TY - JOUR

T1 - Ofatumumab Modulates Inflammatory T Cell Responses and Migratory Potential in Patients With Multiple Sclerosis

AU - von Essen, Marina Rode

AU - Hansen, Rikke Holm

AU - Højgaard, Camilla

AU - Ammitzbøll, Cecilie

AU - Wiendl, Heinz

AU - Sellebjerg, Finn

N1 - Publisher Copyright: Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

PY - 2022/7

Y1 - 2022/7

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85131491765&partnerID=8YFLogxK

U2 - 10.1212/NXI.0000000000200004

DO - 10.1212/NXI.0000000000200004

M3 - Journal article

C2 - 35672145

AN - SCOPUS:85131491765

VL - 9

JO - Neurology: Neuroimmunology & Neuroinflammation

JF - Neurology: Neuroimmunology & Neuroinflammation

SN - 2332-7812

IS - 4

M1 - e200004

ER -