Generation of anti-idiotypic antibodies to detect anti-spacer antibody idiotopes in acute thrombotic thrombocytopenic purpura patients
| Autor: | Inge Pareyn, Rob Fijnheer, Jan Voorberg, Karen Vanhoorelbeke, Simon F. De Meyer, Marina Biganzoli, Bérangère S. Joly, Flora Peyvandi, Hans Deckmyn, An Sofie Schelpe, Elien Roose, Agnès Veyradier, Ilaria Mancini, Paul Coppo |
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| Přispěvatelé: | Experimental Vascular Medicine, Landsteiner Laboratory, ACS - Microcirculation |
| Rok vydání: | 2018 |
| Předmět: |
Thrombotic thrombocytopenic purpura
ADAMTS13 Protein Enzyme-Linked Immunosorbent Assay Autoantigens Severity of Illness Index MICROANGIOPATHY VALIDATION Article Epitopes 03 medical and health sciences 0302 clinical medicine BINDING Severity of illness Animals Humans Medicine Clinical significance Autoantibodies Hemostasis Science & Technology Purpura Thrombotic Thrombocytopenic biology ANTI-ADAMTS13 ANTIBODIES business.industry Autoantibody Idiotopes Hematology medicine.disease CAPLACIZUMAB ADAMTS13 ADAMTS13 ACTIVITY Antibodies Anti-Idiotypic 3. Good health PROGNOSTIC VALUE UREMIC SYNDROME Immunoglobulin G Immunology Anti-idiotypic antibodies biology.protein AUTOANTIBODIES Disease Susceptibility Antibody business Life Sciences & Biomedicine MAIN IMMUNOGENIC REGION Protein Binding 030215 immunology |
| Zdroj: | Haematologica Haematologica, 104(6), 1268-1276. Ferrata Storti Foundation |
| ISSN: | 1592-8721 0390-6078 |
| DOI: | 10.3324/haematol.2018.205666 |
| Popis: | 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. ispartof: HAEMATOLOGICA vol:104 issue:6 pages:1268-1276 ispartof: location:Italy status: published |
| Databáze: | OpenAIRE |
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