title: Incidence and disease associations of a proteinase 3-antineutrophil cytoplasmic antibody idiotype (5/7 Id) whose antiidiotype inhibits proteinase 3-antineutrophil cytoplasmic antibody antigen binding activity.
abstract: OBJECTIVE
  To evaluate the potential of a monoclonal proteinase 3-antineutrophil cytoplasmic antibody (PR3-ANCA) antiidiotype autoantibody (5/7 anti-Id) as a candidate for specific immunotherapy in Wegener's granulomatosis (WG), and to estimate the immunodiagnostic value of the corresponding idiotype (5/7 Id).
  
  
  METHODS
  We analyzed the incidence of 5/7 Id in patients with ANCA-associated vasculitides (WG, microscopic polyangiitis, Churg-Strauss syndrome), in disease controls (systemic lupus erythematosus patients), and in healthy donors. We then investigated the presence of 5/7 Id in relation to disease stage, clinical activity, and organ manifestations in 86 patients with WG. Finally, we investigated the ability of the 5/7 anti-Id reagent to inhibit the binding of PR3-ANCA to corresponding antigen in 19 WG patients.
  
  
  RESULTS
  The incidence of 5/7 Id was significantly more frequent in WG patients (43 of 86; 50%). We did not find a significant correlation between the prevalence of idiotype expression and disease activity or organ manifestations. Further, we demonstrated in vitro suppression of PR3-ANCA antigen binding activity by 5/7 anti-Id in 11 of 19 WG patients who were positive for 5/7 Id.
  
  
  CONCLUSIONS
  This study shows that 5/7 Id is a common idiotype with a significantly increased incidence in WG and that 5/7 anti-Id inhibits PR3-ANCA antigen binding activity. Based on these observations, we conclude that 5/7 anti-Id is a promising tool for the development of a specific immunotherapy for WG.
authors.affiliation: University of Lübeck, Germany.
authors.forename: H P
authors.initials: HP
authors.lastname: Strunz
authors.forename: E
authors.initials: E
authors.lastname: Csernok
authors.forename: W L
authors.initials: WL
authors.lastname: Gross
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000032:analysis / Q000276:immunology*; D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D015415:Biomarkers; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D014890:Granulomatosis with Polyangiitis / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011485:Protein Binding / Q000276:immunology; D012697:Serine Endopeptidases / Q000276:immunology*; D014657:Vasculitis / Q000175:diagnosis / Q000276:immunology*
chemical_list: D000888:Antibodies, Anti-Idiotypic; D019268:Antibodies, Antineutrophil Cytoplasmic; D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D015415:Biomarkers; D012697:Serine Endopeptidases