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利妥昔单抗和地塞米松对原发性免疫性血小板减少症患者调节性和促炎性 B 细胞亚群的影响。

Effects of rituximab and dexamethasone on regulatory and proinflammatory B-cell subsets in patients with primary immune thrombocytopenia.

机构信息

Institute for Inflammation Research, Center for Rheumatology and Spine Diseases, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.

Department of Hematology, Roskilde Hospital, Copenhagen, Denmark.

出版信息

Eur J Haematol. 2018 Jan;100(1):45-52. doi: 10.1111/ejh.12978. Epub 2017 Oct 18.

Abstract

OBJECTIVE

To investigate the cytokine production and surface marker composition of B cells in adult patients with newly diagnosed primary immune thrombocytopenia (ITP) before and 12 months after treatment with rituximab + dexamethasone (RTX+DXM) or dexamethasone (DXM).

METHODS

Peripheral blood mononuclear cells were isolated from nine patients treated with RTX+DXM, seven patients treated with DXM, and seven healthy donors. Expression of the cell-surface markers CD5, CD27, CD25, and CD19, and intracellular content of IL-6 and IL-10 were measured by flow cytometry.

RESULTS

PBMCs from ITP patients at baseline contained a lower proportion of IL-10 B cells (P < .01) and IL-6 B cells (P < .01) than healthy controls. All patients responded to therapy and levels were normalized at 12 months. The proportion of CD5 B cells increased (P < .01) and CD27 memory B cells decreased (P < .05) 12 months after treatment with RTX+DXM compared to baseline, with an inverse correlation between platelet numbers and the proportion of CD27 B cells (R = -0.71; P < .05).

CONCLUSION

Both treatment regimens normalized the frequencies of cytokine-producing B cells. The additional increase in CD5 B cells after RTX+DXM is compatible with induction of Bregs.

摘要

目的

研究利妥昔单抗+地塞米松(RTX+DXM)或地塞米松(DXM)治疗初诊成人原发免疫性血小板减少症(ITP)患者治疗前后 B 细胞细胞因子产生和表面标志物组成。

方法

从接受 RTX+DXM 治疗的 9 例患者、接受 DXM 治疗的 7 例患者和 7 例健康供者中分离外周血单个核细胞。通过流式细胞术测量细胞表面标志物 CD5、CD27、CD25 和 CD19 的表达以及细胞内 IL-6 和 IL-10 的含量。

结果

ITP 患者基线时的 PBMC 中 IL-10 B 细胞(P<.01)和 IL-6 B 细胞(P<.01)比例低于健康对照者。所有患者均对治疗有反应,12 个月时水平恢复正常。与基线相比,RTX+DXM 治疗 12 个月后 CD5 B 细胞的比例增加(P<.01),CD27 记忆 B 细胞的比例下降(P<.05),血小板计数与 CD27 B 细胞比例呈负相关(R=-0.71;P<.05)。

结论

两种治疗方案均使细胞因子产生 B 细胞的频率正常化。RTX+DXM 后 CD5 B 细胞的额外增加与 Bregs 的诱导一致。

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