Serum anti-Mce1A immunoglobulin detection as a tool for differential diagnosis of tuberculosis and latent tuberculosis infection in children and adolescents

The objective: to analyze the expression of certain genes in the blood cells of children and adolescence to differentiate the active and latent phases of tuberculosis infection.Subjects and methods. Peripheral blood samples collected in 36 pediatric patients with latent tuberculosis infection and 24 patients aged 1 to 16 years undergoing in-patient treatment for pulmonary tuberculosis were tested. A modified method for isolating messenger RNA and reverse transcriptional polymerase chain reaction was used to identify the transcription of six genes selected for analysis.Results. In a comparative study of the expression values of six promising genes in blood cells in the study of two groups of children and adolescents with latent and active tuberculosis infection, it was found that the most differentiating feature for determining active tuberculosis infection was a significantly higher level of expression of PDCD1 gene encoding PD1 lymphocyte receptor. At the same time, the sensitivity to detect the active infection was found to be 95.8%, specificity – 94.4%, the accuracy of the positive prognosis of active tuberculosis infection was 93.3%.

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Mycobacterium tuberculosis latency-associated antigen Rv1733c SLP improves the accuracy of differential diagnosis of active tuberculosis and latent tuberculosis infection

10.21203/rs.3.rs-121733/v1 ◽

2020 ◽

Author(s):

Lifan Zhang ◽

Huimin Ma ◽

Shijun Wan ◽

Yueqiu Zhang ◽

Mengqiu Gao ◽

...

Keyword(s):

T Cells ◽

Differential Diagnosis ◽

Sensitivity And Specificity ◽

Latent Tuberculosis Infection ◽

Latent Tuberculosis ◽

Active Tuberculosis ◽

Tuberculosis Infection ◽

Control Group ◽

College Hospital ◽

Serial Test

Abstract Background The differential diagnosis of active tuberculosis(ATB) and latent tuberculosis infection(LTBI) is still challenging. The objective of the study was to evaluate the accuracy of the novel M. tuberculosis latency-associated antigens Rv1733c and Rv1733c SLP for differentiating ATB from LTBI. Methods A case-control study was designed to enroll pathogen-confirmed ATB cases admitted to the Peking Union Medical College Hospital and Beijing Chest Hospital, whereas those with LTBI were denoted as the control group. The Fluorescence-Immunospot (FluoroSpot) assay was used to detect the frequencies of IL-2-, IFN-γ-secreting T cells stimulated by the M. tuberculosis latency-associated antigens Rv1733c and Rv1733c SLP. The combination of the ESAT-6/CFP-10-Fluorospot test was evaluated with regard to the sensitivity, specificity, predictive value and likelihood ratio for the differential diagnosis of ATB and LTBI. Results A total of 20 pathogens-confirmed TB and 28 LTBI cases were included. The sensitivity and specificity of ESAT-6/CFP-10-FluoroSpot for the differential diagnosis of ATB and LTBI were 95% (95% CI, 75.13–99.87%) and 82.14% (95% CI, 63.11–93.94%), respectively. Following stimulation with Rv1733c and Rv1733c SLP, the maximum AUROC was 0.711 (95% CI, 0.566–0.856) as determined by the ROC curve, which was used to assess the frequency of single IL-2-secreting T cells stimulated by Rv1733c SLP. The cutoff value of 0 SFCs/2.5 × 105 PBMCs was used for the analysis. The frequency, sensitivity and specificity of Rv1733c SLP for differentiating ATB and LTBI were 75% (95% CI, 50.90–91.34%) and 60.71% (95% CI, 40.58–78.50%), respectively. The ESAT-6/cfp-10-fluorospot was combined with the frequency of single IL-2-secreting T cells, which were stimulated by Rv1733c SLP for the differential diagnosis of ATB and LTBI. This resulted in an increased sensitivity and specificity to 100% (95% CI, 83.16–100.00%), as determined by the parallel test and to 92.86% (95% CI, 71.77–97.73%) as determined by the serial test, respectively. Conclusions Rv1733c SLP has the potential to be used as a candidate antigen for T cell-based tuberculosis diagnostic tests, in combination with ESAT-6 and CFP-10, to differentiate between ATB and LTBI diagnosis.

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