Luo Liulin, Zhu Lin, Yue Jun, Liu Jianping, Liu Guoyuan, Zhang Xuelian, Wang Honghai, Xu Ying
State Key Laboratory of Genetic Engineering, Institute of Genetics, Fudan University, Shanghai 200433, China.
Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China.
Emerg Microbes Infect. 2017 Jul 12;6(7):e64. doi: 10.1038/emi.2017.54.
This study aimed to identify novel immunogenic epitopes from Mycobacterium tuberculosis (MTB) that could be used in tuberculosis (TB) diagnostics. To determine the diagnostic potential of mycobacterial antigens in serodiagnosis of TB, 256 patients were enrolled in a study and divided into two groups: 126 smear-positive pulmonary TB patients (SPPT) and 130 smear-negative pulmonary TB patients (SNPT); 152 bacillus Calmette-Guerin (BCG)-vaccinated healthy people were used as a control. Murine results showed that antigens Rv0310c-E from RD 8 and Rv1255c-E from RD 10 were strongly immunogenic to Th1 cells and induced a great humoral response. Receiver operating characteristic analysis indicated that Rv0310c-E (area under the curve (AUC): 0.800) and Rv1255c-E (AUC: 0.808) performed better than ESAT-6 (AUC: 0.665) and CFP-10 (AUC: 0.623) proteins but were comparable with Rv3425 (AUC: 0.788) protein in a human serum IgG analysis. Rv0310c-E demonstrated the highest diagnostic ability for the SPPT group (Youden index: 0.5602, sensitivity: 69.84%, specificity: 86.18%), while Rv1255c-E demonstrated the highest diagnostic ability for the SNPT group (Youden index: 0.5674, sensitivity: 73.84%, specificity: 82.89%). In addition, combination analysis found that antigen Rv0310c-E, coupled with the Rv3425 protein (Youden index: 0.6098, sensitivity: 87.30%, specificity: 73.68%) had the strongest performance for TB diagnostics of the SPPT group, and the single antigen Rv1255c-E was strongest for the SNPT group. These results suggest that antigens Rv0310c-E and Rv1255c-E are potential antigens for TB serodiagnostic tests, which may facilitate detection of MTB in smear-negative and smear-positive patients.
本研究旨在从结核分枝杆菌(MTB)中鉴定出可用于结核病(TB)诊断的新型免疫原性表位。为了确定分枝杆菌抗原在结核病血清学诊断中的潜力,256名患者参与了一项研究并被分为两组:126例涂片阳性肺结核患者(SPPT)和130例涂片阴性肺结核患者(SNPT);152名接种卡介苗(BCG)的健康人作为对照。小鼠实验结果表明,来自RD8的抗原Rv0310c - E和来自RD10的抗原Rv1255c - E对Th1细胞具有强烈的免疫原性,并诱导了强烈的体液反应。受试者工作特征分析表明,在人血清IgG分析中,Rv0310c - E(曲线下面积(AUC):0.800)和Rv1255c - E(AUC:0.808)的表现优于ESAT - 6(AUC:0.665)和CFP - 10(AUC:0.623)蛋白,但与Rv3425(AUC:0.788)蛋白相当。Rv0310c - E对SPPT组显示出最高的诊断能力(约登指数:0.5602,敏感性:69.84%,特异性:86.18%),而Rv1255c - E对SNPT组显示出最高的诊断能力(约登指数:0.5674,敏感性:73.84%,特异性:82.89%)。此外,联合分析发现,抗原Rv0310c - E与Rv3425蛋白联用(约登指数:0.6098,敏感性:87.30% ,特异性:73.68%)对SPPT组结核病诊断的表现最强,而单一抗原Rv1255c - E对SNPT组最强。这些结果表明,抗原Rv0310c - E和Rv1255c - E是结核病血清学诊断试验的潜在抗原,这可能有助于检测涂片阴性和涂片阳性患者中的MTB。