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Haematologica. 2018 Dec 6. pii: haematol.2018.205666. doi: 10.3324/haematol.2018.205666. [Epub ahead of print]

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

Author information

1
Laboratory for Thrombosis Research, IRF Life Sciences, KU Leuven Campus Kulak Kortrijk.
2
Service Hematologie Biologique, Hopital Lariboisiere, Assistance Publique-Hopitaux de Paris.
3
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico.
4
Department of Molecular and Cellular Hemostasis, Sanquin-AMC Landsteiner Laboratory.
5
Department of Internal Medicine, Meander Medical Center.
6
Sorbonne Universités, Paris, Paris, France.
7
Laboratory for Thrombosis Research, IRF Life Sciences, KU Leuven Campus Kulak Kortrijk; karen.vanhoorelbeke@kuleuven.be.

Abstract

In autoantibody-mediated autoimmune diseases, autoantibody profiling allows to stratify patients and link autoantibodies with disease severity and outcome. However, in immune-mediated thrombotic thrombocytopenic purpura patients, stratification according to antibody profiles and their clinical relevance has not been fully explored. We aimed at developing a new type of autoantibody profiling assay for immune-mediated thrombotic thrombocytopenic purpura 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 immune-mediated thrombotic thrombocytopenic purpura plasma samples. We next deciphered these anti-spacer idiotope profiles in immune-mediated thrombotic thrombocytopenic purpura patients and investigated if 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. Thirty-five, 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 revealed an until now unknown 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 immune-mediated thrombotic thrombocytopenic purpura patients. Increasing the number of patients and/or future development of additional anti-idiotypic antibodies against other anti-ADAMTS13 autoantibodies might allow to identify idiotope profiles of clinical, prognostic value.

KEYWORDS:

ADAMTS13; anti-idiotypic antibodies; antibody profiling; autoimmunity; thrombotic thrombocytopenic purpura

PMID:
30523052
DOI:
10.3324/haematol.2018.205666
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