Anti-EBV antibody reduction during ocrelizumab treatment is not associated with multiple sclerosis outcomes

Background: The pathogenesis of multiple sclerosis (MS) involves genetic, environmental and immunological aspects. Epstein-Barr virus (EBV) infection is recognized as a major risk factor for MS, potentially contributing through infection and transformation of CD20 B cells. Monoclonal antibodies targeting CD20, such as ocrelizumab, may exert therapeutic effects by depleting memory B cells harbouring latent EBV. Objective: We aim to evaluate changes in serum anti-EBV immunoglobulin G (IgG) titres and clinical correlates during ocrelizumab treatment. Methods: We analysed serum samples from 58 patients treated with ocrelizumab, with levels of total IgG, anti-CMV IgG, and anti-EBV IgG before treatment initiation and after mean follow-up of 4.8 ± 1.5 years. Statistical analyses included paired t-tests to evaluate longitudinal changes in antibody levels, and linear regression models to investigate associations between IgG changes and relapse occurrence, MRI activity, EDSS progression and their combination. Results: Over 4.8 ± 1.5 years, we observed significant reductions in anti-EBV IgG (percentage mean change -8.2%, p = 0.03), comparable to the decline in total IgG (-8.8%, p < 0.01) and anti-CMV IgG (-7.8%, p < 0.01). No significant associations were identified between changes in anti-EBV IgG and different outcomes. Conclusions: Ocrelizumab treatment was associated with reductions in total, anti-EBV and anti-CMV IgGs. Antibody-mediated response to EBV was not associated with disease worsening.