title: Recombinant ADAMTS13 normalizes von Willebrand factor-cleaving activity in plasma of acquired TTP patients by overriding inhibitory antibodies.
abstract: BACKGROUND
  Severe deficiency of the von Willebrand factor (VWF)-cleaving protease ADAMTS13 as observed in acquired thrombotic thrombocytopenic purpura (TTP) is caused by inhibitory and non-inhibitory autoantibodies directed against the protease. Current treatment with plasma exchange is considered to remove circulating antibodies and to concurrently replenish the deficient enzyme.
  
  
  OBJECTIVE
  To explore the use of recombinant ADAMTS13 (rADAMTS13) as a potential therapeutic agent in acquired TTP, we investigated its efficacy in normalizing VWF-cleaving activity in the presence of ADAMTS13 inhibitors.
  
  
  METHODS
  Thirty-six plasma samples from TTP patients were adjusted to predefined inhibitor titers, and recovery of ADAMTS13 activity was analyzed following supplementation with rADAMTS13.
  
  
  RESULTS
  We showed a linear relation between the inhibitor titer measured and effective rADAMTS13 concentration necessary for reconstitution of VWF-cleaving activity in the presence of neutralizing autoantibodies.
  
  
  CONCLUSIONS
  Our results support the further investigation of the potential therapeutic applicability of rADAMTS13 as an adjunctive therapy in acquired TTP.
authors.affiliation: Baxter Innovations GmbH, Wagramer Strasse, Vienna, Austria.
authors.forename: B
authors.initials: B
authors.lastname: Plaimauer
authors.forename: J A
authors.initials: JA
authors.lastname: Kremer Hovinga
authors.forename: C
authors.initials: C
authors.lastname: Juno
authors.forename: M J
authors.initials: MJ
authors.lastname: Wolfsegger
authors.forename: S
authors.initials: S
authors.lastname: Skalicky
authors.forename: M
authors.initials: M
authors.lastname: Schmidt
authors.forename: L
authors.initials: L
authors.lastname: Grillberger
authors.forename: M
authors.initials: M
authors.lastname: Hasslacher
authors.forename: P
authors.initials: P
authors.lastname: Knöbl
authors.forename: H
authors.initials: H
authors.lastname: Ehrlich
authors.forename: F
authors.initials: F
authors.lastname: Scheiflinger
mesh_terms: D051722:ADAM Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000071120:ADAMTS13 Protein; D000328:Adult; D000368:Aged; D000906:Antibodies / Q000737:chemistry*; D000941:Antigens / Q000737:chemistry; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010951:Plasma Exchange; D011697:Purpura, Thrombotic Thrombocytopenic / Q000097:blood* / Q000276:immunology / Q000628:therapy*; D011994:Recombinant Proteins / Q000378:metabolism; D014841:von Willebrand Factor / Q000378:metabolism*
chemical_list: D000906:Antibodies; D000941:Antigens; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human