慢性HBV感染者外周血可诱导共刺激分子在CD8+ T淋巴细胞的表达及其临床意义

Expression of ICOS in CD8+T Lymphocytes in Peripheral Blood of Patients with Chronic HBV Infection and Its Clinical Significance

目的 探讨慢性乙型肝炎病毒(HBV)感染者外周血可诱导共刺激分子(ICOS)在CD8+T淋巴细胞的表达特点及临床意义。方法 选取2017年5月—2018年10月就诊的慢性乙型肝炎(CHB)100例、HBV-肝硬化(LC)25例和HBV-慢加急(或亚急)性肝衰竭(ACLF)26例分别纳入CHB组、HBV-LC组和HBV-ACLF组,健康对照(NC)组35例来自同期门诊体检健康者。采用流式细胞仪检测各组ICOS在CD8+T淋巴细胞的表达情况;分析CD8+T淋巴细胞ICOS表达水平与慢性HBV感染者疾病严重程度、HBV-ACLF预后及并发症的相关性;动态观察HBV-ACLF患者治疗过程中CD8+T淋巴细胞ICOS表达变化。结果 HBV-ACLF组外周血CD8+T淋巴细胞ICOS表达比率及平均荧光强度(MFI)均高于CHB组、HBV-LC组和NC组(P<0.05)。慢性HBV感染者ICOS的MFI与白蛋白、胆碱酯酶、总胆固醇、血红蛋白呈负相关(r=-0.263、-0.269、-0.273、-0.302,P=0.003、0.003、0.011、0.004);与直接胆红素、天冬氨酸转氨酶、凝血酶原时间、国际标准化比值呈正相关(r=0.248、0.208、0.331、0.315,P=0.005、0.020、0.003、0.009);与HBV-DNA、腹水及感染无明显相关性(P>0.05)。治疗过程中,HBV-ACLF患者ICOS的MFI无明显改变。但生存组ICOS的MFI在治疗第1周时较治疗前上升(P<0.05)。结论 HBV-ACLF患者外周血CD8+T淋巴细胞ICOS的表达水平明显升高,并与肝脏合成功能、炎症程度及预后相关,治疗早期ICOS水平变化有助于预测慢性HBV感染者的预后。

Objective To investigate the expression characteristics and clinical significance of inducible costimulatory molecule(ICOS)in CD8+T lymphocytes in peripheral blood of patients with chronic hepatitis B virus(HBV).Methods From May 2017 to October 2018,100 patients with chronic hepatitis B(CHB),25 patients with HBV-liver cirrhosis(LC)and 26 patients with HBV-acute-on-chronic(or subacute)liver failure(ACLF)were selected and included in the CHB group,HBV-LC group and HBV-ACLF group,respectively.In the healthy control(NC)group,35 people were healthy physical examinees during the same period.The expression of ICOS in CD8+T lymphocytes was detected by flow cytometry.The correlation between ICOS expression level of CD8+T lymphocytes and disease severity,prognosis and complications in patients with chronic HBV infection was analyzed.Changes in ICOS expression of CD8+T lymphocytes in HBV-ACLF patients was dynamically observed during treatment.Results The ICOS expression ratio and mean fluorescence intensity(MFI)of CD8+T lymphocytes in peripheral blood of HBV-ACLF patients were higher than those in CHB,HBV-LC and NC groups(P<0.05).The MFI of ICOS in CD8+T lymphocytes of patients with chronic HBV infection was negatively correlated with albumin,cholinesterase,total cholesterol and hemoglobin(r=-0.263,-0.269,-0.273,-0.302,P=0.003,0.003,0.011,0.004),and positively correlated with direct bilirubin,aspartate aminotransferase,prothrombin time and international standardized ratio(r=0.248,0.208,0.331,0.315,P=0.005,0.020,0.003,0.009);however,it had no significant correlation with HBV-DNA,ascites and infection(P>0.05).During treatment,the MFI of ICOS in CD8+T lymphocyte of HBV-ACLF patients did not change significantly.However,the MFI of ICOS in CD8+T lymphocyte in survival group was higher at the first week of treatment than that before treatment(P<0.05).Conclusion ICOS expression level of CD8+T lymphocytes in peripheral blood of HBV-ACLF patients is significantly increased,and is related to liver synthesis function,inflammation degree and prognosis.Changes in ICOS level in early treatment can help predict the prognosis of patients with chronic HBV infection.