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目的观察慢性乙型肝炎病毒(HBV)感染处于不同自然史患者外周血T淋巴细胞表面淋巴细胞活化基因3(LAG-3)表达的变化,探讨抑制性受体LAG-3在T细胞的表达变化与处于不同自然史慢性HBV感染者血清丙氨酸氨基转移酶(ALT)、乙型肝炎病毒(HBV)e抗原(HBe Ag)和HBV DNA水平的关系。方法选取处于慢性HBV感染自然史为免疫耐受期(IT)患者24例、免疫清除期(IC)32例和非活动或低复制期(LR)患者31例,健康体检者30例为正常对照(HC)。应用流式细胞术检测外周血CD8+T细胞和CD4+T细胞表达LAG-3的比例;免疫分析法、生化分析法和PCR分别检测患者肝脏功能、HBV血清学标志物和HBV DNA水平。采用Mann-Whitney U检验分析各组间T细胞LAG-3表达率的差异;Spearman等级相关性分析各期慢性HBV感染患者外周血T细胞LAG-3表达阳性率与血清ALT、HBV DNA和HBe Ag水平的相关性。结果慢性HBV感染者外周血LAG-3+CD8+T细胞的比例较HC组显著增高,且处于IT期的患者外周血LAG-3+CD8+T细胞的比例明显高于IC期或LR期患者及HC组。处于IC期患者外周血LAG-3+CD8+T细胞和LAG-3+CD4+T细胞比例与患者血清中ALT水平呈显著负相关;IT组患者外周血LAG-3+CD8+T细胞和LAG-3+CD4+T细胞比例与血清中HBe Ag呈正相关。然而,不同自然史慢性HBV感染患者外周血LAG-3+CD4+T细胞比例和LAG-3+CD8+T细胞比例与血清HBV DNA水平无相关性。结论 LAG-3在慢性HBV感染患者外周血CD8+T细胞高表达,尤其是IT期患者CD8+T细胞高表达,可能是造成CD8+T细胞功能低下、HBV在肝脏长期复制的重要因素之一。
Objective To investigate the expression of LAG-3 in peripheral blood of patients with chronic hepatitis B virus (HBV) infection in different natural history and to investigate the expression of LAG-3 in T cells And serum alanine aminotransferase (ALT), hepatitis B virus e antigen (HBeAg) and HBV DNA levels in patients with chronic HBV infection of different natural history. Methods Twenty-four patients with natural history of chronic HBV infection were immunocompromised (IT), 32 patients were immunosuppressed (IC), 31 patients were inactive or low-replication (LR), and 30 healthy controls were selected as normal controls (HC). Flow cytometry was used to detect the ratio of LAG-3 expression in peripheral blood CD8 + T cells and CD4 + T cells. Immunoassay, biochemical analysis and PCR were used to detect liver function, HBV serology markers and HBV DNA levels. The Mann-Whitney U test was used to analyze the difference of LAG-3 expression rate among different groups. Spearman rank correlation analysis was used to analyze the positive rate of LAG-3 expression in peripheral blood T lymphocytes in patients with chronic HBV infection and serum ALT, HBV DNA and HBeAg Horizontal correlation. Results The proportion of LAG-3 + CD8 + T cells in peripheral blood of patients with chronic HBV infection was significantly higher than that of HC patients, and the proportion of LAG-3 + CD8 + T cells in peripheral blood of patients with IT was significantly higher than those in patients with IC or LR And HC group. The ratio of LAG-3 + CD8 + T cells and LAG-3 + CD4 + T cells in peripheral blood of IC patients was significantly negatively correlated with the level of ALT in the serum of patients with IC; LAG-3 + CD8 + T cells and LAG The proportion of -3 + CD4 + T cells was positively correlated with HBe Ag in serum. However, the proportion of LAG-3 + CD4 + T cells and LAG-3 + CD8 + T cells in peripheral blood of patients with chronic HBV infection with different natural history had no correlation with serum HBV DNA levels. Conclusions LAG-3 is highly expressed in peripheral blood of patients with chronic HBV infection, especially CD8 + T cells in IT patients, which may be one of the important factors that cause CD8 + T cell dysfunction and long-term HBV replication in the liver .