anti-TNF antibody infliximab (n=16) were enrolled in the study. Patients were genotyped for main polymorphisms in NOD2, CD14 and TLR4 genes. Response to adalimumab treatment was defined as a decrease of Crohn's disease activity index of at least 100 points or a closure of at least 50% of fistulas in case of fistulizing Crohn's disease.

Results: overall, 75% of patients did respond to treatment. However, no statistically significant association was found between any of the genotypes and the response to adalimumab.

Conclusions: In our small study group no association between the studied polymorphisms and response to adalimumab was apparent. Systematic studies to search for genetic markers of response to anti-TNF therapy are necessary.

MeSH terms

  • Adalimumab
  • Adult
  • Age of Onset
  • Anti-Inflammatory Agents / therapeutic use*
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Crohn Disease / drug therapy*
  • Crohn Disease / genetics*
  • Cytokines / metabolism
  • Female
  • Genetic Markers
  • Genotype
  • Humans
  • Lipopolysaccharide Receptors / genetics*
  • Male
  • Middle Aged
  • Nod2 Signaling Adaptor Protein / genetics*
  • Polymorphism, Single Nucleotide
  • Reverse Transcriptase Polymerase Chain Reaction
  • Toll-Like Receptor 4 / genetics*

Substances

  • Anti-Inflammatory Agents
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Cytokines
  • Genetic Markers
  • Lipopolysaccharide Receptors
  • NOD2 protein, human
  • Nod2 Signaling Adaptor Protein
  • Toll-Like Receptor 4
  • Adalimumab