TY - JOUR
T1 - Fluctuations in circulating cell-free mitochondrial and nuclear DNA copy numbers in blood plasma after anti-tuberculosis drug intake in patients with drug-susceptible tuberculosis
AU - Freimane, Lauma
AU - Kivrāne, Agnija
AU - Ulanova, Viktorija
AU - Vīksna, Anda
AU - Sevostjanovs, Eduards
AU - Grīnberga, Solveiga
AU - Cīrule, Andra
AU - Krams, Alvils
AU - Ranka, Renāte
N1 - Publisher Copyright:
© 2025 The Authors
PY - 2025/3
Y1 - 2025/3
N2 - Biomarker research characterising the effect of anti-tuberculosis (TB) chemotherapy on systemic body response is still limited. In this study, we aimed to investigate fluctuations in circulating cell-free mitochondrial DNA (ccf-mtDNA) and circulating cell-free nuclear DNA (ccf-nDNA) copy number (CN) in blood plasma of patients with drug-susceptible TB (DS-TB) and to decipher factors related to these fluctuations. The results showed considerable changes in ccf-mtDNA CN in plasma samples before drug intake and 2 and 6 h afterwards, with high inter patient variability at each time point. Multivariate linear regression revealed that the dynamics of ccf-mtDNA CN was influenced by patients' age, ethambutol pharmacokinetics, and body-mass index (BMI); ethambutol exposure emerged as the most significant factor. Very low ccf-nDNA CN in all three time points with little variation was observed; none factors were strongly associated with ccf-nDNA. In conclusion, our study revealed the effect of anti-TB chemotherapy, age and BMI on acute changes in circulating ccf-mtDNA CN in blood plasma and highlighted the systemic, mitochondria-related effects of ethambutol in patients with TB. Further studies with larger cohorts are needed to understand the biological relevance of ccf-DNA in patients with TB and to validate its application in TB treatment monitoring.
AB - Biomarker research characterising the effect of anti-tuberculosis (TB) chemotherapy on systemic body response is still limited. In this study, we aimed to investigate fluctuations in circulating cell-free mitochondrial DNA (ccf-mtDNA) and circulating cell-free nuclear DNA (ccf-nDNA) copy number (CN) in blood plasma of patients with drug-susceptible TB (DS-TB) and to decipher factors related to these fluctuations. The results showed considerable changes in ccf-mtDNA CN in plasma samples before drug intake and 2 and 6 h afterwards, with high inter patient variability at each time point. Multivariate linear regression revealed that the dynamics of ccf-mtDNA CN was influenced by patients' age, ethambutol pharmacokinetics, and body-mass index (BMI); ethambutol exposure emerged as the most significant factor. Very low ccf-nDNA CN in all three time points with little variation was observed; none factors were strongly associated with ccf-nDNA. In conclusion, our study revealed the effect of anti-TB chemotherapy, age and BMI on acute changes in circulating ccf-mtDNA CN in blood plasma and highlighted the systemic, mitochondria-related effects of ethambutol in patients with TB. Further studies with larger cohorts are needed to understand the biological relevance of ccf-DNA in patients with TB and to validate its application in TB treatment monitoring.
KW - Circulating cell-free mitochondrial DNA
KW - Circulating cell-free nuclear DNA
KW - Medication effects
KW - Pharmacokinetics
KW - Tuberculosis
UR - https://pubmed.ncbi.nlm.nih.gov/39862444/
UR - http://www.scopus.com/inward/record.url?scp=85215835268&partnerID=8YFLogxK
U2 - 10.1016/j.tube.2025.102611
DO - 10.1016/j.tube.2025.102611
M3 - Article
C2 - 39862444
SN - 1472-9792
VL - 151
JO - Tuberculosis
JF - Tuberculosis
M1 - 102611
ER -
