Association of high levels of plasma OX40 with acute adult T-cell leukemia.
Association of high levels of plasma OX40 with acute adult T-cell leukemia.
复制标题
高水平血浆 OX40 与急性成人 T 细胞白血病的关联。
DOI：
10.1007/s12185-018-02580-z
复制
发表时间：
2019
影响因子：
2.1
通讯作者：
Fukushima T.
中科院分区：
文献类型：
--
作者：
Tanaka Y;Takahashi Y;Tanaka R;Miyagi T;Saito M;Fukushima T.
OX 40是肿瘤坏死因子受体（TNFR）超家族的成员，在与其自身配体OX 40 L相互作用后共刺激活化的T细胞。人类T细胞白血病病毒1型（HTLV-1）是成人T细胞白血病（ATL）的病原体。已知ATL细胞表达细胞表面OX 40;然而，来自ATL患者的血液样品中可溶性OX 40（sOX 40）的水平是未知的。定量酶联免疫吸附试验（ELISA）显示急性ATL患者血浆中sOX 40水平显著高于无症状HTLV-1携带者和健康供体，并与外周血单个核细胞（PBMC）中sCD 25水平和HTLV-1前病毒载量相关。急性ATL患者新鲜PBMC中OX 40阳性细胞的比例高于携带者，并将sOX 40脱落到培养上清液中。基质金属蛋白酶（MMP）抑制剂GM 6001可部分抑制sOX 40的脱落。sOX 40的一部分能够结合OX 40 L。这些结果表明，在急性ATL患者中，高水平的sOX 40从大量ATL细胞流入血液。因此，异常升高的血浆sOX 40水平可用作急性ATL的额外诊断标志物。
OX40, a member of the tumor necrosis factor receptor (TNFR) superfamily, co-stimulates activated T cells following interaction with its own ligand OX40L. Human T-cell leukemia virus type-1 (HTLV-1) is an etiological agent of adult T-cell leukemia (ATL). ATL cells are known to express cell surface OX40; however, the level of soluble OX40 (sOX40) in blood samples from ATL patients is unknown. Quantitative enzyme-linked immune-sorbent assay (ELISA) showed that sOX40 levels were significantly higher in plasma from acute ATL patients than those from asymptomatic HTLV-1 carriers and healthy donors, and correlated with sCD25 levels and HTLV-1 proviral loads in peripheral blood mononuclear cells (PBMCs). Fresh PBMCs from acute ATL patients showed a higher percentage of OX40-positive cells compared with those from carriers, and shed sOX40 into culture supernatants. Shedding of sOX40 was partially inhibited by a matrix metalloproteinase (MMP) inhibitor, GM6001. A fraction of sOX40 was capable of binding to OX40L. These results suggest that high levels of sOX40 are shed into blood from a large number of ATL cells in acute ATL patients. Thus, abnormally elevated plasma sOX40 levels may be useful as an additional diagnostic marker of acute ATL.