Generation of anti-idiotypic antibodies to detect anti-spacer antibody idiotopes in acute thrombotic thrombocytopenic purpura patients.
ADAMTS13 Protein
/ immunology
Animals
Antibodies, Anti-Idiotypic
/ immunology
Autoantibodies
/ immunology
Autoantigens
/ metabolism
Disease Susceptibility
/ immunology
Enzyme-Linked Immunosorbent Assay
Epitopes
/ immunology
Humans
Immunoglobulin G
/ blood
Protein Binding
/ immunology
Purpura, Thrombotic Thrombocytopenic
/ diagnosis
Severity of Illness Index
Journal
Haematologica
ISSN: 1592-8721
Titre abrégé: Haematologica
Pays: Italy
ID NLM: 0417435
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
06
09
2018
accepted:
30
11
2018
pubmed:
14
12
2018
medline:
19
5
2020
entrez:
8
12
2018
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 30523052
pii: haematol.2018.205666
doi: 10.3324/haematol.2018.205666
pmc: PMC6545854
doi:
Substances chimiques
Antibodies, Anti-Idiotypic
0
Autoantibodies
0
Autoantigens
0
Epitopes
0
Immunoglobulin G
0
ADAMTS13 Protein
EC 3.4.24.87
ADAMTS13 protein, human
EC 3.4.24.87
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1268-1276Informations de copyright
Copyright© 2019 Ferrata Storti Foundation.
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