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

Mycobacterium tuberculosis-derived circulating cell-free DNA in patients with pulmonary tuberculosis and persons with latent tuberculosis infection.
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DOI:
10.1371/journal.pone.0253879
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发表时间:
2021
期刊:
影响因子:
3.7
通讯作者:
Chen YM
Chen YM
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Pan SW;Su WJ;Chan YJ;Chuang FY;Feng JY;Chen YM

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肺结核(PTB)的及时诊断具有挑战性。虽然病原体来源的循环游离DNA (cfDNA)已在人类中检测到,但结核分枝杆菌(MTB) cfDNA检测在肺结核患者中的意义尚不清楚。本研究于2018年至2020年分别招募PTB患者和潜伏性结核感染(LTBI)患者作为研究组和对照组。我们测量了干扰素-γ水平并计算了血液单核细胞与淋巴细胞的比率(MLR)。我们对MTB的IS6110基因进行了血浆cfDNA提取、定量聚合酶链反应(qPCR)和微滴数字PCR。我们计算了使用MTB-cfDNA识别PTB的敏感性和特异性,并分析了与PTB诊断和MTB-cfDNA阳性相关的因素。我们招募了24例PTB患者和57例LTBI对照。MTB-cfDNA检测PTB的敏感性为54.2%(13/24),涂片阴性病例为46.2%(6/13)。两名LTBI对照组(3.5%)检测MTB-cfDNA阳性,特异性为96.5%(55/57)。以MTB-cfDNA阳性和MLR≥0.42鉴别PTB,敏感性提高到79.2%(19/24)。在肺结核患者中,MTB-cfDNA阳性患者的mtb特异性干扰素γ水平高于阴性患者(7.0±2.7 vs 2.7±3.0 IU/mL, p<0.001)。抗结核治疗2个月后MTB-cfDNA水平下降(p<0.001)。使用MTB-cfDNA识别PTB的敏感性为54.2%,在MLR≥0.42纳入分析后增加到79.2%。MTB-cfDNA阳性与mtb特异性免疫反应相关,治疗后MTB-cfDNA水平下降。MTB-cfDNA在肺结核治疗中的临床价值有待进一步研究。
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-γ 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 ≥0.42 to identify PTB, sensitivity increased to 79.2%(19/24). Among patients with PTB, MTB-specific interferon-γ 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<0.001). MTB-cfDNA levels declined after 2 months of anti-tuberculosis therapy (p<0.001). The sensitivity of using MTB-cfDNA to identify PTB in participants was 54.2%, which increased to 79.2% after incorporating an MLR ≥0.42 into the analysis. MTB-cfDNA positivity was associated with MTB-specific immune response, and MTB-cfDNA levels declined after treatment. The clinical value of MTB-cfDNA in PTB management necessitates further investigation.
通过液滴数字 PCR 检测循环结核分枝杆菌特异性 DNA,用于受攻击猴子的疫苗评估和结核病诊断
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影响因子: 13.2
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发表时间: 2013-06-01
期刊: CLINICAL CHEMISTRY
影响因子: 9.3
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发表时间: 2019-03
期刊: International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases
影响因子: --
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