Abstract | BACKGROUND AND OBJECTIVES: METHODS: We induced active MOG35-55 EAE in C57Bl/6 mice followed by the application of a monoclonal MOG- IgG (8-18C5) 10 days postimmunization (dpi). Animals were treated with either a specific monoclonal antibody against FcRn (α-FcRn, 4470) or an isotype-matched control IgG on 7, 10, and 13 dpi. Neurologic disability was scored daily on a 10-point scale. Visual acuity was assessed by optomotor reflex. Histopathologic hallmarks of disease were assessed in the spinal cord, optic nerve, and retina. Immune cell infiltration was visualized by immunohistochemistry, demyelination by Luxol fast blue staining and complement deposition and number of retinal ganglion cells by immunofluorescence. RESULTS: In MOG- IgG-augmented MOG35-55 EAE, anti-FcRn treatment significantly attenuated neurologic disability over the course of disease (mean area under the curve and 95% confidence intervals (CIs): α-FcRn [n = 27], 46.02 [37.89-54.15]; isotype IgG [n = 24], 66.75 [59.54-73.96], 3 independent experiments), correlating with reduced amounts of demyelination and macrophage infiltration into the spinal cord. T- and B-cell infiltration and complement deposition remained unchanged. Compared with isotype, anti-FcRn treatment prevented reduction of visual acuity over the course of disease (median cycles/degree and interquartile range: α-FcRn [n = 16], 0.50 [0.48-0.55] to 0.50 [0.48-0.58]; isotype IgG [n = 17], 0.50 [0.49-0.54] to 0.45 [0.39-0.51]). DISCUSSION: We show preserved optomotor response and ameliorated course of disease after anti-FcRn treatment in an experimental model using a monoclonal MOG- IgG to mimic MOGAD. Selectively targeting FcRn might represent a promising therapeutic approach in MOGAD.
|
Authors | Jana Remlinger, Adrian Madarasz, Kirsten Guse, Robert Hoepner, Maud Bagnoud, Ivo Meli, Moritz Feil, Mathias Abegg, Christopher Linington, Anthony Shock, Babak Boroojerdi, Peter Kiessling, Bryan Smith, Volker Enzmann, Andrew Chan, Anke Salmen |
Journal | Neurology(R) neuroimmunology & neuroinflammation
(Neurol Neuroimmunol Neuroinflamm)
Vol. 9
Issue 2
(03 2022)
ISSN: 2332-7812 [Electronic] United States |
PMID | 35027475
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Copyright | Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. |
Chemical References |
- Antibodies, Monoclonal
- Histocompatibility Antigens Class I
- Myelin-Oligodendrocyte Glycoprotein
- Receptors, Fc
- Fc receptor, neonatal
|
Topics |
- Animals
- Antibodies, Monoclonal
(pharmacology)
- Encephalomyelitis, Autoimmune, Experimental
(complications, drug therapy, etiology, immunology)
- Female
- Histocompatibility Antigens Class I
(immunology)
- Mice
- Mice, Inbred C57BL
- Myelin-Oligodendrocyte Glycoprotein
(immunology)
- Receptors, Fc
(immunology)
- Vision Disorders
|