Generation of anti-idiotypic antibodies to detect anti-spacer antibody idiotopes in acute thrombotic thrombocytopenic purpura patients

Haematologica. 2019 Jun;104(6):1268-1276. doi: 10.3324/haematol.2018.205666. Epub 2018 Dec 6.


In autoantibody-mediated autoimmune diseases, autoantibody profiling allows patients to be stratified and links autoantibodies with disease severity and outcome. However, in immune-mediated thrombotic thrombocytopenic purpura (iTTP) patients, stratification according to antibody profiles and their clinical relevance has not been fully explored. We aimed to develop a new type of autoantibody profiling assay for iTTP based on the use of anti-idiotypic antibodies. Anti-idiotypic antibodies against 3 anti-spacer autoantibodies were generated in mice and were used to capture the respective anti-spacer idiotopes from 151 acute iTTP plasma samples. We next deciphered these anti-spacer idiotope profiles in iTTP patients and investigated whether these limited idiotope profiles could be linked with disease severity. We developed 3 anti-idiotypic antibodies that recognized particular idiotopes in the anti-spacer autoantibodies II-1, TTP73 or I-9, that are involved in ADAMTS13 binding; 35%, 24% and 42% of patients were positive for antibodies with the II-1, TTP73 and I-9 idiotopes, respectively. Stratifying patients according to the corresponding 8 anti-spacer idiotope profiles provided a new insight into the anti-spacer II-1, TTP73 and I-9 idiotope profiles in these patients. Finally, these limited idiotope profiles showed no association with disease severity. We successfully developed 3 anti-idiotypic antibodies that allowed us to determine the profiles of the anti-spacer II-1, TTP73 and I-9 idiotopes in iTTP patients. Increasing the number of patients and/or future development of additional anti-idiotypic antibodies against other anti-ADAMTS13 autoantibodies might allow idiotope profiles of clinical, prognostic value to be identified.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAMTS13 Protein / immunology
  • ADAMTS13 Protein / metabolism
  • Animals
  • Antibodies, Anti-Idiotypic / immunology*
  • Autoantibodies / immunology*
  • Autoantigens / metabolism
  • Disease Susceptibility / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Epitopes / immunology
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Protein Binding / immunology
  • Purpura, Thrombotic Thrombocytopenic / diagnosis
  • Purpura, Thrombotic Thrombocytopenic / immunology*
  • Purpura, Thrombotic Thrombocytopenic / metabolism
  • Severity of Illness Index


  • Antibodies, Anti-Idiotypic
  • Autoantibodies
  • Autoantigens
  • Epitopes
  • Immunoglobulin G
  • ADAMTS13 Protein
  • ADAMTS13 protein, human