Induction of aquaporin 4-reactive antibodies in Lewis rats immunized with aquaporin 4 mimotopes
Abstract 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 lesio...
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doaj-31f94705aa8441cd9a1d41acfcb1be812020-11-25T02:07:51ZengBMCActa Neuropathologica Communications2051-59602020-04-018111710.1186/s40478-020-00920-xInduction of aquaporin 4-reactive antibodies in Lewis rats immunized with aquaporin 4 mimotopesIrina Tsymala0Magdalini Nigritinou1Bleranda Zeka2Rouven Schulz3Felix Niederschick4Mia Matković5Isabel J. Bauer6Michael Szalay7Kathrin Schanda8Magdalena Lerch9Tatsuro Misu10Kazuo Fujihara11Jeffrey L. Bennett12Charlotte Dahle13Florence Pache14Paulus Rommer15Fritz Leutmezer16Zsolt Illes17Maria Isabel Leite18Jacqueline Palace19Petra Scholze20Markus Reindl21Hans Lassmann22Monika Bradl23Department Neuroimmunology, Medical University Vienna, Center for Brain ResearchDepartment Neuroimmunology, Medical University Vienna, Center for Brain ResearchDepartment Neuroimmunology, Medical University Vienna, Center for Brain ResearchDepartment Neuroimmunology, Medical University Vienna, Center for Brain ResearchDepartment Neuroimmunology, Medical University Vienna, Center for Brain ResearchDepartment Neuroimmunology, Medical University Vienna, Center for Brain ResearchDepartment Neuroimmunology, Medical University Vienna, Center for Brain ResearchDepartment Pathobiology of the Nervous System, Medical University Vienna, Center for Brain ResearchClinical Department of Neurology, Medical University of InnsbruckClinical Department of Neurology, Medical University of InnsbruckDepartments of Multiple Sclerosis Therapeutics and Neurology, Tohoku University Graduate School of MedicineDepartments of Multiple Sclerosis Therapeutics and Neurology, Tohoku University Graduate School of MedicineDepartment of Neurology, Neuroscience Program, University of ColoradoDepartment of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping UniversityDepartment of Neurology and NeuroCure Clinical Research Center, Charité-Universitätsmedizin BerlinDepartment of Neurology, Medical University ViennaDepartment of Neurology, Medical University ViennaDepartment of Neurology, Odense University Hospital and University of Southern DenmarkNuffield Department of Clinical Neurosciences, John Radcliffe HospitalNuffield Department of Clinical Neurosciences, John Radcliffe HospitalDepartment Pathobiology of the Nervous System, Medical University Vienna, Center for Brain ResearchClinical Department of Neurology, Medical University of InnsbruckDepartment Neuroimmunology, Medical University Vienna, Center for Brain ResearchDepartment Neuroimmunology, Medical University Vienna, Center for Brain ResearchAbstract 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.http://link.springer.com/article/10.1186/s40478-020-00920-xNeuromyelitis optica spectrum disordersAntibodiesMimotopesAquaporin 4InfectionsAnimal model |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Irina Tsymala Magdalini Nigritinou Bleranda Zeka Rouven Schulz Felix Niederschick Mia Matković Isabel J. Bauer Michael Szalay Kathrin Schanda Magdalena Lerch Tatsuro Misu Kazuo Fujihara Jeffrey L. Bennett Charlotte Dahle Florence Pache Paulus Rommer Fritz Leutmezer Zsolt Illes Maria Isabel Leite Jacqueline Palace Petra Scholze Markus Reindl Hans Lassmann Monika Bradl |
spellingShingle |
Irina Tsymala Magdalini Nigritinou Bleranda Zeka Rouven Schulz Felix Niederschick Mia Matković Isabel J. Bauer Michael Szalay Kathrin Schanda Magdalena Lerch Tatsuro Misu Kazuo Fujihara Jeffrey L. Bennett Charlotte Dahle Florence Pache Paulus Rommer Fritz Leutmezer Zsolt Illes Maria Isabel Leite Jacqueline Palace Petra Scholze Markus Reindl Hans Lassmann Monika Bradl Induction of aquaporin 4-reactive antibodies in Lewis rats immunized with aquaporin 4 mimotopes Acta Neuropathologica Communications Neuromyelitis optica spectrum disorders Antibodies Mimotopes Aquaporin 4 Infections Animal model |
author_facet |
Irina Tsymala Magdalini Nigritinou Bleranda Zeka Rouven Schulz Felix Niederschick Mia Matković Isabel J. Bauer Michael Szalay Kathrin Schanda Magdalena Lerch Tatsuro Misu Kazuo Fujihara Jeffrey L. Bennett Charlotte Dahle Florence Pache Paulus Rommer Fritz Leutmezer Zsolt Illes Maria Isabel Leite Jacqueline Palace Petra Scholze Markus Reindl Hans Lassmann Monika Bradl |
author_sort |
Irina Tsymala |
title |
Induction of aquaporin 4-reactive antibodies in Lewis rats immunized with aquaporin 4 mimotopes |
title_short |
Induction of aquaporin 4-reactive antibodies in Lewis rats immunized with aquaporin 4 mimotopes |
title_full |
Induction of aquaporin 4-reactive antibodies in Lewis rats immunized with aquaporin 4 mimotopes |
title_fullStr |
Induction of aquaporin 4-reactive antibodies in Lewis rats immunized with aquaporin 4 mimotopes |
title_full_unstemmed |
Induction of aquaporin 4-reactive antibodies in Lewis rats immunized with aquaporin 4 mimotopes |
title_sort |
induction of aquaporin 4-reactive antibodies in lewis rats immunized with aquaporin 4 mimotopes |
publisher |
BMC |
series |
Acta Neuropathologica Communications |
issn |
2051-5960 |
publishDate |
2020-04-01 |
description |
Abstract 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. |
topic |
Neuromyelitis optica spectrum disorders Antibodies Mimotopes Aquaporin 4 Infections Animal model |
url |
http://link.springer.com/article/10.1186/s40478-020-00920-x |
work_keys_str_mv |
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