title: Evidence for a role of anti-ADAMTS13 autoantibodies despite normal ADAMTS13 activity in recurrent thrombotic thrombocytopenic purpura.
abstract: BACKGROUND
  Severe ADAMTS13 deficiency is a critical component of the pathogenesis of idiopathic thrombotic thrombocytopenic purpura but is found only in about 60% of patients clinically diagnosed with this disease.
  
  
  METHODS
  Over a period of 8 years and six episodes of thrombotic thrombocytopenic purpura we studied the evolution of the anti-ADAMTS13 antibody response in a patient using different ADAMTS13 assays and epitope mapping.
  
  
  RESULTS
  Anti-ADAMTS13 autoantibodies were found in all episodes but were inhibitory only in the last two episodes. In a flow-based assay, normal ADAMTS13 activity was found only during the first disease episode, while ADAMTS13 activity was normal using a static assay in episodes 1 and 3, and severely deficient in the last two episodes. Fluorescence evolution in a modified fluorescence resonance energy transfer assay using a von Willebrand factor A2 domain peptide substrate was linear in episodes 1, 5 and 6, but increased exponentially in episodes 3 and 4. Despite the variable functional characteristics of the anti-ADAMTS13 autoantibodies, their principal epitope was the ADAMTS13 spacer domain in all episodes.
  
  
  CONCLUSIONS
  The patient is unique as he displayed features of maturation or shaping of the anti-ADAMTS13 autoantibody response during the course of multiple episodes of thrombotic thrombocytopenic purpura. Anti-ADAMTS13 autoantibodies may be important in vivo despite normal ADAMTS13 activity in routine assays. Consequently, treatment decisions should not be based solely on activity assay results.
authors: University Clinic of Hematology and Central Hematology Laboratory, Inselspital, University Hospital and the University of Bern, Bern, Switzerland.
authors: Rahel
authors: R
authors: Froehlich-Zahnd
authors: James N
authors: JN
authors: George
authors: Sara K
authors: SK
authors: Vesely
authors: Deirdra R
authors: DR
authors: Terrell
authors: Khatira
authors: K
authors: Aboulfatova
authors: Jing-Fei
authors: JF
authors: Dong
authors: Brenda M
authors: BM
authors: Luken
authors: Jan
authors: J
authors: Voorberg
authors: Ulrich
authors: U
authors: Budde
authors: Irmela
authors: I
authors: Sulzer
authors: Bernhard
authors: B
authors: Lämmle
authors: Johanna A
authors: JA
authors: Kremer Hovinga
mesh_terms: D051722:ADAM Proteins / Q000097:blood* / Q000378:metabolism; D000071120:ADAMTS13 Protein; D000328:Adult; D001323:Autoantibodies / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D008297:Male; D011697:Purpura, Thrombotic Thrombocytopenic / Q000097:blood* / Q000201:enzymology*; D012008:Recurrence
chemical_list: D001323:Autoantibodies; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human