title: Development of a new immunoassay for the accurate determination of anti-infliximab antibodies in inflammatory bowel disease.
abstract: BACKGROUND
  The formation of antibodies to infliximab (ATIs) is closely associated with the loss of response to infliximab in patients with inflammatory bowel disease (IBD). We evaluated the clinical utility of a novel method to measure serum ATI levels in the presence of infliximab.
  
  
  METHODS
  ATI levels were measured using a novel immunoassay and the conventional method in 58 patients with Crohn's disease (CD) under infliximab maintenance therapy. The serum infliximab trough levels were determined by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  ATIs were detected in 16 out of 58 patients (27.6%) by the new method, but the conventional method detected only 2 patients (3.4%) who had the two highest ATI titers assayed by the new method. The presence of ATIs in the samples positive by the new method but negative by the conventional method was confirmed by Western blot analysis. Western blotting analysis also indicated that the new method could restore the binding capacities of the ATIs whose recognition sites were occupied by free infliximab. In the new method, the addition of infliximab to the samples dose-dependently blocked the detection of ATIs. Patients positive for ATIs had significantly lower serum trough levels of infliximab (P < 0.01) and significantly higher clinical activity scores (P < 0.001) as compared with patients negative for ATI.
  
  
  CONCLUSIONS
  The new method makes it possible to measure serum ATI levels in the presence of infliximab. This method is useful for deciding the optimal management strategies for IBD patients with loss of response to infliximab.
authors.affiliation: Department of Medicine, Shiga University of Medical Science, Seta-Tukinowa, Otsu 520-2192, Japan.
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Imaeda
authors.forename: Akira
authors.initials: A
authors.lastname: Andoh
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Fujiyama
mesh_terms: D000328:Adult; D000906:Antibodies / Q000097:blood*; D000911:Antibodies, Monoclonal / Q000097:blood / Q000276:immunology* / Q000627:therapeutic use*; D015153:Blotting, Western; D003424:Crohn Disease / Q000188:drug therapy* / Q000276:immunology*; D005260:Female; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D017211:Treatment Failure; D055815:Young Adult
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D000069285:Infliximab