Institute for Inflammation Research, Center for Rheumatology and Spine Diseases, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
Department of Hematology, Roskilde Hospital, Copenhagen, Denmark.
Eur J Haematol. 2018 Jan;100(1):45-52. doi: 10.1111/ejh.12978. Epub 2017 Oct 18.
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).
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.
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).
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.
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。
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。
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)。
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。