慢性乙型肝炎患者外周血CD8^(+)CD25^(+)FoxP3^(+)调节性T细胞比例的变化及临床意义

The change and clinical significance of CD8^(+)CD25^(+)FoxP3^(+)regulatory T cell ratio in peripheral blood of patients with chronic hepatitis B

目的探讨外周血CD8^(+)CD25^(+)FoxP3^(+)调节性T细胞(Treg)比例在慢性乙型肝炎(CHB)患者中的变化及临床意义。方法选取2018年3-11月在滨海县第二人民医院传染科诊治的无症状乙型肝炎病毒(HBV)携带者28例为携带组,CHB患者28例为CHB组。同时选取28例年龄、性别匹配的健康体检者作为对照组。采用流式细胞仪分析外周血CD8^(+)CD25^(+)FoxP3^(+)Treg比例。比较各组肝功能相关指标、HBVDNA、外周血CD8^(+)CD25^(+)FoxP3^(+)Treg比例、外周血单个核细胞(PBMC)中叉头状转录因子P3(FoxP3)mRNA水平,以及血清白细胞介素(IL)-10、IL-35、转化生长因子(TGF)-β1水平。分析CHB患者外周血CD8^(+)CD25^(+)FoxP3^(+)Treg比例与肝功能相关指标、HBV-DNA、PBMC中FoxP3 mRNA水平,以及血清IL-10、TGF-β1、IL-35水平的相关性。结果与对照组、携带组相比,CHB组总胆红素(TBIL)、直接胆红素、丙氨酸氨基转移酶(ALT)和天门冬氨酸氨基转移酶水平均明显升高,差异有统计学意义(P<0.05)。与对照组相比,携带组、CHB组外周血CD8^(+)CD25^(+)FoxP3^(+)Treg比例、PBMC中FoxP3 mRNA水平及血清IL-10、TGF-β1、IL-35水平均明显升高,且CHB组均高于携带组,差异有统计学意义(P<0.05)。CHB患者外周血CD8^(+)CD25^(+)FoxP3^(+)Treg比例与PBMC中FoxP3 mRNA水平,血清IL-10、TGF-β1及IL-35水平均呈正相关(r=0.568、0.537、0.377、0.484,P<0.05);CHB患者外周血CD8^(+)CD25^(+)FoxP3^(+)Treg比例与TBIL、HBV-DNA、ALT水平呈正相关(r=0.536、0.570、0.443,P<0.05)。结论外周血CD8^(+)CD25^(+)FoxP3^(+)Treg比例升高可能在CHB患者疾病发展过程中发挥了重要作用。

Objective To investigate the change and clinical significance of CD8^(+)CD25^(+)FoxP3^(+)regulatory T cell(Treg)ratio in peripheral blood of patients with chronic hepatitis B(CHB).Methods Selected 28 a-symptomatic hepatitis B virus(HBV)carriers who were diagnosed and treated in the Department of Infectious Diseases,Binhai County Second People's Hospital from March to November 2018 as the carrier group,and 28 patients with CHB as the CHB group.At the same time,28 age and sex matched healthy subjects underwent physical examination were selected as the control group.The CD8^(+)CD25^(+)FoxP3^(+)Treg ratio in peripheral blood was analyzed by flow cytometry.Compared the liver function-related indicators,HBV-DNA,the periph-eral blood CD8^(+)CD25^(+)FoxP3^(+)Treg ratio,the forkhead transcription factor P3(FoxP3)mRNA level in pe-ripheral blood mononuclear cells(PBMC),and serum interleukin(IL)-10,IL-35,transforming growth factor(TGF)-β1 levels.Analyzed the correlation between the CD8^(+)CD25^(+)FoxP3^(+)Treg ratio in peripheral blood of CHB patients and liver function-related indicators,HBV-DNA,FoxP3 mRNA level in PBMC,and serum IL-10,TGF-β1,and IL-35 levels.Results Compared with the control group and carrier group,the total bilirubin(TBIL),direct bilirubin,alanine aminotransferase(ALT)and aspartate aminotransferase levels in the CHB group were significantly increased,the differences were statistically significant(P<0.05).Compared with the control group,the peripheral blood CD8^(+)CD25^(+)FoxP3^(+)Treg ratio,FoxP3 mRNA level in PBMC and serum IL-10,TGF-β1 and IL-35 levels in the carrier group and CHB group increased significantly,and those in the CHB group were higher than the carrier group,the differences were statistically significant(P<0.05).Pe-ripheral blood CD8^(+)CD25^(+)FoxP3^(+)Treg ratio in CHB patients correlated positively with FoxP3 mRNA level in PBMC,serum IL-10,TGF-β1 and IL-35 levels(r=0.568,0.537,0.377,0.484,P<0.05).Peripheral blood CD8^(+)CD25^(+)FoxP3^(+)Treg ratio in CHB patients correlated positively with the levels of TBIL,HBV-DNA and ALT(r=0.536,0.570,0.443,P<0.05).Conclusion The increased CD8^(+)CD25^(+)FoxP3^(+)Treg ratio in pe-ripheral blood of CHB patients may play an important role in the development of the disease.