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

IF 2.8 3区医学 Q3 IMMUNOLOGY Tuberculosis Pub Date : 2025-01-21 DOI:10.1016/j.tube.2025.102611

Lauma Freimane , Agnija Kivrāne , Viktorija Ulanova , Anda Vīksna , Eduards Sevostjanovs , Solveiga Grīnberga , Andra Cīrule , Alvils Krams , Renāte Ranka

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Abstract

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.

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有关抗结核（TB）化疗对全身反应影响的生物标志物研究仍然有限。在这项研究中，我们旨在调查药物易感肺结核（DS-TB）患者血浆中循环游离细胞线粒体 DNA（ccf-mtDNA）和循环游离细胞核 DNA（ccf-nDNA）拷贝数（CN）的波动，并解读与这些波动相关的因素。结果显示，服药前、服药后 2 小时和 6 小时血浆样本中的ccf-mtDNA CN 发生了很大变化，每个时间点的患者间差异很大。多变量线性回归显示，ccf-mtDNA CN 的动态受患者年龄、乙胺丁醇药代动力学和体重指数（BMI）的影响；乙胺丁醇暴露是最重要的因素。在所有三个时间点均观察到极低的ccf-nDNA CN，且差异很小；没有任何因素与ccf-nDNA密切相关。总之，我们的研究揭示了抗结核化疗、年龄和体重指数对血浆中循环ccf-mtDNA CN 急性变化的影响，并强调了乙胺丁醇对结核病患者线粒体的系统相关影响。要了解ccf-DNA在肺结核患者中的生物学相关性并验证其在肺结核治疗监测中的应用，还需要进行更大规模的队列研究。

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来源期刊

Tuberculosis 医学-呼吸系统

CiteScore

4.60

自引率

3.10%

发文量

审稿时长

49 days

期刊介绍： Tuberculosis is a speciality journal focusing on basic experimental research on tuberculosis, notably on bacteriological, immunological and pathogenesis aspects of the disease. The journal publishes original research and reviews on the host response and immunology of tuberculosis and the molecular biology, genetics and physiology of the organism, however discourages submissions with a meta-analytical focus (for example, articles based on searches of published articles in public electronic databases, especially where there is lack of evidence of the personal involvement of authors in the generation of such material). We do not publish Clinical Case-Studies. Areas on which submissions are welcomed include: -Clinical TrialsDiagnostics- Antimicrobial resistance- Immunology- Leprosy- Microbiology, including microbial physiology- Molecular epidemiology- Non-tuberculous Mycobacteria- Pathogenesis- Pathology- Vaccine development. This Journal does not accept case-reports. The resurgence of interest in tuberculosis has accelerated the pace of relevant research and Tuberculosis has grown with it, as the only journal dedicated to experimental biomedical research in tuberculosis.