High-dose dexamethasone shifts the balance of stimulatory and inhibitory Fcγ receptors on monocytes in patients with primary immune thrombocytopenia
High-dose dexamethasone shifts the balance of stimulatory and inhibitory Fcγ receptors on monocytes in patients with primary immune thrombocytopenia
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DOI：
10.1182/blood-2010-07-295477
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发表时间：
2011-02-10
期刊：
影响因子：
20.3
通讯作者：
Peng, Jun
中科院分区：
文献类型：
--
作者：
Liu, Xin-guang;Ma, Shi-hui;Peng, Jun
人的Fc-Gamma受体(Fc-Gamma R)系统由两个对立的家族组成，即激活的Fc-Gamma R(Fc-Gamma RI、Fc-Gamma RIia和Fc-Gamma RIII)和抑制性Fc-Gamma R(Fc-Gamma RIIb)。激活和抑制Fc-γ受体的平衡失调参与了许多自身免疫性疾病的发病机制。本研究检测了23例原发性免疫性血小板减少症(ITP)患者大剂量地塞米松(HD-DXM)治疗前后单核细胞表面Fc-γ受体的表达。ITP患者Fc-Gamma RI表达明显升高，HD-DXM治疗后Fc-Gamma RI表达降低。初治患者单核细胞表面Fc-Gamma、RIIA/IIb基因表达比值明显高于正常对照组。HD-DXM治疗后，上述比例降低，Fc-Gamma RIIb基因和蛋白表达增加，同时Fc-Gamma RIIA、Fc-Gamma RI表达和单核细胞吞噬能力显著降低。单核细胞表面Fc-γ-RIII的表达在患者组和对照组之间无显著差异。体外细胞培养实验表明，地塞米松可诱导ITP患者单核细胞表达Fc-Gamma RIIA和Fc-Gamma RIIb，且Fc-Gamma RIIb的表达幅度较高。提示Fc-Gamma-R平衡失调可能在ITP的发病机制中起一定作用，HD-DXM治疗可使ITP患者单核细胞Fc-Gamma-R平衡向抑制性Fc-Gamma-RIIb方向移动。(血。2011；117(6)：2061-2069)
The human Fc gamma receptor (Fc gamma R) system is composed of 2 opposing families, the activating Fc gamma Rs (Fc gamma RI, Fc gamma RIIa, and Fc gamma RIII) and the inhibitory Fc gamma R (Fc gamma RIIb). The disturbed balance of the activating and inhibitory Fc gamma Rs has been implicated in the pathogenesis of many autoimmune diseases. In this study, the expression of Fc gamma Rs on monocytes was determined in 23 patients with primary immune thrombocytopenia (ITP) before and after high-dose dexamethasone (HD-DXM) treatment. The Fc gamma RI expression was significantly higher in ITP patients and decreased after HD-DXM treatment. The ratio of Fc gamma RIIa/IIb mRNA expression on monocytes was significantly higher in untreated patients than in healthy controls. After HD-DXM therapy, the ratio decreased and the increased expression of Fc gamma RIIb mRNA and protein coincided with a remarkable decrease in the expression of Fc gamma RIIa, Fc gamma RI, and monocyte phagocytic capacity. There was no significant difference in Fc gamma RIII expression on monocytes between patients and controls. In vitro cell-culture experiments showed that DXM could induce Fc gamma RIIa and Fc gamma RIIb expression in monocytes from ITP patients, with Fc gamma RIIb at higher amplitudes. These findings suggested that the disturbed Fc gamma R balance might play a role in the pathogenesis of ITP, and that HD-DXM therapy could shift monocyte Fc gamma R balance toward the inhibitory Fc gamma RIIb in patients with ITP. (Blood. 2011; 117(6): 2061-2069)