Anti-MOG IgG in EAE models clinical aspects of pediatric MOGAD.

Introduction: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a severe, autoantibody-mediated neuroinflammatory syndrome that disproportionately impacts children. Detection of conformation-specific anti-MOG IgG1 in the serum is central to MOGAD diagnosis, yet the pathogenic role of these antibodies remains unclear. We sought to develop a clinically informed model of pediatric MOGAD to study the immunopathogenesis that recapitulates 1) early age of disease onset, 2) anti-MOG IgG1 in serum, and 3) widespread inflammation in the CNS. Methods: We employed two approaches to model MOGAD using anti-MOG IgG in mice: 1) treating young C57BL/6 mice with the murine-derived monoclonal MOG antibody 8-18C5, and 2) using young IgH Results: Both exogenous and endogenous anti-MOG IgG exacerbated EAE disease in young mice. Compared to wild-type littermates (+/+), young IgH Discussion: Introduction of anti-MOG IgG in EAE recapitulates key aspects of pediatric MOGAD and enables dissection of the mechanisms underlying anti-MOG antibody-mediated immunopathogenesis.