那他珠单抗对循环 B 细胞、调节性 T 细胞和自然杀伤细胞的影响。

Effects of natalizumab on circulating B cells, T regulatory cells and natural killer cells.

机构信息

Department of Neurology, University Clinic Essen, University of Duisburg-Essen, Essen, Germany. norman.putzki @ kssg.ch

出版信息

Eur Neurol. 2010;63(5):311-7. doi: 10.1159/000302687. Epub 2010 May 5.

DOI:10.1159/000302687

PMID:20453514

Abstract

BACKGROUND

Natalizumab is a humanized monoclonal antibody directed against very late activation antigen 4 (VLA-4) and has a potent effect on disease activity in multiple sclerosis. Blockade of VLA-4 with natalizumab may not only interfere with autoimmunological mechanisms but also with central nervous system immune surveillance.

METHODS

Longitudinal ex vivo and in vitro study to determine the effect of natalizumab on the frequency of distinct immune cells and on the frequency and suppressive function of natural CD4+CD25+ regulatory T cells (Tregs).

RESULTS

Natalizumab binding to VLA-4 was more marked for B cells than for T cells (49% reduction in VLA-4-expressing B cells compared to 24.5% reduction of T cells). There was an increase in circulating B cells over T cells (2.6 vs. 1.5 fold, p < 0.001). Natural killer cells increased 1.5-fold (p = 0.01). Natalizumab led to a relative decrease in CD4+CD25+ Tregs from 18.9 to 14.1% (p = 0.04). The impaired suppressive capacity of Tregs was not restored.

CONCLUSION

Natalizumab reduces VLA-4 expression on all investigated immune cells, but changes were most marked for B cells. Further differential effects on immune cells may be relevant to opportunistic central nervous system infections during treatment with natalizumab.

摘要

背景

那他珠单抗是一种针对非常晚期激活抗原 4（VLA-4）的人源化单克隆抗体，对多发性硬化症的疾病活动具有很强的作用。那他珠单抗阻断 VLA-4 不仅可能干扰自身免疫机制，还可能干扰中枢神经系统免疫监视。

方法

进行了纵向的离体和体外研究，以确定那他珠单抗对不同免疫细胞频率以及天然 CD4+CD25+调节性 T 细胞（Tregs）频率和抑制功能的影响。

结果

那他珠单抗与 VLA-4 的结合在 B 细胞上比在 T 细胞上更为明显（与 T 细胞相比，VLA-4 表达的 B 细胞减少了 49%，而 T 细胞减少了 24.5%）。循环 B 细胞的增加超过了 T 细胞（2.6 倍对 1.5 倍，p<0.001）。自然杀伤细胞增加了 1.5 倍（p=0.01）。那他珠单抗导致 CD4+CD25+Tregs 从 18.9%降至 14.1%（p=0.04）。Tregs 的抑制能力受损并未恢复。