乙型肝炎患者外周血T细胞亚群、IL-6及IL-8水平的表达及临床意义

目的:探讨乙型肝炎患者外周血T细胞亚群、白细胞介素-6(IL-6)及白细胞介素-8(IL-8)水平的表达及临床意义。方法:选取2015年1月-2017年12月期间我院收治的乙型肝炎患者240例为研究对象。其中急性乙型肝炎患者55例(急性组),慢性乙型肝炎患者185例,并根据临床症状严重程度分为慢性轻度组65例、慢性中度组61例、慢性重度组59例。将乙型肝炎患者HBV-DNA载量103copy/m L作为HBV-DNA阳性组(n=158),HBV-DNA载量≤103copy/m L作为HBV-DNA阴性组(n=82)。另选取同期于我院行健康体检的志愿者50例为对照组。比较各组研究对象CD3+、CD4+、CD8+、CD4+/CD8+、IL-6、IL-8水平,比较HBV-DNA阳性组、HBV-DNA阴性组患者血清丙氨酸转氨酶(ALT)、总胆红素(TB)以及白蛋白(ALB)水平。采用Pearson相关性分析乙型肝炎患者血清IL-6、IL-8与肝功能指标的相关性。结果:急性组、慢性轻度组、慢性中度组、慢性重度组的CD3+、CD4+、CD4+/CD8+水平均低于对照组,CD8+、IL-6、IL-8均高于对照组(P0.05)。HBV-DNA阳性组与HBV-DNA阴性组CD3+、CD4+、CD8+、CD4+/CD8+、IL-6、IL-8、ALT、TB以及ALB比较差异无统计学意义(P0.05)。Pearson相关性分析显示,乙型肝炎患者血清中IL-6、IL-8均与ALT、TB水平呈正相关,与ALB水平呈负相关(P0.05)。结论:乙型肝炎患者CD3+、CD4+和CD4+/CD8+显著降低,CD8+、IL-6和IL-8显著升高,且血清中IL-6、IL-8水平可反映乙型肝炎患者肝细胞损害程度及病情严重程度。     

乙型肝炎患者凝血功能与胱抑素C 联合检测的临床意义

目的:探讨乙型肝炎患者凝血功能与血清胱抑素C联合检测的临床诊断价值。方法:收集260例乙型肝炎患者为实验组及健康者70例为对照组,采用全自动凝血分析仪进行活化部分凝血酶时间(APTT)、凝血酶原时间(PT)、纤维蛋白原(FIB)的测定,采用全自动生化分析仪进行血清胱抑素C、丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、血清γ谷氨酰转肽酶(GGT)的检测。结果:除急性肝炎组外,其他各组乙型肝炎患者的APTT、PT值均高于对照组(P<0.05)。重型肝炎和肝炎肝硬化组FIB值均低于对照组(P<0.05);对于血清胱抑素C水平,除急性肝炎组外,其他各组值均明显高于健康对照组(P<0.05),且肝炎肝硬化组依次高于重型肝炎组和慢性肝炎组。各实验组ALT和AST水平均明显高于对照组(P<0.05),而对于GGT水平,重型肝炎组和肝炎肝硬化组明显高于对照组(P<0.05)。结论:联合检测APTT、PT、FIB凝血功能指标与血清胱抑素C水平,对临床判断乙型肝炎患者病变程度及预后具有重要意义。     

慢性乙型肝炎患者血清白介素17A和胆碱酯酶的表达及临床意义

目的:检测慢性乙型肝炎(CHB)患者血清白介素17A(IL-17A)、胆碱酯酶(CHE)水平,并分析其临床意义。方法:选取2018年1月到2019年3月期间在重庆三峡中心医院接受治疗的CHB患者84例,根据病情严重程度将所有患者分为轻度组30例、中度组28例、重度组26例,另选取同期在重庆三峡中心医院进行体检的健康志愿者50例作为对照组。比较各组的凝血四项指标[纤维蛋白原(FIB)、凝血酶原时间(PT)、凝血活酶时间(APTT)、凝血酶时间(TT)]、肝功能指标[谷丙转氨酶(ALT)、谷草转氨酶(AST)]、IL-17A、CHE水平,采用Pearson相关分析CHB患者血清IL-17A、CHE与凝血四项、ALT、AST的相关性。结果:重度组、中度组、轻度组、对照组的FIB、CHE水平逐渐升高,PT、APTT、TT、ALT、AST、IL-17A水平逐渐降低,两两比较均有统计学差异(P0.05),IL-17A与FIB、CHE呈负相关,与PT、APTT、TT、ALT、AST呈正相关(P0.05);CHE与FIB呈正相关,与PT、APTT、TT、ALT、AST呈负相关(P0.05)。结论:CHB患者血清中IL-17A、CHE水平与患者的肝功能和凝血功能密切相关,联合检测IL-17A和CHE有助于患者的病情评估以及预后判断。     

白介素-32在HBV感染者的变化及其临床意义

目的:探讨乙型肝炎病毒(HBV)感染者血清中白介素-32(IL-32)水平的变化及其临床意义。方法:对100例HBV感染者和30例健康者检测外周血清白细胞介素-32(IL-32)的含量,比较IL-32水平变化的规律,并分析其与临床疾病谱和HBV复制水平的关系。结果:(1)急性乙型肝炎、中度慢性乙型肝炎、重度慢性乙型肝炎患者血清IL-32水平与对照组有显著性差异(P<0.001);轻度慢性乙型肝炎患者血清IL-32水平高于健康对照组,但无统计学意义(P>0.05);急性乙型肝炎、中、重度慢性乙型肝炎患者血清IL-32水平均显著高于轻度慢性乙型肝炎组,且有统计学意义(P<0.001);急性乙型肝炎、重度慢性乙型肝炎患者血清IL-32水平均高于中度慢性乙型肝炎组,有统计学意义(P<0.001);急性乙型肝炎、重度慢性乙型肝炎组之间无明显差异(P>0.05)。(2)HBV感染者HBV-DNA阳性组IL-32水平较阴性组为高,但无差异;高、中、低病毒载量组之间血清IL-32水平也无差异(P>0.05)。(3)慢性乙型肝炎患者不同ALT水平组血清IL-32水平均高于对照组(P<0.05);且低、中、高ALT水平组之间与I...     

老年支气管哮喘患者血清25-羟维生素D3浓度与免疫功能及肺功能的相关性研究

目的:研究老年支气管哮喘患者血清25-羟维生素D3[25-(OH)D3]浓度与免疫功能及肺功能的关系。方法:选取2016年1月至2017年12月我院收治的老年支气管哮喘患者96例作为研究组,根据肺功能检查结果分为轻度哮喘组(n=30)、中度哮喘组(n=38)和重度哮喘组(n=28),另选取同期在我院进行体检的健康老年人40例作为对照组。比较各组血清25-(OH)D3浓度、第一秒最大呼气量占用力肺活量百分比(FEV1/FVC)、FEV1占预计值百分比(FEV1%pred)、CD4~+、CD8~+、CD4~+/CD8~+以及血清免疫球蛋白A(IgA)、免疫球蛋白M(IgM)、免疫球蛋白G(IgG)水平,并分析血清25-(OH)D3与免疫功能指标及肺功能指标的相关性。结果:研究组血清25-(OH)D3浓度、FEV1%pred水平均低于对照组(P0.05),两组FEV1/FVC水平比较差异无统计学意义(P0.05)。研究组CD4~+、CD4~+/CD8~+、血清IgA、IgM、IgG水平均低于对照组,CD8~+水平高于对照组(P0.05)。重度哮喘组血清25-(OH)D3、IgA、IgM、IgG水平、FEV1%pred、CD4~+、CD4~+/CD8~+均低于中度哮喘组和轻度哮喘组,中度哮喘组又低于轻度哮喘组(P0.05),重度哮喘组CD8~+水平高于中度哮喘组和轻度哮喘组,中度哮喘组又高于轻度哮喘组(P0.05)。经Pearson相关性分析可得:老年支气管哮喘患者血清25-(OH)D3与FEV1%pred、CD4~+、CD4~+/CD8~+、IgA、IgM、IgG均呈正相关(P0.05),与CD8~+呈负相关(P0.05)。结论:老年支气管哮喘患者的血清25-(OH)D3浓度显著降低,且与肺功能和免疫功能相关,25-(OH)D3浓度的检测可用于评估患者病情严重程度。     

双歧杆菌四联活菌片对乙肝相关慢加急性肝衰竭合并感染患者肠道菌群及免疫功能的影响

目的分析双歧杆菌四联活菌片对乙肝相关慢加急性肝衰竭(HBV-ACLF)合并感染患者肠道菌群及免疫功能的影响,为该病的治疗提供参考。方法选择2017年12月至2018年12月我院收治的106例HBV-ACLF合并感染患者,采用随机数字表法将其分为对照组(n=53)与研究组(n=53)。对照组患者采用常规治疗,研究组患者在对照组基础上口服双歧杆菌四联活菌片,两组患者均治疗1个月。比较两组患者治疗总有效率及肠道菌群(双歧杆菌、肠球菌、乳杆菌、肠杆菌)、免疫功能(CD4~+细胞、CD8~+细胞、CD4~+/CD8~+)、肝功能[丙氨酸氨基转移酶(ALT)、天冬氨酸转氨酶(AST)]情况。结果研究组患者治疗总有效率显著高于对照组(90.57%vs 73.58%,χ~2=5.194,P=0.023)。治疗前,两组患者肠道双歧杆菌、肠球菌、乳杆菌、肠杆菌数量及CD4~+细胞、CD8~+细胞、CD4~+/CD8~+、AST、ALT水平差异无统计学意义(均P0.05)。治疗后,对照组患者肠道双歧杆菌、肠球菌、乳杆菌、肠杆菌数量较治疗前差异无统计学意义(均P0.05),而研究组患者肠道乳杆菌、双歧杆菌数量较治疗前显著升高,肠杆菌、肠球菌数量较治疗前显著下降(均P0.05)。治疗后两组患者CD4~+细胞、CD4~+/CD8~+水平较治疗前显著升高,CD8~+细胞、AST、ALT水平较治疗前显著下降(均P0.05)。治疗后研究组患者CD4~+细胞、CD4~+/CD8~+水平较对照组显著升高,CD8~+细胞、AST、ALT水平较对照组显著下降(均P0.05)。结论双歧杆菌四联活菌片治疗HBV-ACLF合并感染患者的临床疗效较好,能够调节患者肠道菌群,改善患者免疫功能及肝功能,值得临床推广。     

乙型肝炎患者体液免疫功能、肝纤维化指标及α1-MG、TGF-β1水平分析

目的:探讨乙型肝炎患者体液免疫功能、肝纤维化程度及血清中α1-MG、TGF-β1水平的变化。方法:选取2016年1月~2018年10月我院收治的轻度乙型肝炎患者60例为轻度组,重度乙型肝炎患者60例为重度组及同期来我院体检的健康志愿者60例为对照组。检测并比较三组患者血清中补体C3、补体C4、肝纤维化指标及α1-微球蛋白(α1-MG)、转化生长因子-β1(TGF-β1)水平。结果:乙型肝炎患者血清中补体C3及补体C4水平明显低于对照组;重度组患者血清中补体C3及补体C4水平明显低于轻度组患者(P<0.05)。乙型肝炎患者血清中各肝纤维化指标水平明显高于对照组;重度组患者血清中各肝纤维化指标水平明显高于轻度组患者(P<0.05)。乙型肝炎患者血清中α1-MG水平明显低于对照组,TGF-β1水平明显高于对照组;重度组患者血清中α1-MG水平明显低于轻度组,TGF-β1水平明显高于轻度组(P<0.05)。结论:乙型肝炎病毒感染可导致患者免疫功能水平下降,肝脏纤维化及细胞因子水平紊乱,且上述指标水平的变化与疾病进展程度密切相关,临床治疗时需加强对上述指标的监测。     

CD4+CD25+调节性T细胞在自身免疫性肝炎发病中的作用

目的:比较自身免疫性肝炎(autoimmune hepatitis,AIH)患者与健康对照者(healthy controls,HCs)外周血CD4+CD25+调节性T细胞(CD4+CD25+Tregs)数量、免疫抑制功能的变化,探讨CD4+CD25+Tregs参与AIH发病的可能机制.方法:采用流式细胞仪检测8例AIH患者及15例健康对照组的外周血CD4+CD25+Tregs数量的百分比及绝时数量;采用共同培养方法检测AIH患者外周血CD4+CD25+Tregs的免疫抑制功能的变化;实时荧光定量聚合酶链反应(RT-FQ-PCR)检删AIH患者外周血CD4+CD25+Tregs中FoxP3mRNA的表达.结果:AIH患者外周血CD4+CD25+Tregs数量明显低于HCs(p<0.01);混合淋巴细胞共同培养结果显示,AIH患者外周血CD4+CD25+Tregs抑制功能明显低于HCs组(p<0.01);AIH患者外周血CD4+CD25+Tregs的FoxP3 mRNA相对表达量显著降低,与HCs组比较有显著性差异(p<0.01).结论:CD4+CD25+Tregs细胞的数量的减少和Foxp3表达的降低所造成的CD4+CD25+Tregs细胞免疫抑制功能受损可能是AIH发病的一个因素.     

恩替卡韦联合异甘草酸镁注射液对慢性乙型肝炎患者血清IL-2、IL-10、IL-17、MIF及外周血T细胞亚群水平的影响

目的:探讨恩替卡韦联合异甘草酸镁注射液对慢性乙型肝炎患者血清白细胞介素-2(IL-2)、白细胞介素-10(IL-10)、白细胞介素-17(IL-17)、巨噬细胞移动抑制因子(MIF)及外周血T细胞亚群水平的影响。方法:选择我院2015年6月~2016年12月收治的92例慢性乙型肝炎患者,并按不同治疗方式分为对照组与研究组,每组46例。对照组采用恩替卡韦治疗,研究组基于对照组加以异甘草酸镁注射液治疗。比较两组的临床疗效,治疗前后血清IL-2、IL-10、IL-17、MIF、谷丙转氨酶(ALT),谷草转氨酶(AST),总胆红素(TbiL)水平,外周血CD3~+、CD4~+、CD8~+、CD4~+/CD8~+的变化及不良反应的发生情况。结果:治疗后,研究组总有效率高于对照组[93.47%vs.71.74%],差异有统计学意义(P0.05);两组血清IL-2水平及外周血CD3~+、CD4~+、CD4~+/CD8~+水平均较治疗前显著上升,且研究组以上指标均明显高于对照组,两组血清IL-10、IL-17、MIF、ALT、AST、TbiL水平及外周血CD8~+水平均较治疗前显著下降,且研究组以上指标均明显低于对照组,差异均有统计学意义(P0.05)。两组不良反应发生率比较差异无统计学意义(P0.05)。结论:恩替卡韦联合异甘草酸镁注射液对慢性乙型肝炎患者的效果优于单用恩替卡韦,可能与其显著升高血清IL-2、外周血CD3~+、CD4~+、CD4~+/CD8~+水平及降低血清IL-10、IL-17、MIF和外周血CD8~+水平有关。     

CD4~+T、CD8~+T、CD4~+/CD8~+与慢性乙肝不同中医体质存在相关性

探讨外周血CD4~+、CD8~+T水平与慢性乙型肝炎不同中医体质的关系。选取2016年2月至2017年3月在我院治疗的慢性乙型感染患者143例,其中平和质35例、气虚质40例、阴虚质21例、湿热质20例,气郁质16例、其他11例,采用流式细胞仪检测外周血T淋巴细胞亚群。不同中医体质患者性别、年龄、病程及HBV-DNA含量比较差异无统计学意义(p0.05);平和质患者AST为342.21(142.42,513.46)U/L,明显低于其他患者(p0.05);气虚质患者AST为512.40(322.81,726.50)U/L,明显高于其他患者(p0.05);气郁质及其他体质患者ALT分别为381.64(210.41,501.72)U/L和370.43(200.41,470.63)U/L,明显高于平和质、气虚质、阴虚质和湿热质患者(p0.05);平和质和气虚质患者外周血CD4~+T细胞分别为(39.10±2.01)%和(39.10±2.01)%,明显低于阴虚质、湿热质、气郁质及其他体质患者(p0.05);气郁质及其他体质患者CD8~+T细胞分别为(25.43±1.33)%和(25.24±1.31)%,明显低于平和质、气虚质、阴虚质和湿热质患者(p0.05);阴虚质、气郁质及其他体质患者分别为(1.71±0.09)、(1.75±0.08)和(1.78±0.09),明显高于平和质、气虚质和湿热质患者(p0.05)。慢性乙肝不同中医体质与CD4~+T、CD8~+T和以及肝功能有密切关系。关键词     

干扰素对慢性乙肝患者CD25表达及PBMC内HBV-DNA的作用

目的 探讨干扰素对慢性乙肝患者CD25的诱导及其对PBMC内的HBV-DNA的抗病毒作用.方法 将94例慢性乙肝患者分为A(48例)、B(46例)两组,分别采用IFN-α2b和常规治疗2个疗程.应用生物素-链霉亲和素(biotin-streptavidin,BSA)法检测治疗前后的及PHA体外诱导后的患者PBMC的CD...     

Altered mRNA levels of MOV10, A3G,and IFN-α in patients with chronic hepatitis B

To explore the relationship of the MOV10, A3G, and IFN-α mRNA levels with chronic hepatitis B virus (HBV) infection, Blood samples from 96 patients with chronic hepatitis B (CHB) and 21 healthy individuals as control were collected. HBV DNA load and aminotransferase in the serum were tested using real time PCR and velocity methods, respectively. The MOV10, A3G, and IFN-α mRNA levels in the peripheral blood mononuclear cells (PBMC) were examined through qRT-PCR. The MOV10, A3G, and IFN-α mRNA levels in CHB group was significantly lower than those in the control group (P<0.01, P<0.05, P<0.01, respectively). The A3G mRNA level in the high-HBV DNA load group was lower than that in the low-HBV DNA load group (P<0.05). However, no statistical difference was found in the MOV10 and IFN-α mRNA levels between the two HBV DNA load groups. Furthermore, the MOV10 mRNA level showed positive correlation with IFN-α in the control group. These results indicated that the expression of the innate immune factors MOV10, A3G, and IFN-α is affected by chronic HBV infection.     

HBV感染者外周血PBMC中TLR4 mRNA与病毒载量的相关性研究

目的探讨乙型肝炎病毒感染者外周血PBMC中TLR mRNA与乙肝病毒复制的相关性。方法采用逆转录PCR检测外周血单个核细胞（PBMC）中TLR4 mRNA的含量,实时荧光定量Real Time PCR的方法检测HBV DNA,进行相关性分析。结果不同病毒载量组（〈1×103copies/μg DNA,1×103copies/μg DNA〈且〈1×105copies/μg DNA,〉1×105copies/μg DNA）TLR4 mRNA水平差异具有显著性（P〈0.01）,HBV病毒载量的对数值与TLR4 mRNA的含量存在负相关（r=-0.537,P〈0.01）。TLR4 mRNA的相对表达量与患者的ALT、AST呈正相关（r=0.608、r=0.659,P〈0.01）。结论HBV在患者体内复制活跃、病毒载量增高与外周血单个核细胞TLR4mRNA的表达下调有关。     

Detection of Hepatitis B Virus (HBV) Genomes and HBV Drug Resistant Variants by Deep Sequencing Analysis of HBV Genomes in Immune Cell Subsets of HBV Mono-Infected and/or Human Immunodeficiency Virus Type-1 (HIV-1) and HBV Co-Infected Individuals

The hepatitis B virus (HBV) and the human immunodeficiency virus type 1 (HIV-1) can infect cells of the lymphatic system. It is unknown whether HIV-1 co-infection impacts infection of peripheral blood mononuclear cell (PBMC) subsets by the HBV. Aims To compare the detection of HBV genomes and HBV sequences in unsorted PBMCs and subsets (i.e., CD4+ T, CD8+ T, CD14+ monocytes, CD19+ B, CD56+ NK cells) in HBV mono-infected vs. HBV/HIV-1 co-infected individuals. Methods Total PBMC and subsets isolated from 14 HBV mono-infected (4/14 before and after anti-HBV therapy) and 6 HBV/HIV-1 co-infected individuals (5/6 consistently on dual active anti-HBV/HIV therapy) were tested for HBV genomes, including replication indicative HBV covalently closed circular (ccc)-DNA, by nested PCR/nucleic hybridization and/or quantitative PCR. In CD4+, and/or CD56+ subsets from two HBV monoinfected cases, the HBV polymerase/overlapping surface region was analyzed by next generation sequencing. Results All analyzed whole PBMC from HBV monoinfected and HBV/HIV coinfected individuals were HBV genome positive. Similarly, HBV DNA was detected in all target PBMC subsets regardless of antiviral therapy, but was absent from the CD4+ T cell subset from all HBV/HIV-1 positive cases (P<0.04). In the CD4+ and CD56+ subset of 2 HBV monoinfected cases on tenofovir therapy, mutations at residues associated with drug resistance and/or immune escape (i.e., G145R) were detected in a minor percentage of the population. Summary HBV genomes and drug resistant variants were detectable in PBMC subsets from HBV mono-infected individuals. The HBV replicates in PBMC subsets of HBV/HIV-1 patients except the CD4+ T cell subpopulation.     

Patients with chronic hepatitis B infection display deficiency of plasmacytoid dendritic cells with reduced expression of TLR9

Chronic hepatitis B virus (HBV) infection is a complex interaction between replicating noncytopathic virus and dysregulatory host antiviral immunity. Plasmacytoid dendritic cells (pDCs) contribute to innate antiviral immunity via secreting type I interferons. Toll-like receptor (TLR) 9 is involved in major pattern recognition receptors expressed in pDCs. The frequency of pDCs and TLR9 expression in peripheral blood mononuclear cells (PBMC) was determined, using flow cytometry. IFN-α production by PBMC was evaluated in vitro in the presence of cytidine phosphate guanosine (CpG) with/without pDCs. The correlation between TLR9, pDCs frequency and viral load was also evaluated. TLR9 expression in pDCs in chronic HBV patients was significantly (∼50%) reduced, supported by ∼70% reduction of TLR9 mRNA, in comparison to healthy controls, correlating with the impairment of IFN-α production in vitro. Furthermore, pDCs frequency in these patients was substantially reduced (∼30%), inversely correlating with serum ALT levels and HBV viral load. HBsAg and HBcAg were detected by immunohistochemistry in pDCs in chronic HBV patients. We conclude that HBV infection results in reduced frequency of circulating pDCs and their functional impairment via inhibiting the expression of TLR9. These data may provide useful information in both basic research and clinical treatment of chronic HBV infection.     

Circulating and liver resident CD4+CD25+ regulatory T cells actively influence the antiviral immune response and disease progression in patients with hepatitis B

CD4+CD25+ regulatory T cells (Treg) have been shown to maintain immune tolerance against self and foreign Ags, but their role in persistent viral infection has not been well-defined. In this study, we investigated whether and where CD4+CD25+ Treg contribute to the development of chronic hepatitis B (CHB). One hundred twenty-one patients were enrolled, including 16 patients with acute hepatitis B, 76 with CHB, and 29 with chronic severe hepatitis B. We demonstrated that in chronic severe hepatitis B patients, the frequencies of CD4+CD25+ Treg in both PBMC and liver-infiltrating lymphocytes were significantly increased and there was a dramatic increase of FoxP3(+)-cell and inflammatory cell infiltration in the liver compared with healthy controls. In CHB patients, circulating CD4+CD25+ Treg frequency significantly correlates with serum viral load. In acute hepatitis B patients, circulating CD4+CD25+ Treg frequency was initially low and with time, the profile reversed to exhibit an increased number of circulating Treg in the convalescent phase and restored to normal levels upon resolution. In PBMC taken from infected patients, depletion of CD4+CD25+ Treg led to an increase of IFN-gamma production by HBV-Ag-stimulated PBMC. In addition, CD4+CD25+ Treg were capable of suppressing proliferation of autologous PBMC mediated by HBV Ags, which probably reflects the generation of HBV-Ag-specific Treg in circulation and in the liver of HBV-infected patients. Together, our findings suggest that CD4+CD25+ Treg play an active role not only in modulating effectors of immune response to HBV infection, but also in influencing the disease prognosis in patients with hepatitis B.     

不同临床类型乙型病毒感染者外周血T 细胞亚群与血清HBV DNA 载量 及HBeAg 滴度相关性分析

目的:探讨慢性乙型肝炎病毒(HBV)感染患者外周血T细胞亚群与血清HBV DNA载量及HbeAg滴度的关系。方法:选取103名HBV感染患者和20名健康者为研究对象。流式细胞术检测外周血T细胞亚群,聚合酶链式反应及酶免疫分析法分别检测血清HBV DNA载量及HbeAg滴度。结果:慢性乙型肝炎患者和慢性HBV携带者外周血CD3+T、CD4+T淋巴细胞亚群百分数低于健康对照组,结果有统计学意义(P<0.05或0.01;而CD8+T细胞亚群则呈现相反趋势,结果亦有统计学意义(P<0.05或0.01)。HBeAg阴性组中,HBVDNA水平与CD8+T细胞亚群百分数呈正相关(r=0.567,P<0.01),与CD4+/CD8+T细胞亚群百分数比值呈负相关(r=-0.601,P<0.01),而与CD3+T、CD4+T细胞亚群百分数无相关性。HBeAg阳性组中,HBV DNA水平及HbeAg滴度与CD3+T、CD4+T、CD8+T细胞百分数及CD4+/CD8+T细胞百分数均无相关性(P>0.05)。结论:不同临床类型的慢性乙型肝炎病毒感染患者外周血T细胞亚群存在不同程度细胞免疫功能降低和细胞免疫调节异常。HbeAg阴性的HBV感染患者,其血清HBV DNA水平与外周血T淋巴细胞免疫存在相关性。     

不同临床类型乙型病毒感染者外周血T细胞亚群与血清HBVDNA载量及HBeAg滴度相关性分析

目的：探讨慢性乙型肝炎病毒（HBV）感染患者外周血T细胞亚群与血清HBVDNA载量及HbeAg滴度的关系。方法：选取103名HBV感染患者和20名健康者为研究对象。流式细胞术检测外周血T细胞亚群,聚合酶链式反应及酶免疫分析法分别检测血清HBVDNA载量及HbeAg滴度。结果：慢性乙型肝炎患者和慢性HBV携带者外周血CD3可、CD4T淋巴细胞亚群百分数低于健康对照组,结果有统计学意义（P〈0．05或0．01;而CD8＋T细胞亚群则呈现相反趋势,结果亦有统计学意义（P〈0．05或0．01）。HBeAg阴性组中,HBVDNA水平与CD8T细胞亚群百分数呈正相关（r=0．567,P〈0．01）,与CD47CD8＋T细胞亚群百分数比值呈负相关（r=-0．601,P〈0．01）,而与CD3＋T、CD4＋T细胞亚群百分数无相关性。HBeAg阳性组中,HBVDNA水平及HbeAg滴度与cD3＋1r、cD41、CD8叮细胞百分数及CD47CD8＋T细胞百分数均无相关性（P〉0．05）。结论：不同临床类型的慢性乙型肝炎病毒感染患者外周血T细胞亚群存在不同程度细胞免疫功能降低和细胞免疫调节异常。HbeAg阴性的HBV感染患者,其血清HBVDNA水平与外周血T淋巴细胞免疫存在相关性。     

Cellular immune response to hepatitis B virus-encoded antigens in acute and chronic hepatitis B virus infection

The proliferative response of PBMC to hepatitis B virus (HBV) envelope, core, and e Ag was analyzed prospectively in 21 patients with acute self-limited HBV infection and compared with the response of patients with chronic HBV infection and different levels of HBV replication (i.e., hepatitis e Ag (HBeAg)- or anti-HBe-positive) and liver damage (i.e., chronic active hepatitis or chronic asymptomatic carriers). Our results indicate that: 1) HBV-infected subjects who develop a self-limited acute hepatitis show a vigorous PBMC response to hepatitis B core Ag and HBeAg, as expression of T cell activation; 2) appearance of a detectable lymphocyte response to HBV nucleocapsid Ag is temporally associated with the clearance of HBV envelope Ag; 3) in patients with chronic HBV infection the level of T cell responsiveness to hepatitis B core Ag and to HBeAg is significantly lower than that observed during acute infection; 4) T cell sensitization to HBV envelope Ag in acute and chronic HBV infection is usually undetectable and when measurable is expressed transiently and at low levels. These results may reflect immune events of pathogenetic relevance with respect to evolution of disease and viral clearance.     

Characterization of hepatitis B virus (HBV)-specific T-cell dysfunction in chronic HBV infection

Dysfunctional CD8+ T cells present in chronic virus infections can express programmed death 1 (PD-1) molecules, and the inhibition of the engagement of PD-1 with its ligand (PD-L1) has been reported to enhance the antiviral function of these T cells. We took advantage of the wide fluctuations in levels of viremia which are typical of chronic hepatitis B virus (HBV) infection to comprehensively analyze the impact of prolonged exposure to different virus quantities on virus-specific T-cell dysfunction and on its reversibility through the blocking of the PD-1/PD-L1 pathway. We confirm that chronic HBV infection has a profound effect on the HBV-specific T-cell repertoire. Despite the use of a comprehensive panel of peptides covering all HBV proteins, HBV-specific T cells were rarely observed directly ex vivo in samples from patients with chronic infection, in contrast to those from patients with acute HBV infection. In chronic HBV infection, virus-specific T cells were detected mainly in patients with lower levels of viremia. These HBV-specific CD8+ T cells expressed PD-1, and their function was improved by the blocking of PD-1/PD-L1 engagement. Thus, a broad spectrum of anti-HBV immunity is expressed by patients with chronic HBV infection and this spectrum is proportional to HBV replication levels and can be improved by blocking the PD-1/PD-L1 pathway. This information may be useful for the design of immunotherapeutic strategies to complement and optimize available antiviral therapies.