title: VH1-69 germline encoded antibodies directed towards ADAMTS13 in patients with acquired thrombotic thrombocytopenic purpura.
abstract: BACKGROUND
  Autoantibodies directed towards ADAMTS13 are present in the majority of patients with acquired thrombotic thrombocytopenic purpura (TTP). Analysis of a set of antibodies derived from two patients with acquired TTP revealed frequent use of the VH1-69 heavy chain gene segment for the assembly of anti-ADAMTS13 antibodies.
  
  
  OBJECTIVE
  We explored the ability of two VH1-69 germline gene-encoded antibodies to inhibit the von Willebrand factor (VWF)-processing activity of ADAMTS13 under different experimental conditions. Furthermore, the presence of VH1-69 encoded anti-ADAMTS13 antibodies in 40 patients with acquired TTP was monitored using monoclonal antibody G8, which specifically reacts with an idiotype expressed on VH1-69 encoded antibodies.
  
  
  RESULTS
  Binding of the two VH1-69 encoded monoclonal antibodies was dependent on the presence of the spacer domain. Both antibodies inhibited ADAMTS13 activity under static conditions, as measured by cleavage of FRETS-VWF73 substrate and cleavage of VWF multimers. The recombinant antibodies were also capable of inhibiting the processing of UL-VWF strings on the surface of endothelial cells. G8-reactive antibodies directed towards ADAMTS13 were present in plasma of all patients containing anti ADAMTS13 antibodies.
  
  
  CONCLUSIONS
  These results suggest that VH1-69 derived antibodies directed towards ADAMTS13 develop in the majority of patients with acquired TTP.
authors.affiliation: Department of Plasma Proteins, Sanquin-AMC Landsteiner Laboratory, Amsterdam, The Netherlands.
authors.forename: W
authors.initials: W
authors.lastname: Pos
authors.forename: B M
authors.initials: BM
authors.lastname: Luken
authors.forename: J A
authors.initials: JA
authors.lastname: Kremer Hovinga
authors.forename: E A M
authors.initials: EA
authors.lastname: Turenhout
authors.forename: F
authors.initials: F
authors.lastname: Scheiflinger
authors.forename: J-F
authors.initials: JF
authors.lastname: Dong
authors.forename: R
authors.initials: R
authors.lastname: Fijnheer
authors.forename: J
authors.initials: J
authors.lastname: Voorberg
mesh_terms: D051722:ADAM Proteins / Q000276:immunology*; D000071120:ADAMTS13 Protein; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001323:Autoantibodies / Q000276:immunology*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D011697:Purpura, Thrombotic Thrombocytopenic / Q000276:immunology*; D014841:von Willebrand Factor / Q000187:drug effects
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D007143:Immunoglobulin Heavy Chains; D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human