Mycobacterium tuberculosis–derived circulating cell-free DNA in patients with pulmonary tuberculosis and persons with latent tuberculosis infection

The timely diagnosis of pulmonary tuberculosis (PTB) is challenging. Although pathogen-derived circulating cell-free DNA (cfDNA) has been detected in humans, the significance of Mycobacterium tuberculosis (MTB)-cfDNA detection in patients with PTB remains unclear. This study enrolled patients with P...

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Bibliographic Details
Published in:PloS one 2021-06, Vol.16 (6), p.e0253879-e0253879
Main Authors: Pan, Sheng-Wei, Su, Wei-Juin, Chan, Yu-Jiun, Chuang, Fan-Yi, Feng, Jia-Yih, Chen, Yuh-Min
Format: Article
Language:English
Subjects:
Biology and Life Sciences
Deoxyribonucleic acid
Diagnosis
DNA
Genetic aspects
Hospitals
Immune response
Infections
Infectious diseases
Interferon
Lymphocytes
Mathematical analysis
Medical diagnosis
Medicine
Medicine and Health Sciences
Monocytes
Mycobacterium tuberculosis
Patients
Plasma
Polymerase chain reaction
Public health
Pulmonary tuberculosis
Research and Analysis Methods
Tuberculosis
γ-Interferon
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Summary:The timely diagnosis of pulmonary tuberculosis (PTB) is challenging. Although pathogen-derived circulating cell-free DNA (cfDNA) has been detected in humans, the significance of Mycobacterium tuberculosis (MTB)-cfDNA detection in patients with PTB remains unclear. This study enrolled patients with PTB and persons with latent tuberculosis infection (LTBI) as the study and control groups, respectively, from 2018 to 2020. We measured interferon-[gamma] levels and calculated blood monocyte-to-lymphocyte ratio (MLR). We conducted plasma cfDNA extraction, quantitative polymerase chain reaction (qPCR), and droplet digital PCR targeting the IS6110 gene of MTB. We calculated the sensitivity and specificity of using MTB-cfDNA to identify PTB and analyzed the factors associated with PTB diagnosis and MTB-cfDNA positivity. We enrolled 24 patients with PTB and 57 LTBI controls. The sensitivity of using MTB-cfDNA to identify PTB was 54.2%(13/24) in total and 46.2%(6/13) in smear-negative cases. Two LTBI controls (3.5%) tested positive for MTB-cfDNA, indicating a specificity of 96.5%(55/57). By using MTB-cfDNA positivity and an MLR [greater than or equal to]0.42 to identify PTB, sensitivity increased to 79.2%(19/24). Among patients with PTB, MTB-specific interferon-[gamma] levels were higher in MTB-cfDNA positive participants than in those who tested negative (7.0 ±2.7 vs 2.7±3.0 IU/mL, p
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0253879