Circulating mitochondrial cell-free DNA dynamics in patients with mycobacterial pulmonary infections: Potential for a novel biomarker of disease.
Circulating mitochondrial cell-free DNA dynamics in patients with mycobacterial pulmonary infections: Potential for a novel biomarker of disease.
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DOI：
10.3389/fimmu.2022.1040947
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发表时间：
2022
影响因子：
7.3
通讯作者：
Rodwell, Timothy C.
中科院分区：
文献类型：
--
作者：
Pan, Sheng-Wei;Syed, Rehan R.;Catanzaro, Donald G.;Ho, Mei-Lin;Shu, Chin-Chung;Tsai, Tsung-Yeh;Tseng, Yen-Han;Feng, Jia-Yih;Chen, Yuh-Min;Su, Wei-Juin;Catanzaro, Antonino;Rodwell, Timothy C.
人线粒体无细胞DNA（Mt-cfDNA）可以作为感染过程的有用生物标志物。我们研究了肺部分枝杆菌感染患者的Mt-cfDNA动力学，以确定这种新型生物标志物是否可用于区分疾病状态和严重程度。2018年6月至2021年8月期间，在台湾的一家三级医院入组了肺结核（PTB）、潜伏性结核感染（LTBI）和非结核分枝杆菌肺病（NTM-LD）患者。通过定量聚合酶链反应估计人Mt-cfDNA和核-cfDNA（Nu-cfDNA）拷贝数。与PTB和2个月痰培养阳性相关的变量，表明治疗反应差，使用logistic回归进行评估。在97名PTB患者、64名LTBI患者和51名NTM-LD患者中，PTB患者的Mt-cfDNA水平高于LTBI（p=0.001）或NTM-LD（p=0.006）。在结核分枝杆菌感染人群中，Mt-cfDNA水平在涂片阳性PTB患者中最高，其次是涂片阴性PTB（p<0.001），在LTBI人群中最低（p=0.009）。高于中位数的Mt-cfDNA（而非Nu-cfDNA）水平有助于区分培养阳性PTB与培养阴性PTB和LTBI（调整后OR 2.430 [95% CI 1.139-5.186]，p=0.022），并有助于区分PTB与NTM-LD（调整后OR 4.007 [1.382-12.031]，p=0.011）。PTB患者治疗2个月后Mt-cfDNA水平降低（p=0.010）。临界Mt-cfDNA水平大于62.62 x 106拷贝/μ L血浆与2个月培养阳性的10倍风险相关（校正OR 9.691 [1.046-89.813]，p=0.046）。在PTB患者中，升高的Mt-cfDNA水平与PTB疾病和2个月时痰转化失败相关，并且在治疗后降低。
Human mitochondrial cell-free DNA (Mt-cfDNA) may serve as a useful biomarker for infectious processes. We investigated Mt-cfDNA dynamics in patients with pulmonary mycobacterial infections to determine if this novel biomarker could be used to differentiate disease states and severity. Patients with pulmonary tuberculosis (PTB), latent tuberculosis infection (LTBI), and nontuberculous mycobacterial-lung disease (NTM-LD) were enrolled at a tertiary care hospital in Taiwan between June 2018 and August 2021. Human Mt-cfDNA and nuclear-cfDNA (Nu-cfDNA) copy numbers were estimated by quantitative polymerase chain reaction. Variables associated with PTB and 2-month sputum culture-positivity, indicating poor treatment response, were assessed using logistic regression. Among 97 patients with PTB, 64 with LTBI, and 51 with NTM-LD, Mt-cfDNA levels were higher in patients with PTB than in LTBI (p=0.001) or NTM-LD (p=0.006). In the Mycobacterium tuberculosis-infected population, Mt-cfDNA levels were highest in smear-positive PTB patients, followed by smear-negative PTB (p<0.001), and were lowest in LTBI persons (p=0.009). A Mt-cfDNA, but not Nu-cfDNA, level higher than the median helped differentiate culture-positive PTB from culture-negative PTB and LTBI (adjusted OR 2.430 [95% CI 1.139–5.186], p=0.022) and differentiate PTB from NTM-LD (adjusted OR 4.007 [1.382–12.031], p=0.011). Mt-cfDNA levels decreased after 2 months of treatment in PTB patients (p=0.010). A cutoff Mt-cfDNA level greater than 62.62 x 106 copies/μL-plasma was associated with a 10-fold risk of 2-month culture-positivity (adjusted OR 9.691 [1.046–89.813], p=0.046). Elevated Mt-cfDNA levels were associated with PTB disease and failed sputum conversion at 2 months in PTB patients, and decreased after treatment.
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影响因子：
7.3
作者：
Carranza C;Pedraza-Sanchez S;de Oyarzabal-Mendez E;Torres M
通讯作者：
Torres M
影响因子：
8.8
作者：
Olson GS;Murray TA;Jahn AN;Mai D;Diercks AH;Gold ES;Aderem A
通讯作者：
Aderem A
影响因子：
17.1
作者：
De Vlaminck I;Valantine HA;Snyder TM;Strehl C;Cohen G;Luikart H;Neff NF;Okamoto J;Bernstein D;Weisshaar D;Quake SR;Khush KK
通讯作者：
Khush KK
影响因子：
3.7
作者：
Pan SW;Su WJ;Chan YJ;Chuang FY;Feng JY;Chen YM
通讯作者：
Chen YM
DOI：
10.1097/qai.0000000000001893
发表时间：
2019-02-01
期刊：
Journal of acquired immune deficiency syndromes (1999)
影响因子：
--
作者：
Choudhary RK;Wall KM;Njuguna I;Pavlinac PB;LaCourse SM;Otieno V;Gatimu J;Stern J;Maleche-Obimbo E;Wamalwa D;John-Stewart G;Cranmer LM
通讯作者：
Cranmer LM