慢性乙型肝炎患者外周血T淋巴细胞表面共刺激分子表达量变化及其意义
만성을형간염환자외주혈T림파세포표면공자격분자표체량변화급기의의
The significance of the co-stimulatory molecules expression atternation in the peripharal T lymphocytes of patients with chronic hepatitis B infection
  • 万方数据
    中华检验医学杂志 중화검험의학잡지
    CHINESE JOURNAL OF LABORATORY MEDICINE
    2014年 2期 105-109 ,共5页

    王琳%赵春楠%祁松楠%彭群新%史进方%顾国浩

    왕림%조춘남%기송남%팽군신%사진방%고국호

    肝炎,乙型,慢性%T淋巴细胞%抗原,CD28%CTLA-4抗原%膜蛋白质类%流式细胞术 肝炎,乙型,慢性%T淋巴細胞%抗原,CD28%CTLA-4抗原%膜蛋白質類%流式細胞術
    간염,을형,만성%T림파세포%항원,CD28%CTLA-4항원%막단백질류%류식세포술
    Hepatitis B,chronic%T-lymphocytes%Antigens,CD28%CTLA-4 antige%Membrane proteins%Flow cytometry
    目的 探讨慢性乙型肝炎患者外周血T淋巴细胞表面共刺激分子的表达量变化及其意义.方法 临床病例对照研究.收集2012年10月至2013年1 1月在苏州大学附属第一医院感染科住院的慢性乙型肝炎患者82例,其中男50例,女32例,年龄(42.25±14.22)岁,健康对照组30名来自本院预防保健科,其中男15例,女15例,年龄(42.32±3.74)岁；采用流式细胞术和定量PCR等技术测定慢性乙型肝炎患者外周血T淋巴细胞表面CD28、CTLA-4、PD-1、Tim-3的表达、T淋巴细胞亚群(CD4+、CD8+、CD4 +/CD8+),其中未经抗病毒及相关免疫治疗的有40例,经过抗病毒治疗有效的有30例,无效的12例,并结合HBV病毒载量、乙型肝炎e抗原和丙氨酸转氨酶等指标作综合分析.组间比较采用单因素方差分析和Kruskal-Wallis H检验,两样本均数的比较采用t检验和Mann-Whitney U检验,相关分析用Spearman'S检验.结果 CD4+ CD28+组间表达量健康对照组最高[404.65(331.65～536.09)],治疗无效组最低[277.15(249.90～344.25)],差异有统计学意义(H=29.81,P＜0.001)；CD4+ PD-1+组间表达量未治疗组最高[32.89 (29.69 ～ 39.69)],治疗无效组最低[19.26(11.90 ～20.56)],差异有统计学意义(H =43.13,P＜0.001)；CD8+ PD-1+组间表达量未治疗组最高[15.47(12.50 ～17.78)],健康对照组最低[3.05(1.41 ～ 3.97)],差异有统计学意义(H=56.60,P＜0.001)；CD4+ Tim-3+组间表达量治疗无效组最高[199.62(55.61 ～239.45)]、健康对照组最低[70.62(53.88 ～ 112.32)],差异有统计学意义(H=41.03,P＜0.001)；CD8+ Tim-3+组间表达量未治疗组最高[82.50(78.69 ～84.58)],健康对照组最低[3.07(1.56 ～6.87)],差异有统计学意义(H=74.84,P＜0.001)；与低病毒载量组相比,治疗前CD8+ PD-1+在高病毒载量组中的表达量17.87(13.38 ～20.94)]升高,差异有统计学意义(U=25.00,P＜0.001),治疗后CD8+ PD-1+在高病毒载量组中的表达量[16.95(5.39 ～ 18.27)]升高,差异有统计学意义(U=63.50,P＜0.001)；治疗后PD-1表达量与ALT也有明显的正相关性,其中CD4+ PD-1+(r=0.689,P＜0.001)、CD8+ PD-1+(r =0.751,P＜0.001).结论 在慢性乙型肝炎患者抗病毒治疗过程中,可能伴随有CD28、PD-1、CTLA-4和Tim-3的异常表达.共刺激分子的检测可为临床合理治疗慢性乙肝提供新线索.
    목적 탐토만성을형간염환자외주혈T림파세포표면공자격분자적표체량변화급기의의.방법 림상병례대조연구.수집2012년10월지2013년1 1월재소주대학부속제일의원감염과주원적만성을형간염환자82례,기중남50례,녀32례,년령(42.25±14.22)세,건강대조조30명래자본원예방보건과,기중남15례,녀15례,년령(42.32±3.74)세；채용류식세포술화정량PCR등기술측정만성을형간염환자외주혈T림파세포표면CD28、CTLA-4、PD-1、Tim-3적표체、T림파세포아군(CD4+、CD8+、CD4 +/CD8+),기중미경항병독급상관면역치료적유40례,경과항병독치료유효적유30례,무효적12례,병결합HBV병독재량、을형간염e항원화병안산전안매등지표작종합분석.조간비교채용단인소방차분석화Kruskal-Wallis H검험,량양본균수적비교채용t검험화Mann-Whitney U검험,상관분석용Spearman'S검험.결과 CD4+ CD28+조간표체량건강대조조최고[404.65(331.65～536.09)],치료무효조최저[277.15(249.90～344.25)],차이유통계학의의(H=29.81,P＜0.001)；CD4+ PD-1+조간표체량미치료조최고[32.89 (29.69 ～ 39.69)],치료무효조최저[19.26(11.90 ～20.56)],차이유통계학의의(H =43.13,P＜0.001)；CD8+ PD-1+조간표체량미치료조최고[15.47(12.50 ～17.78)],건강대조조최저[3.05(1.41 ～ 3.97)],차이유통계학의의(H=56.60,P＜0.001)；CD4+ Tim-3+조간표체량치료무효조최고[199.62(55.61 ～239.45)]、건강대조조최저[70.62(53.88 ～ 112.32)],차이유통계학의의(H=41.03,P＜0.001)；CD8+ Tim-3+조간표체량미치료조최고[82.50(78.69 ～84.58)],건강대조조최저[3.07(1.56 ～6.87)],차이유통계학의의(H=74.84,P＜0.001)；여저병독재량조상비,치료전CD8+ PD-1+재고병독재량조중적표체량17.87(13.38 ～20.94)]승고,차이유통계학의의(U=25.00,P＜0.001),치료후CD8+ PD-1+재고병독재량조중적표체량[16.95(5.39 ～ 18.27)]승고,차이유통계학의의(U=63.50,P＜0.001)；치료후PD-1표체량여ALT야유명현적정상관성,기중CD4+ PD-1+(r=0.689,P＜0.001)、CD8+ PD-1+(r =0.751,P＜0.001).결론 재만성을형간염환자항병독치료과정중,가능반수유CD28、PD-1、CTLA-4화Tim-3적이상표체.공자격분자적검측가위림상합리치료만성을간제공신선색.
    Objective To investigate the significance of changes in expression of co-stimulatory molecules on T lymphocytes in patients with chronic hepatitis B (CHB) infection.Methods In a casecontrol study,a total of 82 CHB cases including 50 male cases and 32 female cases (the mean age was 42.32 ±3.74) were enrolled in the First Affiliated Hospital to Soochow University from October 2012 to November 2013,together with 30 cases health control (15 male cases and 15 female cases,and the mean age was 42.32 ± 3.74).Patients were divided into three groups:40 cases of non-treated,30 cases of effective-treated and 12 cases of ineffective-treated with anti-viral drugs and immune-related therapy.The expression levels of CD28,CTLA-4,PD-1,Tim-3 on T cells subset from peripheral blood were determined by Flow Cytometry.Serum load of HBV DNA was detected by Real-time PCR and the serology markers such as HBeAg and ALT were detected by conventional methods The Kruskal-Wallis test was used to analysis groups comparison.Independent samples t-test and Mann-Whitney U test were used to two sample comparison.Spearman's rank correlation test was used to analyze the correlation.Results The expression levels of CD28,CTLA-4 and PD-1 on CD4 in health control group was the highest compared to ineffectivetreated group [404.65 (331.65-536.09) vs 277.15 (249.90-344.25) (H=29.81,P＜0.001);32.89 (29.69-39.69) vs 19.26 (11.90-20.56) (H =43.13,P ＜0.001),respectively].The expression level of PD-1 on CD8 in pre-treated group was the highest,while expression level in health control group was the lowest [15.47 (12.50-17.78) vs 3.05 (1.41-3.97) (H=56.60,P＜0.001)].Similarly,the expression level of Tim-3 on CD4 in ineffective-treated group was the highest,while Tim expression on CD4 in health control group was the lowest [199.62 (55.61-239.45) vs 70.62 (53.88-112.32) (H =41.03,P ＜ 0.001)].The expression level of Tim-3 on CD8 in pre-treated group was the highest,while it was the lowest in health control group [82.50 (78.69-84.58) vs 3.07 (1.56-6.87) (H=74.84,P ＜0.001)].Compared to the group with low viral load,the expression level of PD-1 on CD8 both in the pre-treated group with high viral load and the post-treated group was significantly increased [17.87 (13.38-20.94) (U=25.00,P＜0.001); 16.95 (5.39-18.27) (U=63.50,P＜0.001),respectively].Importantly,in the post-treated group,the PD-1 expression on CD4 T (r =0.689,P ＜0.001) and on CD8 T (r =0.751,P ＜ 0.001) was also positively correlated with ALT.Conclusions The abnormal expression of these co-stimulatory molecules may be present in the antiviral treatment process of CHB.It may provide new clues for the reasonable treatment of CHB.
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