The elimination of circulating Epstein-Barr virus infected B cells underlies anti-CD20 monoclonal antibody activity in multiple sclerosis: A hypothesis.

Multiple sclerosis is a chronic immune-mediated disease of the central nervous system that has aspects of repetitive inflammatory activity as well as a slow neurodegenerative process. The immune assault on the nervous system is triggered by a complex interaction between immunogenetic and environmental factors. Among the different environmental factors, a compelling case, buttressed by strong epidemiological, serological and other data, has been made for the role of Epstein-Barr virus (EBV) in the pathogenesis of MS. However, the ubiquity of EBV, lack of a well understood role in MS pathogenesis, and controversies regarding its presence in brains of people with MS has caused debate as to how exactly it contributes to MS. Recent years have seen the remarkable effect of anti-CD20 therapies on the inflammatory component of MS. How B cell depletion results in a salutary effect in MS remains incompletely understood. It has been proposed that depletion of CD20+ B-cells disrupts other pro-inflammatory pathways in the immune system, especially T-cells. In this paper, we make the case that the robust effect of anti-CD20 therapies on MS activity could actually be from removal of circulating EBV-infected memory B-cells that drive CNS inflammation and not through other immune pathways - in essence that this is from an anti-viral effect, and not necessarily an immuno-modulatory effect.