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Ocrelizumab Depletes CD20+ T Cells in Multiple Sclerosis Patients

机译:Ocrelizumab消耗多发性硬化症患者的CD20 + T细胞

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摘要

Ocrelizumab, a humanized monoclonal anti-CD20 antibody, has shown pronounced effects in reduction of disease activity in multiple sclerosis (MS) patients and has recently been approved for the treatment of patients with relapsing MS (RMS) and primary progressive MS (PPMS). CD20 is mainly expressed by B cells, but a subset of T cells (CD3+CD20+ T cells) also expresses CD20, and these CD20+ T cells are known to be a highly activated cell population. The blood of MS patients was analyzed with multicolor flow cytometry before and two weeks after treatment with ocrelizumab regarding the phenotype of peripheral blood mononuclear cells. CD20-expressing CD3+ T cells were found in blood samples of all MS patients, accounted for 2.4% of CD45+ lymphocytes, and constituted a significant proportion (18.4%) of all CD20+ cells. CD3+CD20+ T cells and CD19+CD20+ B cells were effectively depleted two weeks after a single administration of 300 mg ocrelizumab. Our results demonstrate that treatment with ocrelizumab does not exclusively target B cells, but also CD20+ T cells, which account for a substantial amount of CD20-expressing cells. Thus, we speculate that the efficacy of ocrelizumab might also be mediated by the depletion of CD20-expressing T cells.
机译:Ocrelizumab是一种人源化单克隆抗CD20抗体,已显示出在多发性硬化症(MS)患者中降低疾病活性的显着效果,并且最近被批准用于治疗复发性MS(RMS)和原发性进行性MS(PPMS)的患者。 CD20主要由B细胞表达,但一部分T细胞(CD3 + CD20 + T细胞)也表达CD20,而这些CD20 + 已知T细胞是高度活化的细胞群。在用ocrelizumab治疗前和治疗后两周用多色流式细胞仪分析了MS患者的血液,以分析其外周血单个核细胞的表型。在所有MS患者的血液样本中均发现了表达CD20的CD3 + T细胞,占CD45 + 淋巴细胞的2.4%,在CD45 + 淋巴细胞中所占比例很高(18.4%)。所有CD20 + 细胞。一次给药两周后,CD3 + CD20 + T细胞和CD19 + CD20 + B细胞被有效清除300 mg ocrelizumab。我们的结果表明,使用ocrelizumab的治疗不仅针对B细胞,而且还针对CD20 + T细胞,而CD20 + T细胞占CD20表达细胞的大部分。因此,我们推测ocrelizumab的功效也可能由表达CD20的T细胞的消耗介导。

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