慢性乙型肝炎患者血清中sICOS和sPD-1升高及意义

基础医学与临床 ›› 2015, Vol. 35 ›› Issue (7): 916-920.

慢性乙型肝炎患者血清中sICOS和sPD-1升高及意义

王东生¹,²,杜琴²,刘彦信³,张国元²,郑德先³

1. 北京协和医学院
2. 川北医学院附属医院
3. 中国医学科学院基础医学研究所

收稿日期:2015-05-11 修回日期:2015-05-19 出版日期:2015-07-05 发布日期:2015-06-23
通讯作者: 郑德先 E-mail:zhengdx@pumc.edu.cn
基金资助:
驼羊单抗用于重大疾病早期诊断的联合研究

Expression and significance of sICOS/sPD-1 in the serum of patients with chronic hepatitis B

Received:2015-05-11 Revised:2015-05-19 Online:2015-07-05 Published:2015-06-23

摘要/Abstract

摘要： 目的：检测慢性乙型肝炎(CHB)患者血清中可溶性可诱导共刺激分子(sICOS)和可溶性程序性死亡蛋白1(sPD-1)的蛋白水平，并初步探讨其意义。方法：收集80例CHB患者和30例健康对照者，外周血单个核细胞(PBMCs)和血液上清。根据HBsAg和HBeAg测定值，将CHB患者分为HBeAg(-)和HBeAg(+)两组；并将HBeAg(+)组分为免疫耐受期和免疫清除期。用ELISA 法检测以上研究对象外周血上清中sICOS和sPD-1蛋白浓度。用实时荧光定量PCR检测PBMCs中ICOS、PD-1和PD-1Δex3的表达。结果：与对照相比，sICOS在CHB患者中均增高(p<0.05)；而sPD-1仅在HBeAg(+)组显著增高(p<0.01)，其中免疫清除期比免疫耐受期患者增高更明显(p<0.05)。 CHB患者的 sPD-1与AST呈正相关(p<0.01)；且HBeAg(+)组的sPD-1与ALT呈正相关(p<0.01)； CHB患者的 sICOS与HBV-DNA呈弱的负相关性(p<0.05)。活化前，两组CHB患者的ICOS mRNA表达水平均降低(p<0.05)；结论：sICOS和sPD-1在CHB患者的血清中均异常增高，提示sICOS和sPD-1可能参与了CHB的发生发展。

关键词: ICOS, PD-1, 慢性乙型肝炎

Abstract: Objective:To detect the level of soluble inducible co-stimulator molecule (sICOS) and soluble programmed death protein 1 (sPD-1) in peripheral blood supernatant in patients with chronic hepatitis B and then discuss its significance with other index. Methods: Eighty patients with CHB and thirty healthy persons were enrolled in our study. the peripheral blood supernatant were collected and isolated the peripheral blood mononuclear cells (PBMCs) in CHB patients . According to the clinical HBsAg and HBeAg results, the CHB patients can be divided into the HBeAg(-) group and the HBeAg(+) group, simultaneously,the HBeAg(+) group was divided into two parts: the immune tolerance group and immune clearance group.The sICOS and sPD-1 expression in the peripheral blood was measured by enzyme-linked immunosorbent assay (ELISA).the mRNA expression of ICOS、PD-1 and PD-1Δex3 in PBMCs of patients with CHB were detected by real-time quantitative reverse transcription polymerase chain reaction(RT-qPCR). Results sICOS level was significantly higher in CHB patients compairing the healthy controls(p<0.05); as same as the HBeAg(+) persons , sPD-1 was increased(p<0.01), in which the sPD-1 level was increased more obviously in patients who were in immune clearance phase than those in immune tolerance phase(p<0.05). sPD-1 was positively correlated with the AST levels in CHB patients( p<0.01); The sPD-1 was only correlated with the ALT levels in the HBeAg(+) patients( p<0.01). But there is no correlation between sICOS levels and the ALT or AST levels.A weakly negative correlation between HBV-DNA and sICOS levels was observed (p<0.05). Whereas the sICOS did not correlate with HBeAg levels.Compared with the healthy controls, before the activation and stimulation, the ICOS mRNA expression were decreased in two CHB groups (p<0.05).Conclusion:The sICOS and sPD-1 levels were significantly higher in the serum of patients with CHB and they may be able to participate in the development of CHB.

Key words: ICOS, PD-1, chronic hepatis B

王东生杜琴刘彦信张国元郑德先. 慢性乙型肝炎患者血清中sICOS和sPD-1升高及意义[J]. 基础医学与临床, 2015, 35(7): 916-920.