A-to-I RNA editing profiles and distinct immune responses in myelin oligodendrocyte glycoprotein antibody-positive optic neuritis

Abstract

Myelin oligodendrocyte glycoprotein antibody-positive optic neuritis (MOG-ON) is an autoimmune inflammatory demyelinating disorder of the optic nerve that often results in severe visual impairment and recurrent attacks. Although immune dysregulation is recognized as a central feature of MOG-ON, the contribution of post-transcriptional regulatory mechanisms, particularly adenosine-to-inosine (A-to-I) RNA editing, to disease pathogenesis and visual outcomes remains poorly understood. In this study, we characterized A-to-I RNA editing in MOG-ON, investigated molecular signatures and immune responses across the acute and remission phases, and explored candidate genes and associations with visual outcomes. A total of 14 peripheral blood samples were collected from patients with MOG-ON (9 in the acute phase and 5 in remission) and from 7 healthy controls. The A-to-I editome was characterized using RNA editing profiling, and stage-associated molecular signatures and immune responses were investigated using transcriptomic sequencing. In addition, functional enrichment analysis, immune pathway profiling, and estimated immune-cell proportions analysis were performed. MOG-ON exhibited extensive A-to-I RNA editing remodeling, with 240 candidate differentially edited sites across 135 genes, predominantly enriched in neutrophil-mediated immunity and T-cell differentiation. Transcriptomic analysis revealed distinct stage-associated molecular programs: immunoglobulin production and B-cell receptor signaling were enriched during the acute phase, whereas cell cycle regulation was predominant during remission. CD74 and CDK1 were identified as candidate hub genes in the acute and remission phases, respectively. Furthermore, exploratory analyses suggested nominal associations of acute-phase BCVA with proportions of regulatory T cells and of CD74 expression with estimated neutrophil and monocyte proportions. Collectively, these findings characterize RNA-editing alterations and stage-associated immune-transcriptomic features in MOG-ON and provide hypothesis-generating molecular candidates for further investigation.