A few years ago a couple of papers appearred that sent the MS World EBV mad and it awakened the idea that Epstein Barr Virus is in the causal pathway of MS. It was then suggested that antibodies to EBV cross react with glial proteins as the root cause…Whilst this process may be plausible the target on glia identified is about as likely as it is for Leeds United to win the football premiership this year. However this gave the idea that MS is an antibody mediated disease after years of being told it was a T cell mediated disease. This study looks at anti-EBV antibodies after ocrelizumab and concludes that there is no change that can be correlated by clinical disease….Is this the end of the causal EBV idea?
I say this is what the biology suggests, with ocrelizumab there is a loss of circulating IgM and then IgG antibody. However ocrelizumab is continually killing B cells that will make IgM and IgG against virus and bacteria that are infecting us all the time. However ocrelizumab does not target antibody producing cells once they have been made and so you would not expect to see your antibody responses to EBV and cytomegalo virus which will have been generated long before people take ocrelizumab. I was talking about MS drugs and someone said what is happening with dealling with EBV. I said there are numerous studies ongoing that aim to do this but I also suggested the design may be key….If EBV is the trigger for MS it may be too late to do anything in people who already have the condition and if this is the issue then yu have to deal with the virus before one gets MS…If ebv precipitates MS then in may do something. I said time will tell but if there are lots of trial failures people will lose interest so best to get the approach right sooner rather than later.
Esposito A, Corsaro L, Delle Cave I, Nicolella V, Palladino R, Affinito G, Selvaggi F, Petracca M, Carotenuto A, Lanzillo R, Portella G, Castaldo G, Brescia Morra V, Moccia M. Anti-EBV antibody reduction during ocrelizumab treatment is not associated with multiple sclerosis outcomes. Mult Scler Relat Disord. 2025 Nov 1;104:106830. doi: 10.1016/j.msard.2025.106830.
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.
Source: multiple-sclerosis-research.org