Binding patterns and functional properties of human antibodies to AQP4 and MOG on murine optic nerve and retina

Simon Faissner; Florian Graz; Sabrina Reinehr; Laura Petrikowski; Steffen Haupeltshofer; Ulaş Ceylan; Gesa Stute; Stephan Winklmeier; Florence Pache; Friedemann Paul; Klemens Ruprecht; Edgar Meinl; H Burkhard Dick; Ralf Gold; Ingo Kleiter; Stephanie C Joachim

doi:10.1016/j.jneuroim.2020.577194

Binding patterns and functional properties of human antibodies to AQP4 and MOG on murine optic nerve and retina

J Neuroimmunol. 2020 Feb 20:342:577194. doi: 10.1016/j.jneuroim.2020.577194. Online ahead of print.

Authors

Simon Faissner¹, Florian Graz², Sabrina Reinehr³, Laura Petrikowski², Steffen Haupeltshofer⁴, Ulaş Ceylan⁴, Gesa Stute³, Stephan Winklmeier⁵, Florence Pache⁶, Friedemann Paul⁷, Klemens Ruprecht⁶, Edgar Meinl⁵, H Burkhard Dick³, Ralf Gold⁴, Ingo Kleiter⁸, Stephanie C Joachim⁹

Affiliations

¹ Department of Neurology, Ruhr-University Bochum, St. Josef-Hospital, Gudrunstr. 56, 44791 Bochum, Germany. Electronic address: [email protected].
² Department of Neurology, Ruhr-University Bochum, St. Josef-Hospital, Gudrunstr. 56, 44791 Bochum, Germany; Experimental Eye Research Institute, University Eye Hospital, Ruhr-University Bochum, In der Schornau 23-25, 44892 Bochum, Germany.
³ Experimental Eye Research Institute, University Eye Hospital, Ruhr-University Bochum, In der Schornau 23-25, 44892 Bochum, Germany.
⁴ Department of Neurology, Ruhr-University Bochum, St. Josef-Hospital, Gudrunstr. 56, 44791 Bochum, Germany.
⁵ Institute of Clinical Neuroimmunology, Ludwig-Maximilians-Universität München, Munich, Germany.
⁶ Department of Neurology, Charité - Universitaetsmedizin Berlin, Berlin, Germany.
⁷ Department of Neurology, Charité - Universitaetsmedizin Berlin, Berlin, Germany; NeuroCure Clinical Research Center und Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité - Universitaetsmedizin Berlin, Berlin, Germany.
⁸ Department of Neurology, Ruhr-University Bochum, St. Josef-Hospital, Gudrunstr. 56, 44791 Bochum, Germany; Marianne-Strauß-Klinik, Behandlungszentrum Kempfenhausen für Multiple Sklerose Kranke, Berg, Germany.
⁹ Experimental Eye Research Institute, University Eye Hospital, Ruhr-University Bochum, In der Schornau 23-25, 44892 Bochum, Germany; Department of Neurology, Ruhr-University Bochum, St. Josef-Hospital, Gudrunstr. 56, 44791 Bochum, Germany. Electronic address: [email protected].

PMID: 32143071
DOI: 10.1016/j.jneuroim.2020.577194

Abstract

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune-inflammatory CNS disease affecting spinal cord and optic nerves, mediated by autoantibodies against aquaporin-4 (AQP4) and myelin-oligodendrocyte-glycoprotein (MOG). Effects of those immunoglobulins (Ig) on retina and optic nerve are incompletely understood. We investigated AQP4-IgG and MOG-IgG sera on retina and optic nerve ex vivo and in 2D2 mice, which harbor a transgenic MOG-specific T-cell receptor. Some sera reacted with murine retina and optic nerve showing distinct binding patterns, suggesting different epitopes being targeted in both subgroups. Transfer of total IgG from a MOG-IgG positive patient to 2D2 mice did neither enhance disability nor induce functional or histological alterations in the retina.

Keywords: Aquaporin-4; Autoimmunity; Myelin-oligodendrocyte-glycoprotein; Neuromyelitis optica spectrum disorder; Optic nerve; Retina.