CAJ | 학술논문

目的探讨可溶性程序性死亡配体1(sPD-L1)在结核性胸膜炎患者胸腔积液和外周血中的表达及意义.方法筛选2012年6月至2013年3月苏州大学附属第二医院呼吸科收治的初诊胸腔积液患者,根据积液性质分为结核、恶性及非结核、非恶性3组.酶联免疫吸附(ELISA)法检测各组患者胸腔积液和外周血中sPD-L1含量,流式细胞术检测胸腔积液中免疫细胞亚群的变化,反转录PCR法检测胸腔积液中程序性死亡配体1(PD-L1)含量、基质金属蛋白酶3(MMP-3)基因表达,并进行统计学对比分析.结果共纳入初诊胸腔积液患者77例,其中结核组24例,恶性组39例,非结核、非恶性组14例.结核组胸腔积液中sPD-L1含量显著高于恶性组和非结核、非恶性组[4.2(2.6～6.3)比1.4(0.8～2.1)和1.8(1.2 ～2.6)μg/L,P＜0.001];而3组患者外周血sPD-L1含量差异无统计学意义(P =0.811).所有患者胸腔积液的sPD-L1平均含量显著高于外周血[2.0(1.4 ～3.7)比1.5(1.0 ～2.0)μg/L,P=0.004].结核组胸腔积液中CD8+细胞比例、PD-L1在CD14+单核细胞表达(CD14+-PD-L1)比例、PD-L1 mRNA表达均高于恶性组及非结核、非恶性组(P =0.001、P＜0.001、P＜0.001),且PD-L1 mRNA与MMP-3表达水平相关(r=0.887,P＜0.001).受试者工作特征(ROC)曲线分析显示,单因素检测胸腔积液sPD-L1诊断结核性胸腔积液的敏感度为82.6％,特异度为83.8％,曲线下面积为0.854;胸腔积液sPD-L1、CD14+-PD-L1及腺苷脱氨酶联合检测诊断结核性胸腔积液的敏感度为91.3％,特异度为89.2％,曲线下面积为0.989.结论结核性胸腔积液中sPD-L1异常增高,检测sPD-L1有助于对此类患者的诊断.
목적 탐토가용성정서성사망배체1(sPD-L1)재결핵성흉막염환자흉강적액화외주혈중적표체급의의.방법 사선2012년6월지2013년3월소주대학부속제이의원호흡과수치적초진흉강적액환자,근거적액성질분위결핵、악성급비결핵、비악성3조.매련면역흡부(ELISA)법검측각조환자흉강적액화외주혈중sPD-L1함량,류식세포술검측흉강적액중면역세포아군적변화,반전록PCR법검측흉강적액중정서성사망배체1(PD-L1)함량、기질금속단백매3(MMP-3)기인표체,병진행통계학대비분석.결과 공납입초진흉강적액환자77례,기중결핵조24례,악성조39례,비결핵、비악성조14례.결핵조흉강적액중sPD-L1함량현저고우악성조화비결핵、비악성조[4.2(2.6～6.3)비1.4(0.8～2.1)화1.8(1.2 ～2.6)μg/L,P＜0.001];이3조환자외주혈sPD-L1함량차이무통계학의의(P =0.811).소유환자흉강적액적sPD-L1평균함량현저고우외주혈[2.0(1.4 ～3.7)비1.5(1.0 ～2.0)μg/L,P=0.004].결핵조흉강적액중CD8+세포비례、PD-L1재CD14+단핵세포표체(CD14+-PD-L1)비례、PD-L1 mRNA표체균고우악성조급비결핵、비악성조(P =0.001、P＜0.001、P＜0.001),차PD-L1 mRNA여MMP-3표체수평상관(r=0.887,P＜0.001).수시자공작특정(ROC)곡선분석현시,단인소검측흉강적액sPD-L1진단결핵성흉강적액적민감도위82.6％,특이도위83.8％,곡선하면적위0.854;흉강적액sPD-L1、CD14+-PD-L1급선감탈안매연합검측진단결핵성흉강적액적민감도위91.3％,특이도위89.2％,곡선하면적위0.989.결론 결핵성흉강적액중sPD-L1이상증고,검측sPD-L1유조우대차류환자적진단.
Objective To explore the level of soluble programmed death ligand 1 (sPD-L1) in pleural effusion and peripheral blood of patients with tuberculous pleural effusion (TPE) and elucidate its clinical implications.Methods Patients with newly diagnosed pleural effusion at the Second Affiliated Hospital of Soochow University from June 2012 to March 2013 were enrolled and divided into 3 groups of TPE,malignant pleural effusion (MPE) and non-tuberculous non-malignant pleural effusion (non-TPE nonMPE) according to the nature of pleural effusion.The level of sPD-L1 in pleural effusion and peripheral blood was analyzed by enzyme linked immunosorbent assay (ELISA) kit.Flow cytometry was used to detect the changes of immune cell subsets in pleural effusion.And the gene expressions of programmed death ligand 1 (PD-L1) and matrix metalloproteinase-3 (MMP-3) were detected in different effusions by reverse transcription-polymerase chain reaction (RT-PCR).Results A total of 77 newly diagnosed patients with pleural effusion were enrolled,24 patients with TPE,39 patients with MPE,14 patients with non-TPE nonMPE.The level of sPD-L1 in TPE was higher than that in MPE and non-TPE non-MPE (4.2 (2.6-6.3),1.4 (0.8-2.1),1.8 (1.2-2.6) μg/L,P ＜ 0.001).No significant difference existed in the levels of sPD-L1 in peripheral blood samples (P =0.811).The average content of sPD-L1 in pleural effusion in all patients was statistically higher than that in peripheral blood (2.0 (1.4-3.7),1.5 (1.0-2.0) μg/L,P=0.004).The proportion of CD8 subset,PD-L1 on CD14+ monocytes and the mRNA level of PD-L1,MMP-3 in TPE were higher than in MPE and non-TPE non-MPE (P =0.001,P ＜ 0.001,P ＜ 0.001),and the mRNA level of PD-L1 in TPE was positively correlated with the level of MMP-3 (r =0.887,P ＜0.001).Receiver operating characteristic (ROC) curve analysis showed that sPD-L1 had a sensitivity of 82.6％,a specificity of 83.8％ and an area under curve (AUC) of 0.854 for differential diagnosis of TPE from other conditions.Combinations of sPD-L1,PD-L1 on CD14 + monocytes and adenosine deaminase (ADA) measurements further increased the sensitivity up to 91.3％,specificity up to 89.2％ and AUC up to 0.989.Conclusion The elevated expression of sPD-L1 in tuberculous pleural effusion may aid the diagnosis of TPE.