CITP患者外周血Tfh/Tfr、Bcl-6/Blimp-1平衡与血小板自身抗体水平的相关性研究
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摘要
目的研究慢性特发性血小板减少性紫癜(CITP)患者外周血CD4+CXCR5+FoxP3-ICOS+T(Tfh)、CD4+CXCR5+FoxP3+ICOS+T(Tfr)细胞比例及转录因子Bcl-6/Blimp-1的变化,并探讨其与CITP患者血小板自身抗体阳性率之间的关系及临床意义。方法收集2016年2月-2018年3月确诊的CITP患者,随机选取30例作为病例组,同时选择30名健康人群作为对照组,分别采集病例组与对照组外周静脉血并分离单核细胞,采用流式细胞术(FCM)检测Tfh/Tfr细胞亚群的数量与比例,免疫组化法测定外周血单核细胞Bcl-6/Blimp-1蛋白表达水平,并分析Tfh/Tfr、Bcl-6/Blimp-1比值变化与血小板自身抗体阳性率之间的关系。结果与对照组比较,CITP组外周血Tfh细胞、Tfh/Tfr比值均升高,而Tfr细胞比例降低,差异均有统计学意义(P<0.05)。与对照组比较,CITP组外周血单核细胞转录因子Bcl-6表达和Bcl-6/Blimp-1比值升高,而转录因子Blimp-1表达降低,差异均有统计学意义(P<0.05)。相关性分析表明Tfh/Tfr、Bcl-6/Blimp-1比例变化与CITP患者外周血血小板自身抗体阳性率呈正相关(P<0.05),Tfr、Blimp-1的变化与血小板抗体阳性率呈负相关(P<0.05)。结论 Tfh/Tfr细胞及转录因子Bcl-6/Blimp-1平衡可能与CITP患者自身血小板抗体紊乱密切相关,该研究可为CITP的临床诊断与治疗提供新的靶点与思路,具有重要的临床意义。
Objective To study the peripheral blood CD4+CXCR5+FoxP3-ICOS+T(Tfh),CD4+CXCR5+FoxP3+ICOS+T(Tfr)subsets and related factor Bcl-6/Blimp-1 changes in patients with chronic idiopathic thrombocytopenic purpura(CITP),and explore their significances. Methods The rates of CD4+CXCR5+FoxP3-ICOS+T(Tfh),CD4+CXCR5+FoxP3+ICOS+T(Tfr)subsets of the peripheral blood from 30 patients with CITP and 30 healthy controls were analyzed by flow cytometry with immunofluorescent staining. The levels of the peripheral blood Bcl-6/Blimp-1 were detected by immunohistochemical method,the ratios of Bcl-6/Blimp-1 and Tfh/Tfr were analyzed,and the relationships between the Tfh/Tfr,Bcl-6/Blimp-1 ratios and PAIgG positive rates were studied. Results The numbers of peripheral blood Tfh were significantly increased in patients with CITP in comparison with those of healthy controls(P<0.05),but the Tfr subsets were lower than those of controls. The ratios of Tfh/Tfr and Bcl-6/Blimp-1 were significantly higher than those of controls(P<0.05),but the ratios of Tfr and Blimp-1 decreased compared with those of healthy controls(P<0.05). Besides,there were positive relations between the ratios of Tfh/Tfr,Bcl-6/Blimp-1 and PAIgG positive rates(P<0.05),but there were negative relationship between the ratio of Tfr,Blimp-1 and PAIgG positive rates(P<0.05). Conclusion The disorder of Tfh/Tfr subsets in peripheral blood of CITP and the changes of Tfh/Tfr and Bcl-6/Blimp-1 ratios might play an important role in the immune pathogenesis of CITP,and provide a new way for CITP clinical diagnose and treatment.
Objective To study the peripheral blood CD4+CXCR5+FoxP3-ICOS+T(Tfh),CD4+CXCR5+FoxP3+ICOS+T(Tfr)subsets and related factor Bcl-6/Blimp-1 changes in patients with chronic idiopathic thrombocytopenic purpura(CITP),and explore their significances. Methods The rates of CD4+CXCR5+FoxP3-ICOS+T(Tfh),CD4+CXCR5+FoxP3+ICOS+T(Tfr)subsets of the peripheral blood from 30 patients with CITP and 30 healthy controls were analyzed by flow cytometry with immunofluorescent staining. The levels of the peripheral blood Bcl-6/Blimp-1 were detected by immunohistochemical method,the ratios of Bcl-6/Blimp-1 and Tfh/Tfr were analyzed,and the relationships between the Tfh/Tfr,Bcl-6/Blimp-1 ratios and PAIgG positive rates were studied. Results The numbers of peripheral blood Tfh were significantly increased in patients with CITP in comparison with those of healthy controls(P<0.05),but the Tfr subsets were lower than those of controls. The ratios of Tfh/Tfr and Bcl-6/Blimp-1 were significantly higher than those of controls(P<0.05),but the ratios of Tfr and Blimp-1 decreased compared with those of healthy controls(P<0.05). Besides,there were positive relations between the ratios of Tfh/Tfr,Bcl-6/Blimp-1 and PAIgG positive rates(P<0.05),but there were negative relationship between the ratio of Tfr,Blimp-1 and PAIgG positive rates(P<0.05). Conclusion The disorder of Tfh/Tfr subsets in peripheral blood of CITP and the changes of Tfh/Tfr and Bcl-6/Blimp-1 ratios might play an important role in the immune pathogenesis of CITP,and provide a new way for CITP clinical diagnose and treatment.
引文
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[15]Mountz JD,Hsu HC,Ballesteros-Tato A.Dysregulation of Tfollicular helper cells in lupus[J].J Immunol,2019,202(6):1649-1658.2019-01-09
[2]张之南.血液病诊断及疗效标准[M].第2版.北京:北京科学出版社,1998.
[3]Audia S,Rossato M,Santegoets K,et al.Splenic TFH expansion participates in B-cell differentiation and antiplatelet-antibody production during immune thrombocytopenia[J].Blood,2014,124(18):2858-2866.
[4]Audia S,Rossato M,Trad M,et al.B cell depleting therapy regulates splenic and circulating T follicular helper cells in immune thrombocytopenia[J].Autoimmun,2017,77:89-95.
[5]Xie J,Cui D,Liu Y,et al.Changes in follicular helper T cells in idiopathic thrombocytopenic purpura patients[J].Int J Biol Sci,2015,11(2):220-229.
[6]Cui Y,Guan Y,Liu W,et al.The changes of circulating follicular regulatory T cells and follicular T helper cells in children immune thrombocytopenia[J].Zhonghua Xue Ye Xue Za Zhi,2014,35(11):980-984.
[7]Niu Q,Huang ZC,Wu XJ,et al.Enhanced IL-6/phosphorylated STAT3 signaling is related to the imbalance of circulating Tfollicular helper/T follicular regulatory cells in patients with rheumatoid arthritis[J].Arthritis Res Ther,2018,20(1):200-205.
[8]Wang X,Yang C,Xu F,et al.Imbalance of circulating Tfr/Tfh ratio in patients with rheumatoid arthritis[J].Clin Exp Med,2019,19(1):55-64.
[9]Xu B,Wang S,Zhou M,et al.The ratio of circulating follicular Thelper cell to follicular T regulatory cell is correlated with disease activity in systemic lupus erythematosus[J].Clin Immunol,2017,183:46-53.
[10]Wu CL,He JA,Gu DY,et al.Development of a Strategy Based on the Surface Plasmon Resonance Technology for Platelet Compatibility Testing[J].Clin Lab,2018,64(1):33-41.
[11]伍昌林,王前,郑磊,等.CITP患者外周血Breg与CD4+T细胞的相关性及临床意义[J].中国实验血液学杂志,2013,21(6):1517-1521.
[12]Chen Y,Yu D.TCF-1 at the Tfh and Th1 Divergence[J].Trends Immunol,2015,36(12):758-760.
[13]Donnarumma T,Young GR,Merkenschlager J,et al.Opposing development of cytotoxic and follicular helper CD4+T cells controlled by the TCF-1-Bcl-6 nexus[J].Cell Rep,2016,17(6):1571-1583.
[14]Yao X,Li C,Yang J,et al.Differences in frequency and regulation of T follicular helper cells between newly diagnosed and chronic pediatric immune thrombocytopenia[J].Blood Cells Mol Dis,2016,61:26-36.
[15]Mountz JD,Hsu HC,Ballesteros-Tato A.Dysregulation of Tfollicular helper cells in lupus[J].J Immunol,2019,202(6):1649-1658.2019-01-09