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Distinction and temporal stability of conformational epitopes on myelin oligodendrocyte glycoprotein recognized by patients with different inflammatory central nervous system diseases

Mayer, Marie C. and Breithaupt, Constanze and Reindl, Markus and Schanda, Kathrin and Rostásy, Kevin and Berger, Thomas and Dale, Russell C. and Brilot, Fabienne and Olsson, Tomas and Jenne, Dieter and Pröbstel, Anne-Katrin and Dornmair, Klaus and Wekerle, Hartmut and Hohlfeld, Reinhard and Banwell, Brenda and Bar-Or, Amit and Meinl, Edgar. (2013) Distinction and temporal stability of conformational epitopes on myelin oligodendrocyte glycoprotein recognized by patients with different inflammatory central nervous system diseases. Journal of immunology (Baltimore, Md. : 1950), 191 (7). pp. 3594-3604.

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Official URL: http://edoc.unibas.ch/51354/

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Abstract

Autoantibodies targeting conformationally intact myelin oligodendrocyte glycoprotein (MOG) are found in different inflammatory diseases of the CNS, but their antigenic epitopes have not been mapped. We expressed mutants of MOG on human HeLa cells and analyzed sera from 111 patients (104 children, 7 adults) who recognized cell-bound human MOG, but had different diseases, including acute disseminated encephalomyelitis (ADEM), one episode of transverse myelitis or optic neuritis, multiple sclerosis (MS), anti-aquaporin-4 (AQP4)-negative neuromyelitis optica (NMO), and chronic relapsing inflammatory optic neuritis (CRION). We obtained insight into the recognition of epitopes in 98 patients. All epitopes identified were located at loops connecting the β strands of MOG. The most frequently recognized MOG epitope was revealed by the P42S mutation positioned in the CC'-loop. Overall, we distinguished seven epitope patterns, including the one mainly recognized by mouse mAbs. In half of the patients, the anti-MOG response was directed to a single epitope. The epitope specificity was not linked to certain disease entities. Longitudinal analysis of 11 patients for up to 5 y indicated constant epitope recognition without evidence for intramolecular epitope spreading. Patients who rapidly lost their anti-MOG IgG still generated a long-lasting IgG response to vaccines, indicating that their loss of anti-MOG reactivity did not reflect a general lack of capacity for long-standing IgG responses. The majority of human anti-MOG Abs did not recognize rodent MOG, which has implications for animal studies. Our findings might assist in future detection of potential mimotopes and pave the way to Ag-specific depletion.
Faculties and Departments:03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Neurologie > Neuroimmunologie (Kappos)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Neurologie > Neuroimmunologie (Kappos)
UniBasel Contributors:Pröbstel, Anne-Katrin
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:The American Association of Immunologists, Inc.
ISSN:1550-6606
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:03 Oct 2017 08:27
Deposited On:03 Oct 2017 08:27

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