Human antibodies against the myelin oligodendrocyte glycoprotein can cause complement-dependent demyelination
| العنوان: | Human antibodies against the myelin oligodendrocyte glycoprotein can cause complement-dependent demyelination |
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| المؤلفون: | Peschl, Patrick, Schanda, Kathrin, Zeka, Bleranda, Given, Katherine, Böhm, Denise, Ruprecht, Klemens, Saiz, Albert, Lutterotti, Andreas, Rostásy, Kevin, Höftberger, Romana, Berger, Thomas, Macklin, Wendy, Lassmann, Hans, Bradl, Monika, Bennett, Jeffrey L, Reindl, Markus |
| المساهمون: | University of Zurich, Reindl, Markus |
| المصدر: | Journal of Neuroinflammation Journal of Neuroinflammation, Vol 14, Iss 1, Pp 1-14 (2017) |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Adult, Male, Adolescent, 2804 Cellular and Molecular Neuroscience, 610 Medicine & health, Mice, Transgenic, lcsh:RC346-429, Antibodies, Mice, Young Adult, Organ Culture Techniques, immune system diseases, Cerebellum, Animals, Humans, MOG, Child, lcsh:Neurology. Diseases of the nervous system, Aged, Organotypic slice culture, 2403 Immunology, EAE, Research, Neuromyelitis Optica, 2800 General Neuroscience, Infant, hemic and immune systems, Complement System Proteins, Middle Aged, 10040 Clinic for Neurology, nervous system diseases, Rats, HEK293 Cells, nervous system, Myelin oligodendrocyte glycoprotein, Rats, Inbred Lew, 2808 Neurology, Child, Preschool, Neuromyelitis optica spectrum disorders, Female, Myelin-Oligodendrocyte Glycoprotein, Demyelinating Diseases |
| الوصف: | Background Antibodies to the myelin oligodendrocyte glycoprotein (MOG) are associated with a subset of inflammatory demyelinating diseases of the central nervous system such as acute disseminated encephalomyelitis and neuromyelitis optica spectrum disorders. However, whether human MOG antibodies are pathogenic or an epiphenomenon is still not completely clear. Although MOG is highly conserved within mammals, previous findings showed that not all human MOG antibodies bind to rodent MOG. We therefore hypothesized that human MOG antibody-mediated pathology in animal models may only be evident using species-specific MOG antibodies. Methods We screened 80 human MOG antibody-positive samples for their reactivity to mouse and rat MOG using either a live cell-based assay or immunohistochemistry on murine, rat, and human brain tissue. Selected samples reactive to either human MOG or rodent MOG were subsequently tested for their ability to induce complement-mediated damage in murine organotypic brain slices or enhance demyelination in an experimental autoimmune encephalitis (EAE) model in Lewis rats. The MOG monoclonal antibody 8-18-C5 was used as a positive control. Results Overall, we found that only a subset of human MOG antibodies are reactive to mouse (48/80, 60%) or rat (14/80, 18%) MOG. Purified serum antibodies from 10 human MOG antibody-positive patients (8/10 reactive to mouse MOG, 6/10 reactive to rat MOG), 3 human MOG-negative patients, and 3 healthy controls were tested on murine organotypic brain slices. Purified IgG from one patient with high titers of anti-human, mouse, and rat MOG antibodies and robust binding to myelin tissue produced significant, complement-mediated myelin loss in organotypic brain slices, but not in the EAE model. Monoclonal 8-18-C5 MOG antibody caused complement-mediated demyelination in both the organotypic brain slice model and in EAE. Conclusion This study shows that a subset of human MOG antibodies can induce complement-dependent pathogenic effects in a murine ex vivo animal model. Moreover, a high titer of species-specific MOG antibodies may be critical for demyelinating effects in mouse and rat animal models. Therefore, both the reactivity and titer of human MOG antibodies must be considered for future pathogenicity studies. Electronic supplementary material The online version of this article (10.1186/s12974-017-0984-5) contains supplementary material, which is available to authorized users. |
| وصف الملف: | s12974-017-0984-5.pdf - application/pdf |
| تدمد: | 1742-2094 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=pmid_dedup__::77b95a5242cfcf5604a02bc9c0f9b616Test https://pubmed.ncbi.nlm.nih.gov/29070051Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.pmid.dedup....77b95a5242cfcf5604a02bc9c0f9b616 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17422094 |
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