免疫性血小板减少症患者CD19~+B细胞的表达及血清Breg在患者发病中的参与作用
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摘要
目的:研究免疫性血小板减少症(ITP)患者CD19~+B细胞的表达,分析血清Breg在ITP患者中的变化和影响。方法:选取2015年8月至2018年8月期间本院血液科收治的初次诊断为ITP患者68例(ITP组),选取同时段到我院体检中心的30例健康人(对照组),采用流式细胞术测定2组外周血淋巴细胞亚群CD19~+的表达率和外周血Breg细胞表达水平,对比治疗前、后ITP组与对照组之间的差别;采取RT-PCR检测各组IL-10mRNA、TGF-β1 mRNA水平,分析ITP患者外周血Breg细胞比值与IL-10 mRNA、TGF-β1 mRNA表达的相关性。结果:治疗前,ITP组CD19~+表达率显著高于对照组,两组间差异具有统计学意义。ITP组血清Breg细胞表达水平较对照组血清Breg细胞表达水平低;初诊ITP组IL-10 mRNA水平较对照组明显减低,治疗后其IL-10 mRNA水平较治疗前显著升高,差异具有统计学意义。此外,初诊ITP组TGF-β1 mRNA水平较对照组明显升高,治疗后其TGF-β1 mRNA水平较治疗前有所降低;外周血Breg细胞比值与IL-10 mRNA表达呈正相关(r=0.968,P <0.05),但外周血Breg细胞比值与TGF-β1 mRNA表达无相关性(r=0.502,P>0.05)。结论:ITP患者CD19~+细胞表达增强,临床中Breg细胞参与ITP发生发展,Breg细胞表达异常与ITP的发病有关。
Objective: To study the expression of CD19~+B cells in immune thrombocytopenia patients, and to analyze the involvement of serum Breg in the pathogenesis of ITP. Methods: A total of 68 ITP patients admitted in department of hematology in our hospital from August 2015 to August 2018 were selected and enrolled in ITP group. 30 healthy individuals who were admitted to physical examination center at the same time were selected and enrolled in control group. The expression of peripheral blood lymphocyte subsets CD19~+ and peripheral blood Breg cells were measured by flow cytometry. The difference between the ITP group and the control group was compared. The IL-10 mRNA and TGF-β1 mRNA levels were detected by RT-PCR. Correlations between the ratio of peripheral blood Breg cells and the expression of IL-10 mRNA and TGF-β1 mRNA in patients with immune thrombocytopenia, were analyzed. Results:Expression of CD19~+ in ITP group was significantly higher than that in control group. The difference between the two groups was statistically significant. Expression level of serum Breg cells in ITP group was lower than that in control group. IL-10 mRNA level in ITP group was significantly lower than that in control group. IL-10 mRNA level after treatment was significantly higher than that before treatment. In addition, TGF-β1 mRNA level in newly diagnosed ITP group was significantly higher than that in control group. After treatment, the TGF-β1 mRNA level was higher than that before treatment. The ratio of peripheral blood Breg cells positively correlated with IL-10 mRNA expression(r=0.968,P<0.05), however, there was no correlation between peripheral blood Breg cell ratio and TGF-β1 mRNA expression(r=0.502, P>0.05). Conclusion: Expression of CD19~+ cells in ITP patients is increased. Breg cells may participate in the genesis of immune thrombocytopenia. The abnormal expression of Breg cells relates with the pathogenesis of immune thrombocytopenia.
Objective: To study the expression of CD19~+B cells in immune thrombocytopenia patients, and to analyze the involvement of serum Breg in the pathogenesis of ITP. Methods: A total of 68 ITP patients admitted in department of hematology in our hospital from August 2015 to August 2018 were selected and enrolled in ITP group. 30 healthy individuals who were admitted to physical examination center at the same time were selected and enrolled in control group. The expression of peripheral blood lymphocyte subsets CD19~+ and peripheral blood Breg cells were measured by flow cytometry. The difference between the ITP group and the control group was compared. The IL-10 mRNA and TGF-β1 mRNA levels were detected by RT-PCR. Correlations between the ratio of peripheral blood Breg cells and the expression of IL-10 mRNA and TGF-β1 mRNA in patients with immune thrombocytopenia, were analyzed. Results:Expression of CD19~+ in ITP group was significantly higher than that in control group. The difference between the two groups was statistically significant. Expression level of serum Breg cells in ITP group was lower than that in control group. IL-10 mRNA level in ITP group was significantly lower than that in control group. IL-10 mRNA level after treatment was significantly higher than that before treatment. In addition, TGF-β1 mRNA level in newly diagnosed ITP group was significantly higher than that in control group. After treatment, the TGF-β1 mRNA level was higher than that before treatment. The ratio of peripheral blood Breg cells positively correlated with IL-10 mRNA expression(r=0.968,P<0.05), however, there was no correlation between peripheral blood Breg cell ratio and TGF-β1 mRNA expression(r=0.502, P>0.05). Conclusion: Expression of CD19~+ cells in ITP patients is increased. Breg cells may participate in the genesis of immune thrombocytopenia. The abnormal expression of Breg cells relates with the pathogenesis of immune thrombocytopenia.
引文
1中华医学会血液学分会血栓与止血学组.成人原发免疫性血小板减少症诊断与治疗中国专家共识(2016年版).中华血液学杂志,2016;37(2):89-93.
2阮毅燕,陈瑜毅,唐文珏,等.特发性血小板减少性紫癜患儿细胞免疫功能变化及临床意义.医学研究杂志,2017;46(2):43-45.
3 Yu S,Liu C,Li L,et al.Inactivation of Notch signaling reverses the Th17/Treg imbalance in cells from patients with immune thrombocytopenia.Lab Invest,2015;95(2):157-167.
4苏敏利,韩艳秋.原发免疫性血小板减少症的研究进展.世界最新医学信息文摘,2018;18(72):319-320+322.
5马静瑶,陈振萍,吴润晖,等.血小板特异性抗体与ITP发病、临床特点、治疗及预后效果的关系.中国实验血液学杂志,2014;22(06):1771-1774.
6 Adams G,Graebner L,Sayed A,et al.Cytokine fluctuations in immune thrombocytopenia(ITP)over time;insights into the pathogenesis and evolution of the disease.Blood,2016;128(22):2549-2551.
7张之南.血液病诊断及疗效标准3版.北京:科学出版社,2008:172-175.
8王明镜,胡晓梅,邓中阳,等.免疫性血小板减少症的免疫机制研究进展.临床血液学杂志,2017;30(5):725-728.
9 Qu W,Tang YJ,Shao ZH.Regulatory B cells decreased in patients with immune thrombocytopenia.Blood,2015;126(23):4627-4628.
10 Takahashi N,Saitoh T,Gotoh N,et al.The cytokine polymorphisms affecting Th1/Th2 increase the susceptibility to,and severity of,chronic ITP.BMC Immunol,2017;18(1):26.
11王颖超,刘满菊,朱桂英,等.Th17/Treg细胞比例失衡在儿童原发性免疫性血小板减少症中的意义.中国当代儿科杂志,2016;18(3):238-242.
12朱玲玲,张彦,刘开蕾,等.原发性免疫性血小板减少症患者治疗前后T淋巴细胞亚群变化的临床意义.中国医药科学,2018;8(17):205-207.
13章大谦,宁静,吴广胜.大剂量地塞米松与人免疫球蛋白联合治疗对成人免疫性血小板减少症患者T细胞免疫功能的影响.广东医学,2018;39(17):2667-2671.
14王明镜,许勇钢,丁晓庆,等.免疫性血小板减少症患者的细胞免疫功能研究.中华临床医师杂志(电子版),2018;12(2):65-69.
15张春梅.免疫性血小板减少症患者淋巴细胞亚群表达及其与血小板抗体、临床特征的相关性研究.中国煤炭工业医学杂志,2012;15(10):1524-1526.
16 Tang Y,Qu W,Wang Y,et al.Quantity and function of regulatory B cells of the patients with immune thrombocytopenia.Zhonghua Yi Xue Za Zhi,2015;95(20):1599-1601.
17李鑫,王芳,丁凯阳,等.调节性B细胞在免疫性血小板减少症发病过程中的意义.中国实验血液学杂志,2014;22(2):403-406.
18郭莹,瞿文,王一浩,等.共刺激信号分子对免疫性血小板减少症患者B淋巴细胞免疫功能的影响.中国实验血液学杂志,2016;24(04):1110-1115.
19王春美,罗源,王颖超,等.新诊断免疫性血小板减少症患儿外周血调节性B淋巴细胞的表达及意义.中华实用儿科临床杂志,2016;31(3):209-211.
2阮毅燕,陈瑜毅,唐文珏,等.特发性血小板减少性紫癜患儿细胞免疫功能变化及临床意义.医学研究杂志,2017;46(2):43-45.
3 Yu S,Liu C,Li L,et al.Inactivation of Notch signaling reverses the Th17/Treg imbalance in cells from patients with immune thrombocytopenia.Lab Invest,2015;95(2):157-167.
4苏敏利,韩艳秋.原发免疫性血小板减少症的研究进展.世界最新医学信息文摘,2018;18(72):319-320+322.
5马静瑶,陈振萍,吴润晖,等.血小板特异性抗体与ITP发病、临床特点、治疗及预后效果的关系.中国实验血液学杂志,2014;22(06):1771-1774.
6 Adams G,Graebner L,Sayed A,et al.Cytokine fluctuations in immune thrombocytopenia(ITP)over time;insights into the pathogenesis and evolution of the disease.Blood,2016;128(22):2549-2551.
7张之南.血液病诊断及疗效标准3版.北京:科学出版社,2008:172-175.
8王明镜,胡晓梅,邓中阳,等.免疫性血小板减少症的免疫机制研究进展.临床血液学杂志,2017;30(5):725-728.
9 Qu W,Tang YJ,Shao ZH.Regulatory B cells decreased in patients with immune thrombocytopenia.Blood,2015;126(23):4627-4628.
10 Takahashi N,Saitoh T,Gotoh N,et al.The cytokine polymorphisms affecting Th1/Th2 increase the susceptibility to,and severity of,chronic ITP.BMC Immunol,2017;18(1):26.
11王颖超,刘满菊,朱桂英,等.Th17/Treg细胞比例失衡在儿童原发性免疫性血小板减少症中的意义.中国当代儿科杂志,2016;18(3):238-242.
12朱玲玲,张彦,刘开蕾,等.原发性免疫性血小板减少症患者治疗前后T淋巴细胞亚群变化的临床意义.中国医药科学,2018;8(17):205-207.
13章大谦,宁静,吴广胜.大剂量地塞米松与人免疫球蛋白联合治疗对成人免疫性血小板减少症患者T细胞免疫功能的影响.广东医学,2018;39(17):2667-2671.
14王明镜,许勇钢,丁晓庆,等.免疫性血小板减少症患者的细胞免疫功能研究.中华临床医师杂志(电子版),2018;12(2):65-69.
15张春梅.免疫性血小板减少症患者淋巴细胞亚群表达及其与血小板抗体、临床特征的相关性研究.中国煤炭工业医学杂志,2012;15(10):1524-1526.
16 Tang Y,Qu W,Wang Y,et al.Quantity and function of regulatory B cells of the patients with immune thrombocytopenia.Zhonghua Yi Xue Za Zhi,2015;95(20):1599-1601.
17李鑫,王芳,丁凯阳,等.调节性B细胞在免疫性血小板减少症发病过程中的意义.中国实验血液学杂志,2014;22(2):403-406.
18郭莹,瞿文,王一浩,等.共刺激信号分子对免疫性血小板减少症患者B淋巴细胞免疫功能的影响.中国实验血液学杂志,2016;24(04):1110-1115.
19王春美,罗源,王颖超,等.新诊断免疫性血小板减少症患儿外周血调节性B淋巴细胞的表达及意义.中华实用儿科临床杂志,2016;31(3):209-211.