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TIPE2、Foxp3、CTLA-4 mRNA在慢性丙型肝炎患者外周血单个核细胞中的表达及临床意义
The mRNA expression of TIPE2, Foxp3, and CTLA-4 in peripheral blood mononucleated cells in patients with chronic hepatitis C and their clinical significance
文章发布日期:2019年01月07日  来源:  作者:孔丽,金萌,王卫真,等  点击次数:170次  下载次数:13次

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【摘要】:目的 探讨慢性丙型肝炎患者外周血单个核细胞(PBMC)中肿瘤坏死因子α诱导蛋白8样分子2(TIPE2)、调节性T淋巴细胞(Treg)功能分子叉头样转录因子3(Foxp3)和细胞毒性T淋巴细胞相关抗原4(CTLA-4)的表达及临床意义。方法 选取2012年5月-2016年12月在河北医科大学第三医院门诊及住院的未经抗病毒药物和免疫调节药物治疗的慢性丙型肝炎患者80例,另选取同期健康志愿者45例作为对照。应用实时荧光定量PCR法检测PBMC中TIPE2、Foxp3、CTLA-4 mRNA表达水平,并观察与肝脏血清生化指标及HCV RNA水平的相关性及TIPE2对Foxp3和CTLA-4的影响。计量资料两组间比较采用t检验;计数资料两组间比较采用χ2检验;相关分析采用Pearson相关性检验。结果 慢性丙型肝炎患者PBMC中TIPE2 mRNA表达较健康对照组显著降低(0.564±0.232 vs 0.704±0.165,t=3.569,P<0.001);Foxp3 mRNA和CTLA-4 mRNA表达较健康对照组明显升高(0.701±0.405 vs 0.527±0.184,t=2.725,P=0.007;0.638±0.211vs 0.448±0.134,t=5.449,P<0.001)。TIPE2 mRNA表达与ALT、AST、TBil水平及HCV RNA载量均呈负相关(r值分别为-0.368、-0.417、-0.416、-0.327,P值分别为0.001、<0.001、<0.001、0.003);Foxp3 mRNA表达与TBil水平呈负相关(r=-0.284,P=0.011);TIPE2 mRNA表达与Foxp3 mRNA、CTLA-4 mRNA表达均呈正相关(r值分别为0.461、0.257,P值分别为<0.001、0.021)。结论 慢性丙型肝炎患者存在TIPE2基因表达及Treg功能分子Foxp3、CTLA-4 mRNA表达数量和功能的异常,并且与肝细胞损伤程度和病毒复制有一定的关系,TIPE2基因可能通过正性调控Treg介导的免疫反应参与了慢性丙型肝炎的发病过程。
【Abstract】:Objective To investigate the mRNA expression of tumor necrosis factor-alpha-induced protein 8-like 2 (TIPE2), Foxp3 (a functional molecule for regulatory T cells), and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) in peripheral blood mononuclear cells (PBMCs) in patients with chronic hepatitis C (CHC) and their clinical significance. Methods A total of 80 CHC patients who were hospitalized in The Third Hospital of Hebei Medical University from May 2012 to December 2016 and did not receive antiviral drugs or immunoregulatory drugs were enrolled as CHC group, and 45 healthy volunteers were enrolled as controls. Quantitative real-time PCR was used to measure the mRNA expression of TIPE2, Foxp3, and CTLA-4 in PBMCs; the correlation between liver biochemical parameters and HCV RNA was observed, as well as the influence of TIPE2 on Foxp3 and CTLA-4. The t-test was used for comparison of continuous data between two groups, the chi-square test was used for comparison of categorical data between two groups, and Pearson correlation was used for correlation analysis. Results Compared with the healthy control group, the CHC group had a significant reduction in the mRNA expression of TIPE2 (0.564±0.232 vs 0.704±0.165, t=3.569, P<0.001) and significant increases in the mRNA expression of Foxp3 (0701±0.405 vs 0.527±0.184, t=2.725, P=0.007) and CTLA-4 (0.638±0.211 vs 0.448±0.134, t=5.449, P<0.001). The mRNA expression of TIPE2 was negatively correlated with serum alanine aminotransferase (r=-0.368, P=0.001), aspartate aminotransferase (r=-0.417, P<0.001), total bilirubin (r=-0.416, P<0.001), and HCV RNA load (r=-0.327, P=0.003) and was positively correlated with the mRNA expression of Foxp3 (r=0.461, P<0.001) and CTLA-4 (r=0.257, P=0.021). The mRNA expression of Foxp3 was negatively correlated with total bilirubin(r=-0.284,P=0.011). Conclusion CHC patients have abnormalities in the mRNA expression of TIPE2 and the mRNA expression and function of Foxp3 and CTLA-4, which is associated with the degree of hepatocellular injury and viral replication. The TIPE2 gene may be involved in the pathogenesis of CHC by positively regulating immune response mediated by regulatory T cells.
【关键字】:肝炎, 丙型, 慢性; 肿瘤坏死因子α诱导蛋白8样分子2; 叉头转录因子类; 细胞毒性T淋巴细胞相关抗原4; 外周血单个核细胞
【Key words】:hepatitis C, chronic; TIPE2; forkhead transcription factors; CTLA-4; peripheral blood mononuclear cell
【引证本文】:KONG L, JIN M, WANG WZ, et al. The mRNA expression of TIPE2, Foxp3, and CTLA-4 in peripheral blood mononucleated cells in patients with chronic hepatitis C and their clinical significance[J]. J Clin Hepatol, 2019, 35(2): 323-327. (in Chinese)
孔丽,金萌,王卫真,等. TIPE2、Foxp3、CTLA-4 mRNA在慢性丙型肝炎患者外周血单个核细胞中的表达及临床意义[J]. 临床肝胆病杂志, 2019, 35(2): 323-327.

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