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在多发性硬化症中,奥瑞珠单抗比利妥昔单抗更能消耗T淋巴细胞。

Ocrelizumab depletes T-lymphocytes more than rituximab in multiple sclerosis.

作者信息

Capasso Nicola, Nozzolillo Agostino, Scalia Giulia, Lanzillo Roberta, Carotenuto Antonio, De Angelis Marcello, Petruzzo Martina, Saccà Francesco, Russo Cinzia Valeria, Brescia Morra Vincenzo, Moccia Marcello

机构信息

Multiple Sclerosis Clinical Care and Research Centre, Department of Neuroscience, Reproductive Sciences and Odontostomatology, University of Naples Federico II, Naples, Italy.

Centre for Advanced Biotechnology (CEINGE), Naples, Italy.

出版信息

Mult Scler Relat Disord. 2021 Apr;49:102802. doi: 10.1016/j.msard.2021.102802. Epub 2021 Jan 28.

DOI:10.1016/j.msard.2021.102802
PMID:33556652
Abstract

BACKGROUND

We aim to directly compare changes in lymphocyte subpopulations between chimeric (rituximab) and humanised (ocrelizumab) anti-CD20 antibodies in multiple sclerosis (MS).

METHODS

In this retrospective analysis of prospectively collected data, we included 88 patients with MS, treated with rituximab (n=50) or ocrelizumab (n=38). We used flow cytometry in the peripheral blood to count total lymphocytes and lymphocytes expressing different phenotypic markers (CD4, CD8, CD19, CD20, CD4/CD8 ratio), before treatment and after 1, 3 and 6 months.

RESULTS

On linear mixed effect regression models, after 1, 3 and 6 months, patients treated with rituximab and with ocrelizumab were similar in total lymphocyte count, CD19 lymphocytes, CD20 lymphocytes and CD4/CD8 ratio. However, patients treated with ocrelizumab presented with lower CD4 T lymphocytes and CD8 T lymphocytes after 1, 3 and 6 months (all p<0.05). No between-treatment difference in EDSS progression was found.

DISCUSSION

B-cell levels in the peripheral blood were equally decreased by rituximab and ocrelizumab. On the contrary, CD4 and CD8 T lymphocyte reduction was more pronounced in ocrelizumab, when compared with rituximab, suggesting a broader immunomodulatory effect for the humanised antibody to be confirmed and correlated with clinical efficacy in the long term.

摘要

背景

我们旨在直接比较嵌合型(利妥昔单抗)和人源化(奥瑞珠单抗)抗CD20抗体在多发性硬化症(MS)中淋巴细胞亚群的变化。

方法

在这项对前瞻性收集数据的回顾性分析中,我们纳入了88例接受利妥昔单抗(n = 50)或奥瑞珠单抗(n = 38)治疗的MS患者。我们使用流式细胞术对外周血中的总淋巴细胞以及表达不同表型标志物(CD4、CD8、CD19、CD20、CD4/CD8比率)的淋巴细胞进行计数,分别在治疗前以及治疗后1、3和6个月进行检测。

结果

在线性混合效应回归模型中,在1、3和6个月后,接受利妥昔单抗和奥瑞珠单抗治疗的患者在总淋巴细胞计数、CD19淋巴细胞、CD20淋巴细胞和CD4/CD8比率方面相似。然而,接受奥瑞珠单抗治疗的患者在1、3和6个月后CD4 T淋巴细胞和CD8 T淋巴细胞水平较低(所有p<0.05)。未发现治疗组间在扩展残疾状态量表(EDSS)进展方面存在差异。

讨论

外周血中的B细胞水平被利妥昔单抗和奥瑞珠单抗同等程度地降低。相反,与利妥昔单抗相比,奥瑞珠单抗对CD4和CD8 T淋巴细胞的减少更为明显,这表明这种人源化抗体具有更广泛的免疫调节作用有待长期证实并与临床疗效相关联。

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