慢性丙型肝炎患者外周血滤泡辅助性T淋巴细胞表面PD-1受体表达及意义研究
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摘要
目的探讨不同血清病毒载量的慢性丙型肝炎(CHC)患者外周血滤泡辅助性T淋巴细胞(Tfh)表面程序性死亡受体-1(PD-1)表达情况。方法根据血清HCV RNA水平不同,将180例CHC患者分为低病毒载量组76例,3 lg copies/ml≤血清HCV RNA <6 lg copies/ml和高病毒载量组104例,血清HCV RNA≥6 lgcopies/ml。比较两组外周血Tfh细胞百分比、Tfh细胞表面PD-1阳性率、外周血T、B淋巴细胞亚群、外周血CD4~+T淋巴细胞和CD8~+T淋巴细胞表面PD-1表达和血清白细胞介素21(IL-21)水平的差异。结果低病毒载量组和高病毒载量组血清HCV RNA水平分别为(4.5±1.2)lg copies/ml和(6.4±0.7)lg copies/ml,Tfh细胞表面PD-1阳性百分比分别为(26.2±2.2)%和(37.2±1.1)%,Tfh细胞百分比分别为(7.9±0.7)%和(5.1±0.4)%,血清IL-21水平分别为(46.8±1.3) ng/L和(21.7±1.1) ng/L,差异均有统计学意义(P<0.01);低病毒载量组和高病毒载量组外周血CD4~+T细胞百分比分别为(51.1±4.6)%和(37.6±4.4)%,CD8~+T细胞百分比分别为(24.0±3.1)%和(31.7±3.9)%,CD4~+T/CD8~+T细胞比值分别为(3.3±0.2)和(2.3±0.1),CD19~+B细胞百分比分别为(16.7±3.9)%和(11.8±3.2)%,差异具有统计学意义(P<0.01);低病毒载量组和高病毒载量组外周血CD4~+T细胞表面PD-1阳性率分别为(10.1±2.3)%和(2.4±0.6)%],CD8~+T细胞表面PD-1阳性率分别为(6.3±2.2)%和(1.0±0.3)%,差异也具有统计学意义(P<0.01)。结论不同血清病毒载量的CHC患者外周血Tfh和T淋巴细胞亚群以及血清白细胞介素21水平存在显著差异,进一步探讨它们对病情、抗病毒治疗应答和预后的关系,将具有十分重要的临床意义。
Objective To compare the difference of programmed cell death receptor-1(PD-1) receptor on peripheral blood follicular helper T lymphocyte(Tfh) surface in chronic hepatitis C(CHC) patients with low and high serum viral loads. Methods 180 patients with CHC were divided into two group,and 76 had serum HCV RNA level of less than 6 lg copies/ml and 104 had serum HCV RNA level of greater than 6 lg copies/ml. The percentage of PD-1 on peripheral blood Tfh cell surface,percentage of Tfh,peripheral blood T and B lymphocyte subsets and serum interleukin 21(IL-21) level were detected. Results In patients with low and high viral load groups,serum HCV RNA levels were(4.5±1.2) lg copies/ml and(6.4±0.7) lg copies/ml,the percentages of PD-1 on Tfh cell surface were(26.2±2.2)% and(37.2±1.1)%,the percentages of Tfh cells were(7.9±0.7)% and(5.1±0.4)%,and serum IL-21 levels were(46.8±1.3) ng/l and(21.7±1.1) ng/l,all significantly different between the two groups(P<0.05);the percentages of CD4~+T lymphocyte were(51.1±4.6)% and(37.6±4.4)%],the percentages of CD8~+T cell were(24.0±3.1)% and(31.7±3.9)%],the ratios of CD4~+T/CD8~+T cells were(3.3±0.2) and(2.3±0.1)],the percentage of CD19~+B cell were(16.7±3.9)%and(11.8±3.2)%,all significantly different between the two groups(P<0.05);the percentages of PD-1 on CD4~+T lymphocyte surface were(10.1 ±2.3)% and(2.4 ±0.6)% ],and the percentages of PD-1 on CD8 ~+T cell surface were(6.3±2.2)% and(1.0±0.3)%(both P<0.01). Conclusion There were significant differences between patients with low and high serum HCV RNA loads as respect to their peripheral blood Tfh and PD-1 expression,which might be important in evaluating the response to antiviral therapy and prognosis.
Objective To compare the difference of programmed cell death receptor-1(PD-1) receptor on peripheral blood follicular helper T lymphocyte(Tfh) surface in chronic hepatitis C(CHC) patients with low and high serum viral loads. Methods 180 patients with CHC were divided into two group,and 76 had serum HCV RNA level of less than 6 lg copies/ml and 104 had serum HCV RNA level of greater than 6 lg copies/ml. The percentage of PD-1 on peripheral blood Tfh cell surface,percentage of Tfh,peripheral blood T and B lymphocyte subsets and serum interleukin 21(IL-21) level were detected. Results In patients with low and high viral load groups,serum HCV RNA levels were(4.5±1.2) lg copies/ml and(6.4±0.7) lg copies/ml,the percentages of PD-1 on Tfh cell surface were(26.2±2.2)% and(37.2±1.1)%,the percentages of Tfh cells were(7.9±0.7)% and(5.1±0.4)%,and serum IL-21 levels were(46.8±1.3) ng/l and(21.7±1.1) ng/l,all significantly different between the two groups(P<0.05);the percentages of CD4~+T lymphocyte were(51.1±4.6)% and(37.6±4.4)%],the percentages of CD8~+T cell were(24.0±3.1)% and(31.7±3.9)%],the ratios of CD4~+T/CD8~+T cells were(3.3±0.2) and(2.3±0.1)],the percentage of CD19~+B cell were(16.7±3.9)%and(11.8±3.2)%,all significantly different between the two groups(P<0.05);the percentages of PD-1 on CD4~+T lymphocyte surface were(10.1 ±2.3)% and(2.4 ±0.6)% ],and the percentages of PD-1 on CD8 ~+T cell surface were(6.3±2.2)% and(1.0±0.3)%(both P<0.01). Conclusion There were significant differences between patients with low and high serum HCV RNA loads as respect to their peripheral blood Tfh and PD-1 expression,which might be important in evaluating the response to antiviral therapy and prognosis.
引文
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[18]Chowdhury A,Pm DRE,Tharp GK,et al.Decreased T follicular regulatory cell/T follicular helper cell(TFH)in simian Immunodeficiency virus-infected rhesus macaques may contribute to accumulation of TFH in chronic infection.J Immunol,2015,195(7):3237-3247.
[19]Wang C,Zhu H,Zhou Y,et al.Prognostic value of PD-L1 in breast cancer:a Meta-analysis.Breast J,2017,23(4):436-443.
[20]Morganstein DL,Lai Z,Spain L,et al.Thyroid abnormalities following the use of cytotoxic T-lymphocyte antigen-4 and programmed death receptor protein-1 inhibitors in the treatment of melanoma.Clin Endocrinol(Oxf),2017,86(4):614-620.
[2]Yamakage A,Ishikawa H.Generalized morphea-like scleroderma occurring in people exposed to organic solvents.Dermatologica,2009,165(3):186-193.
[3]Chen J,Zhang X,Luo H,et al.Changes in renal function indices in cirrhotic chronic hepatitis C patients treated with sofosbuvir-containing regimens.Oncotarget,2017,8(53):90916-90924.
[4]中华医学会肝病学分会和感染病学分会.《丙型肝炎防治指南》2015年更新版.实用肝脏病杂志,2016,19(4):ⅠⅩ-ⅩⅩⅤⅠ.
[5]Virlogeux V,Pradat P,Hartig-Lavie K,et al.Interferon-free direct-acting antiviral therapy decreases the rate of hepatocellular carcinoma recurrence in patients with chronic hepatitis Cand advanced fibrosis.J Hepatol,2017,66(1):745-751.
[6]Meissner EG,Kohli A,Higgins J,et al.Rapid changes in peripheral lymphocyte concentrations during interferon-free treatment of chronic hepatitis C virus infection.Hepatol Commun,2017,1(7):586-594.
[7]郭兆霞,王玉珍,苏少慧.慢性丙型肝炎患者心血管疾病研究进展.实用肝脏病杂志,2016,19(6):757-761.
[8]何涛君,杨来智,吴润香,等.102例慢性丙型肝炎患者血清免疫球蛋白和补体水平变化.实用肝脏病杂志,2015,18(5):538-539.
[9]Iom M,Sa DF,Aia NA,et al.Hemochromatosis gene polymorphism as a predictor of sustained virological response to antiviral treatment in Egyptian chronic hepatitis C patients.Euroasian J Hepatogastroenterol,2017,7(2):154-157.
[10]Vir P,Fendt L,Amaral K,et al.Prediction of sustained virological response to peginterferon-based therapy for chronic hepatitis C:regression analysis of a cohort from riogrande dosul,brazil.Euroasian J Hepatogastroenterol,2017,7(1):27-33.
[11]Mcgary CS,Deleage C,Harper J,et al.CTLA-4(+)PD-1(-)memory CD4(+)T cells critically contribute to viral persistence in antiretroviral therapy-suppressed,SIV-infected rhesus macaques.Immunity,2017,47(4):776-788.
[12]Miller SM,Miles B,Guo K,et al.Follicular regulatory T cells are highly permissive to R5-tropic HIV-1.J Virol,2017,91(17):11-17.
[13]Ayala VI,Deleage C,Trivett MT,et al.CXCR5 dependent entry of CD8 T cells into rhesus macaque B-cell follicles achieved through T-Cell engineering.J Virol,2017,91(11):1-8.
[14]Amiezer M,Phan TG.Disentangling Tfr cells from Treg cells and Tfh cells:how to untie the gordian knot.Eur J Immunol,2016,46(5):1101-1104.
[15]Kohler SL,Pham MN,Folkvord JM,et al.Germinal center Tfollicular helper cells are highly permissive to HIV-1 and alter their phenotype during virus replication.J Immunol,2016,196(6):2711-2722.
[16]Elela MA,Gawdat HI,Hegazy RA,et al.B cell activating factor and T-helper 17 cells:possible synergistic culprits in the pathogenesis of Alopecia Areata.Arch Dermatol Res,2016,308(2):115-121.
[17]Lang Q,Xu W,Li X,et al.Differential expression profile of immunological cytokines in local ovary in patients with polycystic ovarian syndrome:analysis by flow cytometry.Eur JObstet Gynecol Reprod Biol,2016,197(1):136-141.
[18]Chowdhury A,Pm DRE,Tharp GK,et al.Decreased T follicular regulatory cell/T follicular helper cell(TFH)in simian Immunodeficiency virus-infected rhesus macaques may contribute to accumulation of TFH in chronic infection.J Immunol,2015,195(7):3237-3247.
[19]Wang C,Zhu H,Zhou Y,et al.Prognostic value of PD-L1 in breast cancer:a Meta-analysis.Breast J,2017,23(4):436-443.
[20]Morganstein DL,Lai Z,Spain L,et al.Thyroid abnormalities following the use of cytotoxic T-lymphocyte antigen-4 and programmed death receptor protein-1 inhibitors in the treatment of melanoma.Clin Endocrinol(Oxf),2017,86(4):614-620.