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Evaluation of IFIT3 and ORM1 as Biomarkers for Discriminating Active Tuberculosis from Latent Infection

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Abstract

Objective

Current commercially available immunological tests cannot be used for discriminating active tuberculosis (TB) from latent TB infection. To evaluate the value of biomarker candidates in the diagnosis of active TB, this study aimed to identify differentially expressed genes in peripheral blood mononuclear cells (PBMCs) between patients with active TB and individuals with latent TB infection by transcriptome sequencing.

Methods

The differentially expressed genes in unstimulated PBMCs and in Mycobacterium tuberculosis (Mtb) antigen-stimulated PBMCs from patients with active TB and individuals with latent TB infection were identified by transcriptome sequencing. Selected candidate genes were evaluated in cohorts consisting of 110 patients with TB, 30 individuals with latent TB infections, and 50 healthy controls by quantitative real-time RT-PCR. Receiver operating characteristic (ROC) curve analysis was performed to calculate the diagnostic value of the biomarker candidates.

Results

Among the differentially expressed genes in PBMCs without Mtb antigen stimulation, interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) had the highest area under curve (AUC) value (0.918, 95% CI: 0.852–0.984, P<0.0001) in discriminating patients with active TB from individuals with latent TB infection, with a sensitivity of 91.86% and a specificity of 84.00%. In Mtb antigen-stimulated PBMCs, orosomucoid 1 (ORM1) had a high AUC value (0.833, 95% CI: 0.752–0.915, P<0.0001), with a sensitivity of 81.94% and a specificity of 70.00%.

Conclusion

IFIT3 and ORM1 might be potential biomarkers for discriminating active TB from latent TB infection.

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Author notes

  1. These authors contributed equally to this work.

Authors and Affiliations

  1. Tuberculosis Prevention and Control Key Laboratory, Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Institute of Senior Department of Tuberculosis, the Eighth Medical Center of Chinese PLA General Hospital, Beijing, 100091, China

    Bing-fen Yang, Fei Zhai, Zhi-hong Cao, Yan-hua Liu, Ruo Wang & Xiao-xing Cheng

  2. Fourth Division, Senior Department of Tuberculosis, the Eighth Medical Center of PLA General Hospital, Beijing, 100091, China

    Shan Yu

  3. Department of Tuberculosis Prevention and Control, Senior Department of Tuberculosis, the Eighth Medical Center of PLA General Hospital, Beijing, 100091, China

    Hong-juan An

Authors
  1. Bing-fen Yang
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  2. Fei Zhai
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  3. Shan Yu
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  4. Hong-juan An
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  5. Zhi-hong Cao
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  6. Yan-hua Liu
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Corresponding author

Correspondence to Xiao-xing Cheng.

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The authors declare no conflicts of interest.

Additional information

This work was supported by grants from the Thirteen-Fifth Mega-Scientific Project on “Prevention and Treatment of AIDS, Viral Hepatitis and Other Infectious Diseases” (No. 2017ZX10201301-007-002) and the National Natural Science Foundation of China (No. 82072233).

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Yang, Bf., Zhai, F., Yu, S. et al. Evaluation of IFIT3 and ORM1 as Biomarkers for Discriminating Active Tuberculosis from Latent Infection. CURR MED SCI 42, 1201–1212 (2022). https://doi.org/10.1007/s11596-022-2649-6

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  • DOI: https://doi.org/10.1007/s11596-022-2649-6

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