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成人原发免疫性血小板减少症患者外周血Th9细胞的表达及其临床意义
郭慧军,叶辛,顾海慧,查占山,臧艳,钱宝华*
0
(第二军医大学长海医院输血科, 上海 200433
共同第一作者
*通信作者)
摘要:
目的 观察Th9细胞及IL-9在成人原发免疫性血小板减少症(primary immune thrombocytopenia,ITP)患者中的表达,探讨其在ITP发病过程中的作用。方法 纳入新诊断的成人ITP患者25例及年龄性别匹配的健康对照患者25例,利用流式细胞术检测研究对象外周血Th9细胞比例,实时荧光定量PCR检测IL-9、TGF-β、PU.1和IRF4的相对表达量,ELISA法检测IL-9的表达情况,血细胞计数仪进行血小板(PLT)计数。结果 与健康对照组相比,ITP患者外周血Th9细胞比例增高,且PLT≤30×109/L的患者Th9细胞比例高于PLT>30×109/L的患者(P<0.05)。ITP患者IL-9 mRNA及蛋白水平均增高,且PLT≤30×109/L的患者IL-9 mRNA及蛋白水平高于PLT>30×109/L的患者(P<0.05)。与健康对照组相比,ITP患者Th9细胞发育的主要调控因子TGF-β、PU.1和IRF4水平增高(P<0.05)。ITP患者Th9细胞比例和IL-9蛋白水平均与PLT负相关(r=-0.428 1,P=0.032 8; r=-0.537 5,P=0.005 6)。随访11例患者,发现经有效治疗后,Th9和IL-9与治疗前相比均呈下降趋势(P<0.05)。结论 Th9的异常活化可能参与了成人ITP疾病的发生与发展,这为进一步理解ITP的免疫学发病机制及选择免疫调节治疗潜在靶点提供了新的线索。
关键词:  原发免疫性血小板减少症  Th9细胞  白介素9
DOI:10.3724/SP.J.1008.2015.00155
投稿时间:2014-10-13修订日期:2015-01-31
基金项目:国家自然科学基金(81401358,81400152),第二军医大学长海医院“1255”学科建设计划(CH125531500),第二军医大学优秀硕士生苗子培育基金.
Th9 cells in peripheral blood of adult patients with primary immune thrombocytopenia and its clinical significance
GUO Hui-jun,YE Xin,GU Hai-hui,ZHA Zhan-shan,ZANG Yan,QIAN Bao-hua*
(Department of Blood Transfusion, Changhai Hospital, Second Military Medical University, Shanghai 200433, China
Co-first author.
*
Abstract:
Objective To observe Th9 cells and IL-9 level in adult patients with primary immune thrombocytopenia(ITP), and to discuss their potential roles in the pathogenesis of ITP. Methods A total of 25 newly diagnosed ITP patients and 25 sex- and age-matched healthy controls were enrolled in the present study. The percentage of Th9 cells in the peripheral blood samples of the two groups were detected by flow cytometry, expressions of IL-9, TGF-β, PU.1 and IRF4 mRNA were analyzed by real time-RCR, and IL-9 protein level was examined by ELISA. The platelet count was recorded by sysmex XE-2100. Results Compared with the healthy controls, the ratio of Th9 cells was significantly increased in ITP patients(P<0.05); and the ratio of Th9 cells in patients with PLT≤30×109/L was significantly higher than that in patients with PLT>30×109/L(P<0.05). IL-9 mRNA and protein expressions in ITP patients were significantly higher than those in the healthy controls, and those in patients with PLT≤30×109/L were also significantly higher than those with PLT>30×109/L(P<0.05). Compared with healthy controls, the mRNA expressions of IL-9, TGF-β, PU.1 and IRF4 were raised significantly in ITP patients(P<0.05). The ratio of Th9 cells and IL-9 protein level were negatively correlated with PLT in ITP patients(r=-0.428 1, P=0.032 8; r=-0.537 5, P=0.005 6, respectively). Furthermore, follow-up study of 11 ITP patients found that both Th9 cells and IL-9 protein levels took a declining tendency after effective treatment(P<0.05). Conclusion Abnormal activation of Th9/IL-9 may participate in the occurrence and development of ITP disease, which provides new clues for further understanding of ITP pathogenesis and selecting potential therapeutic targets in immune therapy of ITP.
Key words:  primary immune thrombocytopenia  Th9 cells  interleukin-9