Increased Expressions of OX40 and OX40 Ligand in Patients with Primary Immune Thrombocytopenia
Increased Expressions of OX40 and OX40 Ligand in Patients with Primary Immune Thrombocytopenia
复制标题
原发性免疫性血小板减少症患者 OX40 和 OX40 配体表达增加
DOI：
10.1155/2019/6804806
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发表时间：
2019-01-01
影响因子：
4.1
通讯作者：
Xie, Jue
中科院分区：
文献类型：
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作者：
Cui, Dawei;Lv, Yan;Xie, Jue
研究背景OX40又称肿瘤坏死因子受体超家族成员4（TNFRSF4），其配体（OX40L）在自身免疫性疾病的发病机制中起重要作用。免疫性血小板减少症（ITP）是一种出血性自身免疫性疾病，其特征是血小板计数低，主要由抗血小板自身抗体引起。本研究首先探讨OX40和OX40L在ITP发病中的临床意义。方法选择54例初诊ITP患者和24例健康对照者。流式细胞术分析OX40+CD4 + T细胞占CD4+T细胞的百分比，实时荧光定量PCR分析OX40和OX40L mRNA的表达水平。通过ELISA分析血浆可溶性OX40 L（sOX40 L）水平，通过固相技术分析血浆抗血小板自身抗体水平。结果ITP患者外周血中OX40+CD4+T细胞比例较HC明显增高，且抗血小板自身抗体阳性者较抗血小板自身抗体阴性者增高更明显。在抗血小板自身抗体阳性的患者中，OX40+CD4+T细胞频率升高与血小板计数降低呈负相关。ITP患者的血浆sOX40 L水平显著高于HC患者，并且与抗血小板自身抗体阴性的患者相比，抗血小板自身抗体阳性的患者血浆sOX40 L水平升高。在抗血小板自身抗体阳性的患者中，血浆sOX40 L水平与血小板计数降低呈负相关。ITP患者PBMC中OX40和OX40L的mRNA表达水平也显著高于HC，且抗血小板自身抗体阳性和阴性的ITP患者OX40和OX40L的表达水平差异有统计学意义。结论OX40和OX40L的高表达参与了ITP的发病过程，OX40和OX40L可能是治疗ITP的有效靶点。
Background OX40, which is also known as tumor necrosis factor receptor superfamily member 4 (TNFRSF4), and its ligand (OX40L) play a critical role in the pathogenesis of autoimmune diseases. Immune thrombocytopenia (ITP), a hemorrhagic autoimmune disorder, is characterized by low platelet counts that are predominantly caused by antiplatelet autoantibodies. In this study, we firstly investigated the clinical significance of OX40 and OX40L expression in the pathogenesis of ITP in patients. Methods Fifty-four newly diagnosed ITP patients and 24 healthy controls (HCs) were enrolled in this study. The percentage of OX40+CD4+T cells among CD4+T cells was analyzed by flow cytometry, and the expression levels of OX40 and OX40L mRNA were analyzed by quantitative real-time PCR. Plasma soluble OX40L (sOX40L) levels were analyzed by ELISA, and plasma levels of antiplatelet autoantibodies were analyzed by a solid-phase technique. Results Compared with HCs, the frequencies of OX40+CD4+T cells were significantly increased in ITP patients, particularly in patients with positive antiplatelet autoantibodies compared to those with negative antiplatelet autoantibodies. The elevated frequencies of OX40+CD4+T cells were negatively correlated with low platelet counts in patients with positive antiplatelet autoantibodies. Plasma sOX40L levels in ITP patients were significantly greater than those in HCs and increased in patients with positive antiplatelet autoantibodies compared to those with negative antiplatelet autoantibodies. Plasma sOX40L levels were negatively correlated with low platelet counts in patients with positive antiplatelet autoantibodies. Additionally, the mRNA expression levels of OX40 and OX40L in PBMCs from ITP patients were also notably greater than those from HCs, and the expression levels of OX40 and OX40L were significantly different in ITP patients with positive and negative antiplatelet autoantibodies. Conclusion These data indicated that increased expression levels of OX40 and OX40L were involved in the pathogenesis of ITP, and OX40 and OX40L may be valuable therapeutic targets for ITP.