Establishment and preliminary application of optimal cut-off value of anti-multi-epitope fusion antigen IgG antibody of Mycobacterium tuberculosis

doi:10.3969/j.issn.1673-8640.2018.10.006

Abstract

Abstract:

Objective To establish an optimal cut-off value of anti-multi-epitope fusion antigen IgG antibody of Mycobacterium tuberculosis（MTB-Ab）,and to evaluate the diagnostic efficiency for pulmonary tuberculosis. Methods MTB-Ab was determined by enzyme-linked immunosorbent assay （ELISA）in 62 patients with active pulmonary tuberculosis,58 patients with inactive pulmonary tuberculosis and 168 healthy subjects （healthy control group）. The optimal cut-off value was confirmed as cut-off index （COI） by receiver operating characteristic （ROC） curve. The diagnostic efficiency of the cut-off value recommended by kit and optimal COI on pulmonary tuberculosis and active pulmonary tuberculosis was evaluated. Results Using healthy control group as control,the optimal COI₁ of MTB-Ab for the diagnosis of pulmonary tuberculosis was 0.90,and the sensitivity was 92.5%,which was higher than the sensitivity for the cut-off value（0.18） recommended by kit （86.7%）（P<0.05）. There was no statistical significance for specificity,Youden index,positive likelihood ratio,negative likelihood ratio,positive predictive value and negative predictive value between the cut-off value recommended by kit and COI₁ for the diagnosis of pulmonary tuberculosis （P>0.05）. Using inactive pulmonary tuberculosis group as control,the optimal COI₂ was 3.65,the sensitivity,specificity,Youden index,positive likelihood ratio,positive predictive value and negative predictive value were lower than those of COI₁（P<0.05）,and negative likelihood ratio was higher（P<0.05）. Conclusions Using healthy control group as control,the COI₁ of MTB-Ab as the cut-off value could improve the diagnostic sensitivity of pulmonary tuberculosis. Using inactive pulmonary tuberculosis group as control,the diagnostic efficiency of COI₂ for active and inactive pulmonary tuberculosis decreases.

Key words: Enzyme-linked immunosorbent assay, Tuberculosis antibody, Diagnostic efficiency

CLC Number:

R446.61

QI Yingjie, SHI Yuru, LIU Ting, YUE Li, ZHAO Changcheng, WANG Yun, MA Xiaoling. Establishment and preliminary application of optimal cut-off value of anti-multi-epitope fusion antigen IgG antibody of Mycobacterium tuberculosis[J]. Laboratory Medicine, 2018, 33(10): 899-902.

Figures/Tables 3

References 14

[1]	ZUMLA A,RAVIGLIONE M,HAFNER R,et al.Tuberculosis[J]. N Engl J Med,2013,368(8):745-755.
[2]	ZHU C,LIU J,LING Y,et al.Evaluation of the clinical value of ELISA based on MPT64 antibody aptamer for serological diagnosis of pulmonary tuberculosis[J]. BMC Infect Dis,2012,12:96.
[3]	TIWARI R P,HATTIKUDUR N S,BHARMAL R N,et al.Modern approaches to a rapid diagnosis of tuberculosis: promises and challenges ahead[J]. Tuberculosis (Edinb),2007,87(3):193-201.
[4]	COX J A,LUKANDE R L,LUCAS S,et al.Autopsy causes of death in HIV-positive individuals in sub-Saharan Africa and correlation with clinical diagnoses[J]. AIDS Rev,2010,12(4):183-194.
[5]	PETER J G,THERON G,VAN ZYL-SMIT R,et al. Diagnostic accuracy of a urine lipoarabinomannan strip-test for TB detection in HIV-infected hospitalised patients[J]. Eur Respir J,2012,40(5):1211-1220.
[6]	World Health Organization.WHO-global tuberculosis report 2014 [R]. Geneva:WHO,2014.
[7]	ZUMLA A,GEORGE A,SHARMA V,et al.WHO's 2013 global report on tuberculosis: successes,threats,and opportunities[J]. Lancet,2013,382(9907):1765-1767.
[8]	WALLIS R S,KIM P,COLE S,et al.Tuberculosis biomarkers discovery: developments,needs,and challenges[J]. Lancet Infect Dis,2013,13(4):362-372.
[9]	MAERTZDORF J,WEINER J 3rd,KAUFMANN S H. Enabling biomarkers for tuberculosis control[J]. Int J Tuberc Lung Dis,2012,16(9):1140-1148.
[10]	FENG X,XIU B,CHEN K,et al.Enhanced serodiagnostic utility of novel Mycobacterium tuberculosis polyproteins[J]. J Infect,2013,66(4):366-375.
[11]	LIU F,WU X,LI L,et al.Expression,purification and characterization of two truncated peste des petits ruminants virus matrix proteins in Escherichia coli,and production of polyclonal antibodies against this protein[J]. Protein Expr Purif,2013,91(1):1-9.
[12]	LI Q,YU H,ZHANG Y,et al.Immunogenicity and protective efficacy of a fusion protein vaccine consisting of antigen Ag85B and HspX against Mycobacterium tuberculosis infection in mice[J]. Scand J Immunol,2011,73(6):568-576.
[13]	周鹏,丁莹莹,林子玉,等. 结核分枝杆菌特异性蛋白片段RV3388和6种特异抗原在结核抗体检测中的应用价值[J]. 安徽医科大学学报,2015,50(10):1404-1409.
[14]	WHITWORTH W C,GOODWIN D J,RACSTER L,et al.Variability of the QuantiFERON®-TB gold in-tube test using automated and manual methods[J]. PLoS One,2014,9(1):e86721.

项目	临界值	敏感性（95%CI）（%）	特异性（95%CI）（%）	约登指数（95%CI）
COI₁	0.90	92.5（90.0~95.0）	82.1（78.8~85.4）	0.746（0.682~0.821）
COI₂	3.65	79.0（66.8~88.3）	62.1（48.4~74.5）	0.411（0.152~0.628）
Cut-off值	0.18	86.7（84.6~88.8）	83.9（70.9~86.9）	0.706（0.634~0.778）
项目	阳性似然比（95%CI）	阴性似然比（95%CI）	阳性预测值（95%CI）	阴性预测值（95%CI）
COI₁	5.180 （4.852~5.508）	0.217 （0.142~0.449）	0.787（0.720~0.855）	0.939（0.900~0.978）
COI₂	2.080（1.500~3.000）	0.340（0.200~0.600）	0.690（0.569~0.795）	0.735（0.589~0.851）
Cut-off值	5.393 （5.039~5.745）	0.191（0.114~0.402）	0.794（0.725~0.863）	0.898（0.851~0.945）

项目	临界值	敏感性（95%CI）（%）	特异性（95%CI）（%）	约登指数（95%CI）
COI₁	0.90	92.5（90.0~95.0）	82.1（78.8~85.4）	0.746（0.682~0.821）
COI₂	3.65	79.0（66.8~88.3）	62.1（48.4~74.5）	0.411（0.152~0.628）
Cut-off值	0.18	86.7（84.6~88.8）	83.9（70.9~86.9）	0.706（0.634~0.778）
项目	阳性似然比（95%CI）	阴性似然比（95%CI）	阳性预测值（95%CI）	阴性预测值（95%CI）
COI₁	5.180 （4.852~5.508）	0.217 （0.142~0.449）	0.787（0.720~0.855）	0.939（0.900~0.978）
COI₂	2.080（1.500~3.000）	0.340（0.200~0.600）	0.690（0.569~0.795）	0.735（0.589~0.851）
Cut-off值	5.393 （5.039~5.745）	0.191（0.114~0.402）	0.794（0.725~0.863）	0.898（0.851~0.945）

[1]	XIAO Xiumei, LIANG Chao, LIU Caihong, LI Xiaoguang. Comparison of SARS-CoV-2 neutralizing antibody and specific antibody determination results [J]. Laboratory Medicine, 2023, 38(4): 352-356.
[2]	HU Yan, SHEN Ge, LI Qiong, ZENG Ziyan, , YANG Gang, LI Ping, CHEN Yufeng, ZHANG Zhen, XIE Xiaobing. Roles of 2 SARS-CoV-2 antibody assays in the diagnosis of corona virus disease 2019 [J]. Laboratory Medicine, 2020, 35(12): 1294-1297.
[3]	WU Jun, LU Renquan, GUO Lin. Role of serum CgA determination for neuroendocrine neoplasma [J]. Laboratory Medicine, 2019, 34(2): 122-125.
[4]	YE Zhenxuan, YANG Biwei, ZHOU Wenjing, LIU Qiang, LI Hongmei, ZHANG Haiyan, REN Zhijing, ZHANG Hua. Screening of specific anti-mitochondrial antibody-M2 in 36 459 healthy subjects in Guiyang [J]. Laboratory Medicine, 2018, 33(3): 205-208.
[5]	ZHAO Yinxia, OU Meixian, QU Yi, LU Youli, ZHANG Meiwei, LI Shuijun. Determination of human serum ouabain by UPLC-MS/MS and methodology comparison [J]. Laboratory Medicine, 2018, 33(11): 1013-1016.
[6]	XIE Liangcai, FAN Wen, XU Lei, XU Rong, LIU Tianchun. False negative interference of RF on serum HBeAg by ELISA [J]. Laboratory Medicine, 2017, 32(9): 765-768.
[7]	LING Yingchun, ZHOU Yueqin, DUAN Di, HU Lingmin. Determination of central nervous system specific protein for senile dementia [J]. Laboratory Medicine, 2017, 32(11): 1021-1023.
[8]	YAN Jun, YANG Wei, ZHAI Shuanzhu, XUE Zhixin, YU Peng, ZHOU Zeqi. Preparation of polyclonal antibody and development of a competitive ELISA for fungal (1,3)-beta-D-glucan [J]. Laboratory Medicine, 2015, 30(9): 931-933.
[9]	SUN Lishan, WANG Mingdong, LU Liu, LIU Yingbing, LU Lin, GUO Jinhu, FAN Lieying. Establishment of an ELISA for the quantitative measuring of glucagon-like peptide 1 and the primary clinical application [J]. Laboratory Medicine, 2015, 30(8): 835-840.
[10]	MENG Cunren, TANG Jing, ZHANG Zhaoxia.. Analysis on repeatability and diagnostic threshold value of 2 ELISA systems for anti-HCV antibody determination [J]. Laboratory Medicine, 2015, 30(12): 1175-1180.
[11]	ZHANG Haiping, YAN Huiping, ZHANG Xin, ZHAO Dantong, MA Yinxue, SUN Limei, LI Zhuomin.. Automatic ELISA system for the detection of anti-mitochondrial M2 antibody and its clinical significance [J]. Laboratory Medicine, 2015, 30(12): 1234-1237.
[12]	TANG Jing, BAO Jianling, MENG Cunren, ZHANG Zhaoxia. Confirmation and analysis of the cut-off value in hepatitis C antibody determined by ELISA with receiver operating characteristic curve [J]. , 2014, 29(8): 826-830.
[13]	YU Hong，ZHU Wei，CUI Yangyang，QUE Jinya. The investigation of the retesting range of the TPAb sample detected by ELISA [J]. , 2013, 28(4): 312-314.
[14]	XIAO Jinhua，ZHU Huayan，WANG Yaping，PAN Yuhong，HUANG Xuan. Detection of peripheral blood high mobility group protein box-1 in patients with gastric cancer and its clinical significance [J]. , 2013, 28(4): 301-304.
[15]	ZHU Yuqing,HOU Yumin.. Investigation on the range and confirmation test of hepatitis B surface antigen determination by ELISA [J]. , 2013, 28(11): 1038-1039.