Circulating mitochondrial cell-free DNA dynamics in patients with mycobacterial pulmonary infections: Potential for a novel biomarker of disease
ObjectivesHuman 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.Metho...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1040947/full |
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| author | Sheng-Wei Pan Sheng-Wei Pan Sheng-Wei Pan Rehan R. Syed Donald G. Catanzaro Mei-Lin Ho Mei-Lin Ho Chin-Chung Shu Chin-Chung Shu Tsung-Yeh Tsai Tsung-Yeh Tsai Yen-Han Tseng Yen-Han Tseng Jia-Yih Feng Jia-Yih Feng Yuh-Min Chen Yuh-Min Chen Wei-Juin Su Antonino Catanzaro Timothy C. Rodwell |
| author_facet | Sheng-Wei Pan Sheng-Wei Pan Sheng-Wei Pan Rehan R. Syed Donald G. Catanzaro Mei-Lin Ho Mei-Lin Ho Chin-Chung Shu Chin-Chung Shu Tsung-Yeh Tsai Tsung-Yeh Tsai Yen-Han Tseng Yen-Han Tseng Jia-Yih Feng Jia-Yih Feng Yuh-Min Chen Yuh-Min Chen Wei-Juin Su Antonino Catanzaro Timothy C. Rodwell |
| author_sort | Sheng-Wei Pan |
| collection | DOAJ |
| description | ObjectivesHuman 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.MethodsPatients 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.ResultsAmong 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).ConclusionElevated Mt-cfDNA levels were associated with PTB disease and failed sputum conversion at 2 months in PTB patients, and decreased after treatment. |
| first_indexed | 2024-04-11T16:03:50Z |
| format | Article |
| id | doaj.art-8fc2df74f932474c8054c6fa3b1cd66a |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T16:03:50Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-8fc2df74f932474c8054c6fa3b1cd66a2022-12-22T04:14:53ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-11-011310.3389/fimmu.2022.10409471040947Circulating mitochondrial cell-free DNA dynamics in patients with mycobacterial pulmonary infections: Potential for a novel biomarker of diseaseSheng-Wei Pan0Sheng-Wei Pan1Sheng-Wei Pan2Rehan R. Syed3Donald G. Catanzaro4Mei-Lin Ho5Mei-Lin Ho6Chin-Chung Shu7Chin-Chung Shu8Tsung-Yeh Tsai9Tsung-Yeh Tsai10Yen-Han Tseng11Yen-Han Tseng12Jia-Yih Feng13Jia-Yih Feng14Yuh-Min Chen15Yuh-Min Chen16Wei-Juin Su17Antonino Catanzaro18Timothy C. Rodwell19Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, TaiwanSchool of Medicine, National Yang Ming Chiao Tung University, Taipei, TaiwanDivision of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California San Diego, La Jolla, CA, United StatesDivision of Infectious Diseases and Global Public Health, University of California San Diego, La Jolla, CA, United StatesDepartment of Biological Sciences, University of Arkansas, Fayetteville, AR, United StatesDepartment of Chemistry, Soochow University, Taipei, TaiwanDepartment of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA, United StatesDepartment of Internal Medicine, National Taiwan University Hospital, Taipei, TaiwanCollege of Medicine, National Taiwan University, Taipei, TaiwanDepartment of Chest Medicine, Taipei Veterans General Hospital, Taipei, TaiwanSchool of Medicine, National Yang Ming Chiao Tung University, Taipei, TaiwanDepartment of Chest Medicine, Taipei Veterans General Hospital, Taipei, TaiwanSchool of Medicine, National Yang Ming Chiao Tung University, Taipei, TaiwanDepartment of Chest Medicine, Taipei Veterans General Hospital, Taipei, TaiwanSchool of Medicine, National Yang Ming Chiao Tung University, Taipei, TaiwanDepartment of Chest Medicine, Taipei Veterans General Hospital, Taipei, TaiwanSchool of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan0Division of Chest Medicine, China Medical University Hospital, Taipei Branch, Taipei, TaiwanDivision of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California San Diego, La Jolla, CA, United StatesDivision of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California San Diego, La Jolla, CA, United StatesObjectivesHuman 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.MethodsPatients 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.ResultsAmong 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).ConclusionElevated Mt-cfDNA levels were associated with PTB disease and failed sputum conversion at 2 months in PTB patients, and decreased after treatment.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1040947/fullcell-free DNAmitochondriapulmonary tuberculosistreatment response monitoringbiomarker |
| spellingShingle | Sheng-Wei Pan Sheng-Wei Pan Sheng-Wei Pan Rehan R. Syed Donald G. Catanzaro Mei-Lin Ho Mei-Lin Ho Chin-Chung Shu Chin-Chung Shu Tsung-Yeh Tsai Tsung-Yeh Tsai Yen-Han Tseng Yen-Han Tseng Jia-Yih Feng Jia-Yih Feng Yuh-Min Chen Yuh-Min Chen Wei-Juin Su Antonino Catanzaro Timothy C. Rodwell Circulating mitochondrial cell-free DNA dynamics in patients with mycobacterial pulmonary infections: Potential for a novel biomarker of disease Frontiers in Immunology cell-free DNA mitochondria pulmonary tuberculosis treatment response monitoring biomarker |
| title | Circulating mitochondrial cell-free DNA dynamics in patients with mycobacterial pulmonary infections: Potential for a novel biomarker of disease |
| title_full | Circulating mitochondrial cell-free DNA dynamics in patients with mycobacterial pulmonary infections: Potential for a novel biomarker of disease |
| title_fullStr | Circulating mitochondrial cell-free DNA dynamics in patients with mycobacterial pulmonary infections: Potential for a novel biomarker of disease |
| title_full_unstemmed | Circulating mitochondrial cell-free DNA dynamics in patients with mycobacterial pulmonary infections: Potential for a novel biomarker of disease |
| title_short | Circulating mitochondrial cell-free DNA dynamics in patients with mycobacterial pulmonary infections: Potential for a novel biomarker of disease |
| title_sort | circulating mitochondrial cell free dna dynamics in patients with mycobacterial pulmonary infections potential for a novel biomarker of disease |
| topic | cell-free DNA mitochondria pulmonary tuberculosis treatment response monitoring biomarker |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1040947/full |
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