title: Association of anti-idiotypic antibodies with immune tolerance induction for the treatment of hemophilia A with inhibitors.
abstract: OBJECTIVE
  Hemophilia A patients with inhibitors can be treated effectively with immune tolerance induction therapy (ITI). One of the underlying mechanisms of ITI is conceived to be a neutralizing activity of anti-idiotypic antibodies on inhibitors. The goal of the present study was to develop an uncomplicated method for assessing antiidiotypic antibodies and to prove the advent of anti-idiotypic antibodies in ITI.
  
  
  METHODS
  We studied a total of 26 plasma samples obtained from 9 hemophilic inhibitor patients who were treated with ITI. The samples were investigated with a novel method for detecting anti-idiotypic antibodies based on a liquid phase blocking immunoprecipitation.
  
  
  RESULTS
  Plasma anti-factor VIII (FVIII) antibody titer was reduced by adding plasma from patients who had received completely successful ITI. This anti-FVIII antibody-neutralization activity of the plasma was impaired by treating the plasma with protein G beads. In addition, treating inhibitor plasma from patients in whom ITI had been unsuccessful with FVIII affinity beads resulted in the development of the anti-FVIII antibody-neutralization activity. Furthermore, the anti-FVIII antibody-neutralization activity of anti-FVIII antibody-depleted plasma obtained in a late period of ITI on inhibitor plasmas obtained during ITI increased over time.
  
  
  CONCLUSIONS
  Our results suggest that; (i) plasma from patients in whom ITI was completely successful contained an anti-FVIII antibody-neutralization factor; (ii) the anti-FVIII antibody-neutralization factor was in the IgG fraction (i.e., the factor would be anti-idiotypic antibodies), and (iii) anti-idiotypic antibodies existed even in plasma from patients in whom ITI was unsuccessful. Our observations support the notion that the mechanism of ITI is associated with the development of anti-idiotypic antibodies.
authors.affiliation: Department of Pediatrics, Nara Medical University, Nara, Japan. ysakurai@naramed-u.ac.jp
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Sakurai
authors.forename: Midori
authors.initials: M
authors.lastname: Shima
authors.forename: Ichiro
authors.initials: I
authors.lastname: Tanaka
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Fukuda
authors.forename: Koichi
authors.initials: K
authors.lastname: Yoshida
authors.forename: Akira
authors.initials: A
authors.lastname: Yoshioka
mesh_terms: D000888:Antibodies, Anti-Idiotypic / Q000097:blood* / Q000276:immunology; D000917:Antibody Formation; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D005169:Factor VIII / Q000276:immunology; D006467:Hemophilia A / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*
chemical_list: D000888:Antibodies, Anti-Idiotypic; D001323:Autoantibodies; D005169:Factor VIII