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.

B 细胞耗竭疗法已被证明对多发性硬化症 (MS) 有益。然而，B 细胞耗竭介导其在 MS 中的有益作用的机制仍不清楚。为了更好地了解 B 细胞耗竭如何使患有以前被认为主要由 CD4 T 细胞介导的疾病的患者受益，在超过 18 个时间点的 ublituximab（一种糖工程化 CD20 单克隆抗体）的 II 期试验中监测了 48 名患者的免疫特征一年。正如我们之前所描述的，在 ublituximab 初始剂量后，T 细胞、NK 细胞和骨髓细胞的百分比发生了显着变化，但这种变化在一周内恢复正常，并且这些群体在研究期间保持稳定。然而，T 细胞亚群随着初始 CD4 和 CD8 T 细胞百分比的增加以及记忆 T 细胞的减少而发生变化。重要的是，Th1 和 CD4 的百分比⁺ GM-CSF ⁺ T 细胞减少，而 Treg 的百分比在一年中继续增加。Ublituximab 不仅消耗了 CD20 ⁺ B 细胞，还消耗了CD20 ⁺ T 细胞。T 细胞亚群的有利变化可能有助于 B 细胞耗竭疗法的有益效果。