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奥法妥木单抗治疗开始后 CD20 B 和 T 细胞迅速耗竭。

Rapid depletion of CD20 B and T cells following ofatumumab therapy onset.

机构信息

Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.

Department of Rheumatology and Clinical Immunology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.

出版信息

Mult Scler Relat Disord. 2024 Nov;91:105886. doi: 10.1016/j.msard.2024.105886. Epub 2024 Sep 14.

Abstract

BACKGROUND

The humanized monoclonal anti-CD20-antibody ofatumumab is highly effective in treating relapsing multiple sclerosis (MS).

OBJECTIVE

This study aimed to investigate the immanent effect of ofatumumab on the peripheral immune system, particularly targeting B and T cells expressing CD20.

METHODS

Blood samples of 53 MS patients receiving ofatumumab were collected prior to first application and after one week, two weeks and three months. Multicolor flow cytometry was used to phenotype peripheral blood mononuclear cells, and immunoglobulin (Ig) concentrations were measured by nephelometry.

RESULTS

Among CD20 lymphocytes, 13 % co-expressed CD3 (identifying them as CD3CD20 T lymphocytes), with a noticeable shift in the CD4/CD8-ratio towards CD8 T cells. One week after administering ofatumumab, a significant reduction of CD20 lymphocytes with complete depletion of CD3CD20 T lymphocytes was observed, persisting during the investigation period. During the treatment, IgM levels showed a slight but significant decrease, whereas IgA and IgG levels remained stable.

CONCLUSION

Ofatumumab effectively depletes CD20 lymphocytes already after the first administration. This depletion affects not only B cells, but also a small proportion of T cells (CD3CD20), affirming the hypothesis that the anti-inflammatory effects of CD20 cell depletion might extend to the reduction of CD3CD20 T lymphocytes.

摘要

背景

人源化单克隆抗 CD20 抗体奥法妥木单抗在治疗复发型多发性硬化症(MS)方面非常有效。

目的

本研究旨在探讨奥法妥木单抗对周围免疫系统的内在影响,特别是针对表达 CD20 的 B 细胞和 T 细胞。

方法

收集了 53 名接受奥法妥木单抗治疗的 MS 患者的血液样本,在首次应用前和应用后一周、两周和三个月进行采集。采用多色流式细胞术对外周血单个核细胞进行表型分析,并通过散射光比浊法测量免疫球蛋白(Ig)浓度。

结果

在 CD20 淋巴细胞中,有 13%共同表达 CD3(将其鉴定为 CD3CD20 T 淋巴细胞),CD4/CD8 比值向 CD8 T 细胞显著转移。奥法妥木单抗给药后一周,观察到 CD20 淋巴细胞显著减少,CD3CD20 T 淋巴细胞完全耗竭,在整个研究期间持续存在。在治疗期间,IgM 水平略有但显著下降,而 IgA 和 IgG 水平保持稳定。

结论

奥法妥木单抗在首次给药后即可有效耗竭 CD20 淋巴细胞。这种耗竭不仅影响 B 细胞,还影响一小部分 T 细胞(CD3CD20),证实了 CD20 细胞耗竭的抗炎作用可能扩展到减少 CD3CD20 T 淋巴细胞的假说。

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