Abstract Details

Title Anti-MOG IgG in EAE Models Clinical Aspects of Pediatric MOGAD

Topic Autoimmune Neurology

Presentation(s) P6 - Poster Session 6 (5:00 PM-6:00 PM)

Poster/Presentation
Number 1-010

Objective

The objective of this study was to establish a pediatric MOGAD model that reproduces key clinical features and enables investigation of anti-MOG IgG-mediated immunopathogenesis.

Background Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a severe, autoantibody-mediated demyelinating syndrome that disproportionally 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 immunopathogenesis that recapitulated (1) early age of disease onset, (2) anti-MOG IgG1 in the serum, and (3) diffuse inflammatory demyelination in the CNS.

Design/Methods We employed two complementary approaches to model anti-MOG IgG1: (1) passive transfer of the murine-derived monoclonal antibody 8-18C5 into young C57BL/6 mice and (2) young transgenic IgH^MOG mice expressing the same clonotype endogenously. Experimental autoimmune encephalomyelitis (EAE) was induced by immunization with MOG_35-55to elicit inflammatory demyelination. Immunophenotyping and neuroinflammation were characterized by flow cytometry, confocal microscopy, magnetic resonance imaging (MRI), and in vitro phagocytosis assays.

Results Following MOG_35-55 immunization, both exogenous and endogenous anti-MOG IgG1 exacerbated EAE disease in young mice. Young IgH^MOG mice exhibited reduced peripheral immune cell counts and increased CNS immune infiltration compared to wild-type littermates. IgH^MOGmice developed circumferential longitudinal myelitis, bilateral optic neuritis, and multifocal brain inflammation. CNS innate immune cells, including microglia, showed downregulation of surface CD16/CD32, which corresponded with enhanced microglial phagocytosis of MOG in vitro.

Conclusions Anti-MOG IgG in EAE recapitulates key aspects of pediatric MOGAD and enables dissection of the mechanisms underlying antibody-mediated immunopathogenesis. Using these models, we identified antibody-mediated microglial phagocytosis of MOG as a novel activity of anti-MOG IgG.

Authors/Disclosures
Yike Jiang PRESENTER	Yike Jiang has nothing to disclose.
Estefany Y. Reyes, PhD	Dr. Reyes has nothing to disclose.
Elliot Yi-Hsin Lin, MS	Mr. Lin has nothing to disclose.
Emily Troutman, Graduate Student	Ms. Troutman has nothing to disclose.
Miranda Lumbreras	Mrs. Lumbreras has nothing to disclose.
Devon DiPalma	Mr. DiPalma has nothing to disclose.
Heather Van Mater, MD	Dr. Van Mater has nothing to disclose.
Mari Shinohara, PhD	The institution of Prof. Shinohara has received research support from Ono Pharmaceuticals.

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