“I have been saying for some time now that what differentiates the big boys from the small boys in terms of DMT efficacy is an impact on B cell biology. I have done a matrix of all the disease-modifying therapies and what is common to all the highly-effective therapies is an impact on B cells. The study below shows that fingolimod also has a profound effect on B cell biology; it reduces B cell numbers in the periphery in particular activated B cells. It did not have an impact on plasmablasts. What is so important about B cells that is different to plasmablasts? Plasmablasts are a later down the development pathway of B cells. B cells are responsible for antigen presentation and a host of other roles. B cells are also the cell in which EBV shacks-up. Could the common-denominator be via EBV? Now this is an experiment I have being trying to get done for the best part of a decade.”
Epub: Nakamura et al. Differential effects of fingolimod on B-cell populations in multiple sclerosis. Mult Scler. 2014 Feb.
BACKGROUND: Fingolimod is an oral drug approved for multiple sclerosis (MS) with an ability to trap central memory T cells in secondary lymphoid tissues; however, its variable effectiveness in individual MSers indicates the need to evaluate its effects on other lymphoid cells.
OBJECTIVE: To clarify the effects of fingolimod on B-cell populations in MSers.
METHODS: We analysed blood samples from 9 fingolimod-treated and 19 control MSers by flow cytometry, to determine the frequencies and activation states of naive B cells, memory B cells, and plasmablasts (antibody producing).
RESULTS: The frequencies of each B-cell population in peripheral blood mononuclear cells (PBMC) were greatly reduced 2 weeks after starting fingolimod treatment. Detailed analysis revealed a significant reduction in activated memory B cells, particularly those expressing Ki-67, a marker of cell proliferation. Also, we noted an increased proportion of activated plasmablasts (CD138+) among whole plasmablasts, in the MSers treated with fingolimod.
CONCLUSIONS: The marked reduction of Ki-67+ memory B cells may be directly linked with the effectiveness of fingolimod in treating MS. In contrast, the relative resistance of CD138+ plasmablasts to fingolimod may be of relevance for understanding the differential effectiveness of fingolimod in individual MSers.