Exploring the binding sites of anti-infliximab antibodies in pediatric patients with rheumatic diseases treated with infliximab

Pediatr Res. 2011 Mar;69(3):243-8. doi: 10.1203/PDR.0b013e318208451d.


Over the past decade, the treatment of a variety of immune-mediated diseases has improved greatly due to the introduction of biologics for therapies in cases that are nonresponsive to traditional treatments. However, a side effect not encountered in traditional treatments is the immunogenicity of the biologics themselves. Our aim was to investigate the anti-infliximab-antibody response in pediatric patients receiving infliximab for juvenile idiopathic arthritis and other pediatric rheumatic diseases, with a focus on an analysis of the binding sites of these antibodies. We show that anti-infliximab antibodies developed in 43% of patients receiving infliximab therapy. Neutralization studies showed that in all these patients, the antibodies were directed toward the variable domains of infliximab, as they inhibited binding of infliximab to TNF. A more precise determination of the antibody epitopes using synthetic peptides was not achieved, indicating that all the antibody binding sites were composed of discontinuous segments of infliximab.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antibodies / blood
  • Antibodies / immunology*
  • Antibodies, Monoclonal / blood
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / immunology*
  • Antibodies, Monoclonal / therapeutic use*
  • Antirheumatic Agents / blood
  • Antirheumatic Agents / chemistry
  • Antirheumatic Agents / immunology*
  • Antirheumatic Agents / therapeutic use*
  • Binding Sites
  • Child
  • Child, Preschool
  • Epitopes
  • Female
  • Humans
  • Immunoglobulin G / immunology
  • Infliximab
  • Protein Conformation
  • Rheumatic Diseases / blood
  • Rheumatic Diseases / drug therapy*
  • Rheumatic Diseases / immunology*


  • Antibodies
  • Antibodies, Monoclonal
  • Antirheumatic Agents
  • Epitopes
  • Immunoglobulin G
  • Infliximab