TY - JOUR
T1 - Circulating mitochondrial cell-free DNA dynamics in patients with mycobacterial pulmonary infections
T2 - Potential for a novel biomarker of disease
AU - Pan, Sheng Wei
AU - Syed, Rehan R.
AU - Catanzaro, Donald G.
AU - Ho, Mei Lin
AU - Shu, Chin Chung
AU - Tsai, Tsung Yeh
AU - Tseng, Yen Han
AU - Feng, Jia Yih
AU - Chen, Yuh Min
AU - Su, Wei Juin
AU - Catanzaro, Antonino
AU - Rodwell, Timothy C.
N1 - Funding Information:
S-WP was funded by grants from Taipei Veterans General Hospital [V110C-040] and the Ministry of Science and Technology [107-2314-B-075-057, 108-2314-B-075-001, 109-2314-B-075-094, 110-2314-B-075-077, 111-2314-B-075-059] in Taiwan. TR, DC and AC were funded by NIH NIAID grant # R01AI137681.
Publisher Copyright:
Copyright © 2022 Pan, Syed, Catanzaro, Ho, Shu, Tsai, Tseng, Feng, Chen, Su, Catanzaro and Rodwell.
PY - 2022/11
Y1 - 2022/11
N2 - Objectives: 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. Methods: 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. Results: 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). Conclusion: Elevated Mt-cfDNA levels were associated with PTB disease and failed sputum conversion at 2 months in PTB patients, and decreased after treatment.
AB - Objectives: 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. Methods: 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. Results: 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). Conclusion: Elevated Mt-cfDNA levels were associated with PTB disease and failed sputum conversion at 2 months in PTB patients, and decreased after treatment.
KW - biomarker
KW - cell-free DNA
KW - mitochondria
KW - pulmonary tuberculosis
KW - treatment response monitoring
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UR - http://www.scopus.com/inward/citedby.url?scp=85143217044&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2022.1040947
DO - 10.3389/fimmu.2022.1040947
M3 - Article
C2 - 36466831
AN - SCOPUS:85143217044
SN - 1664-3224
VL - 13
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 1040947
ER -
