B cell depletion changes the immune cell profile in multiple sclerosis patients: One-year report

Abstract

B cell depletion therapy has been shown to be beneficial in multiple sclerosis (MS). However, the mechanism by which B cell depletion mediates its beneficial effects in MS is still unclear. To better understand how B cell depletion may benefit patients with a disease previously thought to be primarily mediated by CD4 T cells, immune profiles were monitored in 48 patients in a phase II trial of ublituximab, a glycoengineered CD20 monoclonal antibody, at 18 time points over a year. As we previously described there was a significant shift in the percentages of T cells, NK cells, and myeloid cells following the initial dose of ublituximab, but this shift normalized within a week and these populations remained stable for the duration of the study. However, T cell subsets changed with an increase in the percentage of naïve CD4 and CD8 T cells and a decline in memory T cells. Importantly, the percentage of Th1 and CD4⁺GM-CSF⁺ T cells decreased, while the percentage of Tregs continued to increase over the year. Ublituximab not only depleted CD20⁺ B cells, but also CD20⁺ T cells. The favorable changes in the T cell subsets may contribute to the beneficial effects of B cell depletion therapy.

Keywords: B cell; CD20; Multiple sclerosis; Regulatory T cell; T cell; Ublituximab.