Induction of aquaporin 4-reactive antibodies in Lewis rats immunized with aquaporin 4 mimotopes

Most cases of neuromyelitis optica spectrum disorders (NMOSD) harbor pathogenic autoantibodies against the water channel aquaporin 4 (AQP4). Binding of these antibodies to AQP4 on astrocytes initiates damage to these cells, which culminates in the formation of large tissue destructive lesions in the...

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Published in:Acta neuropathologica communications 2020-04, Vol.8 (1), p.49-49, Article 49
Main Authors: Tsymala, Irina, Nigritinou, Magdalini, Zeka, Bleranda, Schulz, Rouven, Niederschick, Felix, Matković, Mia, Bauer, Isabel J, Szalay, Michael, Schanda, Kathrin, Lerch, Magdalena, Misu, Tatsuro, Fujihara, Kazuo, Bennett, Jeffrey L, Dahle, Charlotte, Pache, Florence, Rommer, Paulus, Leutmezer, Fritz, Illes, Zsolt, Leite, Maria Isabel, Palace, Jacqueline, Scholze, Petra, Reindl, Markus, Lassmann, Hans, Bradl, Monika
Format: Article
Language:English
Subjects:
Amino acids
Animal model
Animals
Antibodies
Antigenic determinants
Aquaporin 4
Aquaporin 4 - immunology
Aquaporins
Autoantibodies
Autoantibodies - immunology
Autoantigens - immunology
Autoimmunity
Brain research
Cloning
Deoxyribonucleic acid
Disease Models, Animal
DNA
EDTA
Epitopes - immunology
Fibroblasts
Humans
Humidity
Immunoglobulin G - immunology
Immunoglobulins
Infections
Lasers
Medical research
Mimotopes
Neuromyelitis Optica - immunology
Neuromyelitis optica spectrum disorders
Peptides
Proteins
Rats
Rats, Inbred Lew
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cited_by cdi_FETCH-LOGICAL-c632t-8376bbabe44f219289370f75a1280b3ad2402797328fb6bc38f7f522e47cd5343
cites cdi_FETCH-LOGICAL-c632t-8376bbabe44f219289370f75a1280b3ad2402797328fb6bc38f7f522e47cd5343
container_end_page 49
container_issue 1
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container_title Acta neuropathologica communications
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creator Tsymala, Irina
Nigritinou, Magdalini
Zeka, Bleranda
Schulz, Rouven
Niederschick, Felix
Matković, Mia
Bauer, Isabel J
Szalay, Michael
Schanda, Kathrin
Lerch, Magdalena
Misu, Tatsuro
Fujihara, Kazuo
Bennett, Jeffrey L
Dahle, Charlotte
Pache, Florence
Rommer, Paulus
Leutmezer, Fritz
Illes, Zsolt
Leite, Maria Isabel
Palace, Jacqueline
Scholze, Petra
Reindl, Markus
Lassmann, Hans
Bradl, Monika
description Most cases of neuromyelitis optica spectrum disorders (NMOSD) harbor pathogenic autoantibodies against the water channel aquaporin 4 (AQP4). Binding of these antibodies to AQP4 on astrocytes initiates damage to these cells, which culminates in the formation of large tissue destructive lesions in the central nervous system (CNS). Consequently, untreated patients may become permanently blind or paralyzed. Studies on the induction and breakage of tolerance to AQP4 could be of great benefit for NMOSD patients. So far, however, all attempts to create suitable animal models by active sensitization have failed. We addressed this challenge and identified peptides, which mimic the conformational AQP4 epitopes recognized by pathogenic antibodies of NMOSD patients. Here we show that these mimotopes can induce the production of AQP4-reactive antibodies in Lewis rats. Hence, our results provide a conceptual framework for the formation of such antibodies in NMOSD patients, and aid to improve immunization strategies for the creation of animal models suitable for tolerance studies in this devastating disease.
doi_str_mv 10.1186/s40478-020-00920-x
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2051-5960
language eng
recordid cdi_doaj_primary_oai_doaj_org_article_31f94705aa8441cd9a1d41acfcb1be81
source Publicly Available Content Database (Proquest) (PQ_SDU_P3); PubMed Central Free
subjects Amino acids
Animal model
Animals
Antibodies
Antigenic determinants
Aquaporin 4
Aquaporin 4 - immunology
Aquaporins
Autoantibodies
Autoantibodies - immunology
Autoantigens - immunology
Autoimmunity
Brain research
Cloning
Deoxyribonucleic acid
Disease Models, Animal
DNA
EDTA
Epitopes - immunology
Fibroblasts
Humans
Humidity
Immunoglobulin G - immunology
Immunoglobulins
Infections
Lasers
Medical research
Mimotopes
Neuromyelitis Optica - immunology
Neuromyelitis optica spectrum disorders
Peptides
Proteins
Rats
Rats, Inbred Lew
title Induction of aquaporin 4-reactive antibodies in Lewis rats immunized with aquaporin 4 mimotopes
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