PD-1和PD-L1表达在慢性乙型肝炎病毒不同感染阶段患者的PBMCs表面表达

Expression of PD-1 and PD-L1 in patients with different stages of chronic hepatitis B virus infection

目的通过检测不同慢性乙型肝炎病毒(HBV)感染阶段的患者外周血单核细胞(PBMCs)表面程序性死亡受体-1(PD-1)及其配体(PD-L1)的表达,探讨其与血清HBV-DNA载量、ALT之间的相关性。方法收集不同临床类型慢性HBV感染者80例,其中HBV携带者20例(A组),1×ULN≤ALT<2×ULN 20例(B组),2×ULN≤ALT<5×ULN 20例(C组),ALT≥5×ULN 20例(D组),健康献血者20例(E组)。采用流式细胞术检测外周血单核细胞(PBMCs)表面PD-1及其配体PD-L1表达,以实时荧光定量PCR检测血清HBVDNA,同时检测血清谷丙转氨酶(ALT)。结果 A、B、C、D组PBMCs表面PD-1、PD-L1表达显著高于E组(P<0.05);C、D组与A、B组间比较,PBMCs表面PD-1、PD-L1表达显著升高(P<0.05),C组与D组比较PBMCs表面PD-1、PD-L1表达水平差异无统计学意义(P>0.05);A组与B组比较,PBMCs表面PD-1、PD-L1表达水平差异无统计学意义(P>0.05)。不同慢性HBV感染阶段患者PBMCs表面PD-1、PD-L1表达水平与血清HBV-DNA载量间无相关性(r=0.271,P>0.05),但与ALT间有相关性(r=0.679,P<0.05)。结论慢性HBV不同感染阶段患者PBMCs表面PD-1、PD-L1表达与机体免疫状态有关,肝脏炎症损伤是影响PD-1、PD-L1表达的重要因素,HBV-DNA载量不是主要影响原因。

Objective To detect the expression of programmed death - 1 （programmed death - 1, PD - 1 ） and its ligand （pro- grammed death 1 ligand,PD- L1 ） in chronic hepatitis B virus （HBV） patients with different stages. And to investigate the correlation between PD - 1,PD - L1 expression, serum HBV - DNA load and serum ALT levels. Methods 80 cases were collected with different clinical types of chronic HBV infection. 20 cases （group A） were HBV carriers,1 × ULN ≤ ALT 〈 2 × ULN in 20 cases （ group B）, 2 ×ULN ≤ ALT 〈 5 x ULN in 20 cases （ Group C）, ALT ≥ 5 × ULN in 20 cases （ Group D） ,20 cases of healthy blood donors （ group E）. Flow cytometry was used to detect the expression of PD - 1 and ligand PD - L1 on the surface of PBMCs, real - time fluorescence quantitative PCR was detected the HBV - DNA in serum, and serum alanine aminotransferase （ALT） was detected simultaneously. Results PD - 1, PD - L1 expression in group A, group B, group C, group D was significantly higher than that in Group E （P 〈 0.05 ）. Compared with group A and group B, the expression of PD - 1 and PD -L1 in group C, group D was significantly increased （P 〈 0.05 ）. Compared with group D and group C, PBMCs had no significant difference in the expression level of PD - 1, PD - L1 （ P 〉 0.05 ）, group A compared with the group B, PBMCs surface PD - 1, PD - L1 expression levels were not significantly different （ P 〉 0. 05 ）. Correlation analysis showed that there was no correlation between the expression of PD - 1, PD - LI on PBMCs surface and the level of serum HBV - DNA in patients with chronic HBV infection （ r = 0.271, P 〉 0. 05 ）, But there was a correlation between ALT （ r = 0.679, P 〈 0. 05 ）. Conclusion Chronic HBV patients with different stages of infection PBMCs surface PD - 1, PD - L1 expression is related to the immune state of the body. Liver inflammatory damage is an important factor affecting the expression of PD - 1, PD - L1, HBV - DNA load is not the main cause of the impact.