Zekiye Firat, Duygu Ozkan Yasargun, Vuslat Yilmaz, Recai Turkoglu, Erdem Tuzun, Erdil Arsoy
Journal of Multiple Sclerosis Research - 2026;6(1):39-45
Objective: Multiple sclerosis (MS) is a chronic, immune-mediated disorder of the central nervous system with a heterogeneous clinical course. Patients presenting with a first episode of optic neuritis (ON) generally exhibit a more favorable prognosis. Although T lymphocytes have traditionally been regarded as the primary drivers of MS pathogenesis, increasing evidence highlights the importance of B lymphocytes and their intracellular signaling pathways. This study aimed to investigate whether differences exist in B-cell-related intracellular pathway gene expression between patients with MS with and without ON onset and to assess their potential pathogenic implications. Materials and Methods: A total of 26 patients with MS were enrolled, including 10 with ON onset and 16 without ON at disease onset. Disability was evaluated using the Expanded Disability Status Scale (EDSS), and cognitive performance was assessed using standardized neuropsychological testing. Peripheral blood samples were analyzed for B-cell-related gene expression [B-lymphoid tyrosine kinase (BLK), B-cell scaffold protein with ankyrin repeats 1 (BANK1), transforming growth factor beta (TGFB), and ATPase Na+/K+ transporting subunit beta 3 (ATP1B3)] using quantitative polymerase chain reaction, and immune cell subset ratios were evaluated using flow cytometry. Results: Although patients with ON-onset MS experienced a higher number of ON attacks during disease course, they demonstrated EDSS scores comparable to those of patients without ON onset. No significant differences were observed in immune cell subset ratios or in BLK, BANK1, or TGFB expression levels. However, ATP1B3 expression was significantly reduced in patients with ON onset compared with those without ON onset (p=0.011). Conclusion: Reduced expression of ATP1B3, a gene implicated in B lymphocyte proliferation, appears to be associated with ON onset and increased frequency of ON attacks. These findings suggest that ATP1B3 may be a potential biomarker associated with ON occurrence in MS. This hypothesis requires validation in larger longitudinal cohorts.
