期刊
NEUROLOGY-NEUROIMMUNOLOGY & NEUROINFLAMMATION
卷 9, 期 4, 页码 -出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1212/NXI.0000000000200004
关键词
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资金
- Aase and Ejnar Danielsen Foundation
- Laege Sofus Carl Emil Friis and Wife Olga Friis' Grant
- Jascha Foundation
- Toyota Foundation
- A.P. Moller Foundation
- Foundation for Research in Neurology
- Research Board at Copenhagen University Hospital, Rigshospitalet
This study shows that ofatumumab treatment is effective in controlling effector T cells and reducing T cell autoreactivity in patients with RRMS. It also demonstrates that ofatumumab reduces the level of peripheral CD20(+) T cells and decreases the CNS-migratory capacity of T cells.
Background and Objectives 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. Methods 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. Results 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. Discussion 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. Classification of Evidence 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.
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