A new study set out to assess potentially distinct immune mechanisms underlying multiple sclerosis and myelin oligodendrocyte glycoprotein-associated disease. The findings point to distinct features of circulating cellular immune profiles in children with MS and MOG-associated disease and provides novel insights into early immune mechanisms that may be involved in each of these conditions.

Approximately 20 to 30 percent of children with acquired inflammatory demyelinating syndromes have MS. Another 30 percent harbor antibodies against MOGAD. While MS and MOGAD can have similar features, differences in response to immune therapies point to distinct underlying immune mechanisms.

Researchers at the University of Pennsylvania, the Center for Applied Genomics at the Children's Hospital of Philadelphia, McGill University, in Montreal, the Hospital for Sick Children, in Toronto, and the University of Manitoba, in Winnipeg, analyzed blood cells collected from patients with ADS prior to the application of immune therapy, as well as from healthy controls. CITE-Seq profiling recovered a total of 104,200 single cells with equal contribution from 24 children (six healthy donors; six with ADS but neither MS nor MOGAD; six with MOGAD; and six 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:
 

• When compared to MOGAD, the CD4 T-cell compartment in children with MS was enriched for a memory population with a Th1-like phenotype and enriched for a Th17-like memory population expressing surface components for VLA-4. 
• When compared to MOGAD, within the CD8 compartment, CD8 effector T cells in children with MS were enriched for the checkpoint-molecule TIGIT. 
• Finally, when compared to MS, CD8+ and CD4+ T cell populations in children with MOGAD were enriched for transcriptional signatures linked to interferon responses.

The study was presented at the 2023 ACTRIMS forum.