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在骨髓增生异常综合征患者中,促红细胞生成素的使用与T细胞特性的改善相关。

Erythropoietin administration is associated with improved T-cell properties in patients with myelodysplastic syndromes.

作者信息

Deshet-Unger Naamit, Oster Howard S, Prutchi-Sagiv Sara, Maaravi Nir, Golishevski Nataliya, Neumann Drorit, Mittelman Moshe

机构信息

Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.

Department of Medicine, Tel Aviv Sourasky Medical Center, Tel Aviv, 64239, and Sackler Faculty of Medicine, Tel Aviv University, Israel.

出版信息

Leuk Res. 2017 Jan;52:20-27. doi: 10.1016/j.leukres.2016.11.002. Epub 2016 Nov 2.

Abstract

The immune system is impaired in myelodysplastic syndromes (MDS) and plays a role in the pathogenesis of the disease. Here we show effects of recombinant human erythropoietin (rHuEPO) on T cell (CD4, CD8 and CD4CD25) number and function in MDS patients. Healthy (20 subjects), MDS patients without rHuEPO treatment ('MDS', 13), and MDS patients treated with rHuEPO ('MDS+EPO', 17) were examined. CD4 and CD8 T cell numbers were reduced and increased respectively in MDS compared to healthy subjects. EPO treatment normalized these levels. CD4CD25 cell numbers, lower in MDS, were normalized in MDS+EPO. In vitro activation of CD4 and CD8 cells with phytohemagglutinin as measured by CD69 expression, demonstrated a 7.2 fold increase in CD4 activation vs 13.6 fold for MDS and MDS+EPO respectively (p=0.004); and 10.2 fold (MDS) vs 18.6 fold (MDS+EPO, p<0.003) for CD8 T cells. Expression of the co-stimulatory marker CD28, decreased in CD4 and CD8 T cells in MDS, was normalized in MDS+EPO CD4 T cells. Subgroup analysis of milder disease (WHO RA and RARS) and more advanced disease revealed no difference in CD4 and CD8 T cell numbers. However, the activation of these cells in the RA/RARS subgroup was impaired in EPO-untreated and enhanced in EPO-treated MDS patients. Our data suggest that EPO treatment improves immune abnormalities in MDS and may depend on disease severity.

摘要

骨髓增生异常综合征(MDS)患者的免疫系统受损,且在该疾病的发病机制中起作用。在此,我们展示了重组人促红细胞生成素(rHuEPO)对MDS患者T细胞(CD4、CD8和CD4CD25)数量及功能的影响。研究对象包括健康受试者(20名)、未接受rHuEPO治疗的MDS患者(“MDS”组,13名)以及接受rHuEPO治疗的MDS患者(“MDS+EPO”组,17名)。与健康受试者相比,MDS患者的CD4和CD8 T细胞数量分别减少和增加。EPO治疗使这些水平恢复正常。MDS患者中较低的CD4CD25细胞数量在MDS+EPO组中恢复正常。用植物血凝素体外激活CD4和CD8细胞,通过CD69表达测量,结果显示CD4细胞激活增加了7.2倍,而MDS组和MDS+EPO组分别增加了13.6倍(p=0.004);CD8 T细胞方面,MDS组增加了10.2倍,MDS+EPO组增加了18.6倍(p<0.003)。共刺激标志物CD28的表达在MDS患者的CD4和CD8 T细胞中降低,而在MDS+EPO组的CD4 T细胞中恢复正常。对病情较轻(世界卫生组织RA和RARS)和病情更严重的患者进行亚组分析,结果显示CD4和CD8 T细胞数量无差异。然而,在未接受EPO治疗的RA/RARS亚组中,这些细胞的激活受损,而在接受EPO治疗的MDS患者中增强。我们的数据表明,EPO治疗可改善MDS患者的免疫异常,且可能取决于疾病严重程度。

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