Induction of aquaporin 4-reactive antibodies in Lewis rats immunized with aquaporin 4 mimotopes
| Autor: | Monika Bradl, Maria Isabel Leite, Markus Reindl, Felix Niederschick, Michael Szalay, Magdalini Nigritinou, Hans Lassmann, Kazuo Fujihara, Irina Tsymala, Fritz Leutmezer, Bleranda Zeka, Rouven Schulz, Tatsuro Misu, Florence Pache, Mia Matković, Kathrin Schanda, Jeffrey Bennett, Petra Scholze, Isabel J. Bauer, Zsolt Illes, Jacqueline Palace, Magdalena Lerch, Charlotte Dahle, Paulus S. Rommer |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
medicine.medical_specialty
Neurology Central nervous system Infections Autoantigens Epitope Antibodies lcsh:RC346-429 Pathology and Forensic Medicine Mimotopes Epitopes Cellular and Molecular Neuroscience medicine Lewis rats Animals Humans Animal model lcsh:Neurology. Diseases of the nervous system Autoantibodies Aquaporin 4 biology business.industry Research Neuromyelitis Optica Autoantibody Neurosciences Rats Disease Models Animal medicine.anatomical_structure Immunization Rats Inbred Lew Neuromyelitis optica spectrum disorders Immunoglobulin G Immunology biology.protein Neurology (clinical) sense organs Antibody business Neurovetenskaper |
| Zdroj: | Acta Neuropathologica Communications, Vol 8, Iss 1, Pp 1-17 (2020) Tsymala, I, Nigritinou, M, Zeka, B, Schulz, R, Niederschick, F, Matković, M, Bauer, I J, Szalay, M, Schanda, K, Lerch, M, Misu, T, Fujihara, K, Bennett, J L, Dahle, C, Pache, F, Rommer, P, Leutmezer, F, Illes, Z, Leite, M I, Palace, J, Scholze, P, Reindl, M, Lassmann, H & Bradl, M 2020, ' Induction of aquaporin 4-reactive antibodies in Lewis rats immunized with aquaporin 4 mimotopes ', Acta Neuropathologica Communications, vol. 8, 49 . https://doi.org/10.1186/s40478-020-00920-x Acta Neuropathologica Communications |
| Popis: | 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. Funding Agencies|Else Kroner-Fresenius-Stiftung [2013_A283]; Austrian Science FundAustrian Science Fund (FWF) [P28476-B30, P32699B]; Austrian Ministery of Science, Research and Economy (BIGWIG-MS); Ministry of Education, Culture, Sports, Science and Technology of JapanMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT) |
| Databáze: | OpenAIRE |
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