2024 American Academy of Neurology Abstract Website

Marianna Spatola¹, Omar Chuquisana², Wonyeong Jung¹, Joseph Lopez³, Eva Maria Wendel⁴, Sudarshini Ramanathan⁵, Christian Keller², Tim Hahn⁶, Edgar Meinl⁷, Markus Reindl⁸, Russell Dale³, Heinz Wiendl², Douglas Lauffenburger⁹, Kevin Rostasy¹⁰, Fabienne Brilot¹¹, Galit Alter¹, Jan Lunemann²
¹Ragon Institute of MGH, MIT and Harvard Medical School, ²Department of Neurology with Institute of Translational Neurology, University Hospital Münster, ³Brain Autoimmunity Group, Kids Neuroscience Centre, Kids Research at the Children's Hospital at Westmead, ⁴Department of Pediatric Neurology, Olgahospital/Klinikum Stuttgart, ⁵Department of Neurology, Concord Hospital, ⁶Institute for Translational Psychiatry, University of Münster, ⁷Institute of Clinical Neuroimmunology, Biomedical Center and University Hospital, Ludwig-Maximilians-Universität, ⁸Clinical Department of Neurology, Medical University of Innsbruck, ⁹Massachusetts Institute of Technology, ¹⁰Department of Pediatric Neurology, Children's Hospital Datteln, University Witten/Herdecke, ¹¹Brain and Mind Centre, The University of Sydney

Objective:

To systematically profile the biochemical and functional landscape of human Myelin oligodendrocyte glycoprotein (MOG)-antibodies (Abs) in pediatric and adult patients diagnosed with MOG-Ab-associated disease (MOGAD) using an unbiased, high-throughput systems serology platform and to identify humoral correlates for human MOG-Ab associated clinical disease features.

Background:

MOGAD is an inflammatory demyelinating disease of the central nervous system. Although MOG is encephalitogenic in different mammalian species, the mechanisms by which human MOG-specific Abs contribute to MOGAD are poorly understood.

Design/Methods:

A systems-level approach combined with high-dimensional characterization of Ab-associated immune features was employed to deeply profile humoral immune responses in 123 patients with MOGAD.

Results:

We show that age is a major determinant for MOG-antibody related immune signatures. Unsupervised clustering additionally identifies two dominant immunological endophenotypes of MOGAD. The pro-inflammatory endophenotype characterized by increased binding affinities for activating Fcγ receptors (FcγR), capacity to activate innate immune cells, and decreased frequencies of galactosylated and sialylated IgG glycovariants is associated with clinically active disease.

Conclusions:

Our data support the concept that FcγR-mediated effector functions control the pathogenicity of MOG-specific IgG and suggests that FcγR-targeting therapies should be explored for their therapeutic potential in MOGAD.