Circulating mitochondrial cell-free DNA dynamics in patients with mycobacterial pulmonary infections: Potential for a novel biomarker of disease

• Published in: Frontiers in immunology 2022-11, Vol.13, p.1040947-1040947
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: biomarker; Biomarkers; cell-free DNA; Cell-Free Nucleic Acids - genetics; Humans; Immunology; Latent Tuberculosis - diagnosis; Latent Tuberculosis - genetics; mitochondria; Mitochondrial Dynamics; Mycobacterium Infections, Nontuberculous - diagnosis; Pneumonia; pulmonary tuberculosis; treatment response monitoring; Tuberculosis, Pulmonary - diagnosis; Tuberculosis, Pulmonary - drug therapy; Tuberculosis, Pulmonary - genetics
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2022.1040947

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 -infected population, Mt-cfDNA levels were highest in smear-positive PTB patients, followed by smear-negative PTB (p