Increased ADAM10 expression in patients with immune thrombocytopenia
Increased ADAM10 expression in patients with immune thrombocytopenia
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免疫性血小板减少症患者 ADAM10 表达增加
DOI：
10.1016/j.intimp.2017.12.004
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发表时间：
2018
影响因子：
5.6
通讯作者：
Xu Kailin
中科院分区：
文献类型：
--
作者：
Qiao Jianlin;Luo Qi;Liu Na;Wei Guangyu;Wu Xiaoqing;Lu Jun;Tang Kai;Wu Yulu;Zi Jie;Li Xiaoqian;Liu Yun;Ju Wen;Qi Kunming;Yan Zhiling;Li Zhenyu;Zeng Lingyu;Xu Kailin
免疫性血小板减少症（ITP）是一种以T免疫异常为特征的自身免疫性疾病。崩解素和金属蛋白酶（adam10）是蛋白酶家族的一员，已被证明具有调节T细胞增殖和效应功能。考虑到T细胞功能失调与ITP密切相关，ADAM10是否参与ITP的发病机制尚不清楚。本研究纳入54例活动性ITP患者、18例缓解期ITP患者和24例年龄和性别匹配的健康对照。分别从患者和对照组外周血单个核细胞（PBMCs）中分离RNA和血浆，采用实时荧光定量PCR检测ADAM10和组织金属蛋白酶3 (TIMP3) mRNA水平，ELISA检测血浆中FasL和淋巴细胞活化基因3 （LAG-3）可溶性水平。同时用流式细胞术检测T细胞活化情况。我们的研究结果显示，活动期ITP患者ADAM10的表达明显高于对照组，TIMP3的表达明显低于对照组，缓解期患者ADAM10和TIMP3均恢复到正常水平。与ADAM10的表达谱一致，活动性ITP患者血浆可溶性FasL和LAG-3水平升高，缓解期患者血浆可溶性FasL和LAG-3水平降至正常水平。此外，在活动性ITP患者中发现HLA-DR和CD69的高表达表明T细胞活化增加。综上所述，ADAM10的表达升高与ITP的发病和发展有关，靶向治疗可能是治疗ITP的新途径。
Immune thrombocytopenia (ITP) is an autoimmune disease, which is characterized by abnormal of T immunity. A disintegrin and metalloproteinase (ADAM) 10, a member of proteinase family, has been demonstrated to regulate T cell proliferation and effector function. Considering the closely association of dysregulation of T cell function with ITP, whether ADAM10 involves in the pathogenesis of ITP remains unclear. In this study, 54 active ITP patients, 18 ITP in remission and 24 age and gender matched healthy control were enrolled. Peripheral blood mononuclear cells (PBMCs) were isolated from patients and control for isolation of RNA and plasma which were used to measure mRNA level of ADAM10 and tissue inhibitor of metalloproteinase 3 (TIMP3) by quantitative real-time PCR and soluble level of FasL and lymphocyte activation gene-3 (LAG-3) in plasma by ELISA. Meanwhile, T cell activation was measured by flow cytometry. Our results showed significantly higher expression of ADAM10 and lower expression of TIMP3 in active ITP patients compared with control, which were all restored into normal level in remission patients. Consistent with the expression profile of ADAM10, increased soluble plasma level of FasL and LAG-3 were observed in active ITP patients and reduced to normal level in patients in remission. Furthermore, increased T cell activation as demonstrated by higher expression of HLA-DR and CD69 were found in active ITP patients. In conclusion, elevated expression of ADAM10 was associated with the pathogenesis and development of ITP and therapeutically targeting it might be a novel approach for the treatment of ITP.