From the Danish Multiple Sclerosis Center (M.R.E., R.H.H., C.H., C.A., F.S.), Department of Neurology, Rigshospitalet, University of Copenhagen, Glostrup, Denmark; and Department of Neurology with Institute of Translational Neurology (H.W.), University Hospital Münster, Germany.
Neurol Neuroimmunol Neuroinflamm. 2022 Jun 7;9(4). doi: 10.1212/NXI.0000000000200004. Print 2022 Jul.
The anti-CD20 antibody ofatumumab is an efficacious therapy for multiple sclerosis (MS) through depletion of B cells. The purpose of this study was to examine the derivative effects of B cell depletion on the peripheral immune system and a direct treatment effect on T cells expressing CD20.
Frequency and absolute numbers of peripheral leukocytes of treatment-naive patients with relapsing-remitting MS (RRMS) and patients treated with ofatumumab for a mean of 482 days were assessed in this observational study by flow cytometry. In addition, effector function and CNS migration of T cells using a human in vitro blood-brain barrier (BBB) assay were analyzed.
This study showed that ofatumumab treatment of patients with RRMS increased the control of effector T cells and decreased T cell autoreactivity. It also showed that ofatumumab reduced the level of peripheral CD20 T cells and that the observed decrease in CNS-migratory capacity of T cells was caused by the depletion of CD20 T cells. Finally, our study pointed out a bias in the measurement of CD20 cells due to a steric hindrance between the treatment antibody and the flow cytometry antibody.
The substantial ofatumumab-induced alteration in the T cell compartment including a severely decreased CNS-migratory capacity of T cells could partly be attributed to the depletion of CD20 T cells. Therefore, we propose that depletion of CD20 T cells contributes to the positive treatment effect of ofatumumab and suggests that ofatumumab therapy should be considered a B cell and CD20 T cell depletion therapy.
This study provides Class IV evidence that compared with treatment-naive patients, ofatumumab treatment of patients with RRMS decreases peripheral CD20 T cells, increases effector T cell control, and decreases T cell autoreactivity.
抗 CD20 抗体奥法妥木单抗通过耗竭 B 细胞，是一种治疗多发性硬化症（MS）的有效疗法。本研究旨在研究 B 细胞耗竭对周围免疫系统的衍生影响以及对表达 CD20 的 T 细胞的直接治疗作用。
通过流式细胞术评估了这项观察性研究中，未经治疗的复发缓解型多发性硬化症（RRMS）患者和接受奥法妥木单抗治疗平均 482 天的患者的外周白细胞频率和绝对数量。此外，还通过体外血脑屏障（BBB）模型分析了 T 细胞的效应功能和中枢神经系统迁移。
本研究表明，奥法妥木单抗治疗 RRMS 患者可增强效应 T 细胞的控制作用，并降低 T 细胞自身反应性。还表明奥法妥木单抗降低了外周 CD20 T 细胞的水平，观察到 T 细胞向中枢神经系统迁移能力的降低是由 CD20 T 细胞耗竭引起的。最后，我们的研究指出了由于治疗抗体和流式细胞术抗体之间的空间位阻，导致对 CD20 细胞的测量存在偏差。
奥法妥木单抗引起的 T 细胞群的实质性改变，包括 T 细胞向中枢神经系统迁移能力的严重降低，部分归因于 CD20 T 细胞的耗竭。因此，我们提出 CD20 T 细胞的耗竭有助于奥法妥木单抗的积极治疗效果，并表明奥法妥木单抗治疗应被视为 B 细胞和 CD20 T 细胞耗竭治疗。
本研究提供了 IV 级证据，与未经治疗的患者相比，奥法妥木单抗治疗 RRMS 患者可降低外周 CD20 T 细胞，增强效应 T 细胞的控制作用，并降低 T 细胞自身反应性。
