W126 - Proteogenomic Immune Signatures Delineate the Landscape of Pediatric Acquired Demyelinating Syndromes

Ina Mexhitaj; Jacqueline Smiler; Fernanda Thompson; Renata Pellegrino Da Silva; Giulia Fadda; E Ann Yeh; Ruth Ann Marrie; Douglas Arnold; Rui Li; Brenda Banwell; Amit Bar-Or

Abstract Text: Approximately 20-30% of children presenting with acquired inflammatory demyelinating syndromes (ADS) have multiple sclerosis (MS). Another 30% harbor serum antibodies against myelin oligodendrocyte glycoprotein and are referred to as having MOG-associated disease (MOGAD). While MS and MOGAD can have similar features, differences in response to immune therapies point to distinct underlying immune mechanisms.
We aimed to assess potentially distinct immune mechanisms underlying MS and MOGAD and applied proteogenomics to high quality cryopreserved peripheral blood mononuclear cells collected from patients with ADS prior to institution of immune therapy, as well as from healthy controls. CITE-seq profiling recovered 104,200 single cells total from 24 children (6 healthy donors; 6 with ADS but neither MS or MOGAD; 6 with MOGAD; and 6 with MS, ascertained with long-term follow-up). Comparative analyses revealed features within the T-cell compartment that differed between children with MS and MOGAD. Specifically, the CD4 T-cell compartment in children with MS (when compared to MOGAD) was enriched for a memory population with a Th1-like phenotype and enriched for a Th17-like memory population expressing surface VLA-4 components. CD8 effector T cells in children with MS (when compared to MOGAD) were enriched for the checkpoint-molecule TIGIT. The CD4 T-cell and CD8 T-cell compartments in children with MOGAD (when compared to MS) were enriched for an interferon-response gene-expression signature. Overall, our study points to distinct features of circulating cellular immune profiles in children with MS and MOGAD and provides novel insights into early immune mechanisms that may be involved in each of these conditions.