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

An Sofie Schelpe, Elien Roose, Bérangère S. Joly, Inge Pareyn, Ilaria Mancini, Marina Biganzoli, Hans Deckmyn, Jan Voorberg, Rob Fijnheer, Flora Peyvandi, Simon F. De Meyer, Paul Coppo, Agnès Veyradier, Karen Vanhoorelbeke

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)1268-1276
Number of pages9
JournalHaematologica
Volume104
Issue number6
DOIs
Publication statusPublished - Jan 1 2019

ASJC Scopus subject areas

  • Hematology

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    Schelpe, A. S., Roose, E., Joly, B. S., Pareyn, I., Mancini, I., Biganzoli, M., Deckmyn, H., Voorberg, J., Fijnheer, R., Peyvandi, F., De Meyer, S. F., Coppo, P., Veyradier, A., & Vanhoorelbeke, K. (2019). Generation of anti-idiotypic antibodies to detect anti-spacer antibody idiotopes in acute thrombotic thrombocytopenic purpura patients. Haematologica, 104(6), 1268-1276. https://doi.org/10.3324/haematol.2018.205666